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WARNING: SECONDARY EXPOSURE TO TESTOSTERONE WARNING: SECONDARY EXPOSURE TO TESTOSTERONE See full prescribing information for complete boxed warning. Virilization has been reported in children who were secondarily exposed to testosterone gel ( 5.1 , 6.2 ). Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel ( 2.2 , 5.1 ). Healthcare providers should advise patients to strictly adhere to recommended instructions for use ( 2.2 , 5.1 , 17 ). Virilization has been reported in children who were secondarily exposed to testosterone gel [see WARNINGS AND PRECAUTIONS ( 5.1 ) and ADVERSE REACTIONS ( 6.2 )] . Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel [see DOSAGE AND ADMINISTRATION ( 2.2 ) and WARNINGS AND PRECAUTIONS ( 5.1 )] . Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see DOSAGE AND ADMINISTRATION ( 2.2 ), WARNINGS AND PRECAUTIONS ( 5.1 ) and PATIENT COUNSELING INFORMATION ( 17 )] .

RECENT MAJOR CHANGES Warnings and Precautions, Venous Thromboembolism ( 5.3 ) 07/2025 Warnings and Precautions, Blood Pressure Increases ( 5.5 ) 07/2025 Warnings and Precautions, Cardiovascular Risk ( 5.5 ) Removed 07/2025

1 INDICATIONS AND USAGE Testosterone gel 1.62% is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired) ( 1 ) Hypogonadotropic hypogonadism (congenital or acquired) ( 1 ) Limitations of use: Safety and efficacy of testosterone gel 1.62% in men with "age-related hypogonadism" have not been established. ( 1 ) Safety and efficacy of testosterone gel 1.62% in males less than 18 years old have not been established. ( 1 , 8.4 ) Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure. ( 1 , 12.3 ) Testosterone gel 1.62% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range. Limitations of use: Safety and efficacy of testosterone gel 1.62% in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established. Safety and efficacy of testosterone gel 1.62% in males less than 18 years old have not been established [see USE IN SPECIFIC POPULATIONS ( 8.4 )] . Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see INDICATIONS AND USAGE ( 1 ), and CLINICAL PHARMACOLOGY ( 12.3 )] .

2 DOSAGE AND ADMINISTRATION Dosage and Administration for testosterone gel 1.62% differs from testosterone gel 1%. For dosage and administration of testosterone gel 1% refer to its full prescribing information. ( 2 ) Prior to initiating testosterone gel 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range ( 2 ). Starting dose of testosterone gel 1.62% is 40.5 mg of testosterone (2 pump actuations), applied topically once daily in the morning. ( 2.1 ) Apply to clean, dry, intact skin of the shoulders and upper arms. Do not apply testosterone gel 1.62% to any other parts of the body including the abdomen, genitals, chest, armpits (axillae), or knees. ( 2.2 , 12.3 ) Dose adjustment: Testosterone Gel 1.62% can be dose adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation) and a maximum of 81 mg of testosterone (4 pump actuations). The dose should be titrated based on the pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment or following dose adjustment. Additionally, serum testosterone concentration should be assessed periodically thereafter. ( 2.1 ) Patients should wash hands immediately with soap and water after applying testosterone gel 1.62% and cover the application site(s) with clothing after the gel has dried. Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated. ( 2.2 ) Dosage and Administration for testosterone gel 1.62% differs from testosterone gel 1%. For dosage and administration of testosterone gel 1% refer to its full prescribing information. ( 2 ) Prior to initiating testosterone gel 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. 2.1 Dosing and Dose Adjustment The recommended starting dose of testosterone gel 1.62% is 40.5 mg of testosterone (2 pump actuations) applied topically once daily in the morning to the shoulders and upper arms. The dose can be adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation) and a maximum of 81 mg of testosterone (4 pump actuations). To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step. Table 1: Dose Adjustment Criteria Pre - Dose Morning Total Serum Testosterone Concentration Dose Titration Greater than 750 ng/dL Decrease daily dose by 20.25 mg (1 pump actuation) Equal to or greater than 350 and equal to or less than 750 ng/dL No change: continue on current dose Less than 350 ng/dL Increase daily dose by 20.25 mg (1 pump actuation) The application site and dose of testosterone gel 1.62% are not substitutable-with other topical testosterone products. 2.2 Administration Instructions Testosterone gel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders.

s than 350 ng/dL Increase daily dose by 20.25 mg (1 pump actuation) The application site and dose of testosterone gel 1.62% are not substitutable-with other topical testosterone products. 2.2 Administration Instructions Testosterone gel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply testosterone gel 1.62% to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees [see CLINICAL PHARMACOLOGY ( 12.3 )] . Area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply testosterone gel 1.62% and spread across the maximum surface area as directed in Table 2 (for pump) and in Figure 1. Table 2: Application Sites for Testosterone Gel 1.62%, Pump Total Dose of Testosterone Total Pump Actuations Pump Actuations Per Upper Arm and Shoulder Upper Arm and Shoulder # 1 Upper Arm and Shoulder # 2 20.25 mg 1 1 0 40.5 mg 2 1 1 60.75 mg 3 2 1 81 mg 4 2 2 The prescribed daily dose of testosterone gel 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1. Figure 1. Application Sites for Testosterone Gel 1.62% Once the application site is dry, the site should be covered with clothing [see CLINICAL PHARMACOLOGY ( 12.3 )] . Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including testosterone gel 1.62%, are flammable. The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see CLINICAL PHARMACOLOGY ( 12.3 )] . To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose. After the priming procedure, fully depress the actuator once for every 20.25 mg of testosterone gel 1.62%. Testosterone gel 1.62% should be delivered directly into the palm of the hand and then applied to the application sites. Alternatively, testosterone gel 1.62% can be applied directly to the application sites from the pump. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from testosterone gel 1.62%-treated skin: Children and women should avoid contact with unwashed or unclothed application site(s) of men using testosterone gel 1.62%. Testosterone gel 1.62% should only be applied to the upper arms and shoulders. The area of application should be limited to the area that will be covered by a short sleeve t-shirt. Patients should wash their hands with soap and water immediately after applying testosterone gel 1.62%. Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried. Prior to situations in which direct skin-to-skin contact is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue. In the event that unwashed or unclothed skin to which testosterone gel 1.62% has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible. Figure 1 a Figure 1 b

3 DOSAGE FORMS AND STRENGTHS Testosterone gel 1.62% for topical use is available as follows: a metered-dose pump that delivers 20.25 mg testosterone per actuation. ( 3 ) Testosterone gel 1.62% for topical use only, is available as follows: A metered-dose pump. Each pump actuation delivers 20.25 mg of testosterone in 1.25 g of gel.

4 CONTRAINDICATIONS Men with carcinoma of the breast or known or suspected prostate cancer ( 4 , 5.1 ) Women who are pregnant. Testosterone may cause fetal harm ( 4 , 8.1 ) Testosterone gel 1.62% is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see WARNINGS AND PRECAUTIONS ( 5.4 ) and ADVERSE REACTIONS ( 6.1 )]. Testosterone gel 1.62% is contraindicated in women who are pregnant. Testosterone gel 1.62% can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women need to be aware of the potential for transfer of testosterone from men treated with testosterone gel 1.62%. If a pregnant woman is exposed to testosterone gel 1.62%, she should be apprised of the potential hazard to the fetus [see WARNINGS AND PRECAUTIONS ( 5.1 ) and USE IN SPECIFIC POPULATIONS ( 8.1 )] .

5 WARNINGS AND PRECAUTIONS Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer: Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH ( 5.4 ) Potential for Secondary Exposure to Testosterone: Avoid unintentional exposure of women or children to testosterone gel 1.62%. Secondary exposure to testosterone can produce signs of virilization. Testosterone gel 1.62% should be discontinued until the cause of virilization is identified ( 5.1 ) Venous Thromboembolism (VTE): VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Evaluate patients with signs or symptoms consistent with DVT or PE. ( 5.3 ) Blood Pressure Increases: Testosterone Gel 1.62% can increase blood pressure, which can increase cardiovascular risk over time. Measure blood pressure periodically. Not recommended for use in men with uncontrolled hypertension ( 5.5 ) Potential for Adverse Effects on Spermatogenesis: Exogenous administration of androgens may lead to azoospermia ( 5.8 ) Edema: Edema with or without congestive heart failure (CHF) may be a complication in patients with preexisting cardiac, renal, or hepatic disease ( 5.10 , 6.2 ) Sleep apnea: Sleep apnea may occur in those with risk factors ( 5.12 ) Monitor serum testosterone, prostate specific antigen (PSA), hemoglobin, hematocrit, liver function tests and lipid concentrations periodically ( 5.4 , 5.2 , 5.9 , 5.13 ) Flammability: Testosterone gel 1.62% is flammable until dry ( 5.16 ) 5.1 Potential for Secondary Exposure to Testosterone Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using testosterone gel 1.62% [see DOSAGE AND ADMINISTRATION ( 2.2 ), USE IN SPECIFIC POPULATIONS ( 8.1 ) and CLINICAL PHARMACOLOGY ( 12.3 )] . Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified. 5.2 Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration.

quire lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events. 5.3 Venous Thromboembolism There have been postmarketing reports of venous thromboembolic events (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products such as testosterone gel 1.62%. In the Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) Study, a randomized, double-blind, placebo-controlled, cardiovascular (CV) outcomes study, compared to placebo, testosterone gel 1.62% was associated with a numerically higher incidence of VTE (1.7% vs 1.2%) which included DVT (0.6% vs 0.5%) and PE events (0.9% vs 0.5%) [see Adverse Reactions ( 6.1 )]. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with testosterone gel 1.62% and initiate appropriate workup and management [see ADVERSE REACTIONS ( 6.2 )] . 5.4 Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at increased risk for prostate cancer. Evaluation of patients for prostate cancer prior to initiating and during treatment with androgens [see CONTRAINDICATIONS ( 4 ), ADVERSE REACTIONS ( 6.1 ) and NONCLINICAL TOXICOLOGY ( 13.1 )]. 5.5 Blood Pressure Increases Testosterone gel 1% can increase blood pressure. In an ambulatory blood pressure monitoring (ABPM) study, testosterone gel 1.62% increased the mean systolic/diastolic blood pressure by 1.9/1.3 mm Hg from baseline after 16 weeks of treatment. In patients with hypertension on antihypertensive therapy, testosterone gel 1.62% increased the mean systolic/diastolic BP by 3.0/2.2 mm Hg from baseline. Blood pressure increases can increase cardiovascular (CV) risk over time. The CV risk associated with testosterone gel 1.62% was evaluated in TRAVERSE, a randomized, double-blind, placebo-controlled, CV outcomes study in men with a history of CV disease or multiple CV risk factors. In TRAVERSE, mean systolic blood pressure in the group treated with testosterone gel 1.62% increased by 1.0 mm Hg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 mm Hg was observed in the placebo group at this timepoint, for a mean between-group difference of 1.5 mm Hg. However, the incidences of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction [MI] and non-fatal stroke, were similar between treatment groups (7% for testosterone gel 1.62% vs 7.3% for placebo) [See Adverse Reactions ( 6.1 )]. Monitor blood pressure periodically in men using testosterone gel 1.62%, especially men with hypertension. testosterone gel 1.62% is not recommended for use in patients with uncontrolled hypertension. 5.6 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids.

is not recommended for use in patients with uncontrolled hypertension. 5.6 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see DRUG ABUSE AND DEPENDENCE ( 9 )]. If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. 5.7 Not for use in Women Due to the lack of controlled evaluations in women and potential virilizing effects, testosterone gel 1.62% is not indicated for use in women [see CONTRAINDICATIONS ( 4 ) and USE IN SPECIFIC POPULATIONS ( 8.1 , 8.2 )]. 5.8 Potential for Adverse Effects on Spermatogenesis With large doses of exogenous androgens, including testosterone gel 1.62%, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH possibly leading to adverse effects on semen parameters including sperm count. 5.9 Hepatic Adverse Effects Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. Testosterone gel 1.62% is not known to cause these adverse effects. 5.10 Edema Androgens, including testosterone gel 1.62%, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease [see ADVERSE REACTIONS ( 6.2 )] . 5.11 Gynecomastia Gynecomastia may develop and persist in patients being treated with androgens, including testosterone gel 1.62%, for hypogonadism. 5.12 Sleep Apnea The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. 5.13 Lipid Changes Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy, such as testosterone gel 1.62%. Monitor the lipid profile periodically, particularly after starting testosterone therapy. 5.14 Hypercalcemia Androgens, including testosterone gel 1.62%, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. 5.15 Decreased Thyroxine-binding Globulin Androgens, including testosterone gel 1.62%, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. 5.16 Flammability Alcohol based products, including testosterone gel 1.62%, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the testosterone gel 1.62% has dried.

6 ADVERSE REACTIONS The most common adverse reaction (incidence ≥ 5%) is an increase in prostate specific antigen (PSA). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Testosterone gel 1.62% was evaluated in a two-phase, 364-day, controlled clinical study. The first phase was a multi-center, randomized, double-blind, parallel-group, placebo-controlled period of 182 days, in which 234 hypogonadal men were treated with testosterone gel 1.62% and 40 received placebo. Patients could continue in an open-label, non-comparative, maintenance period for an additional 182 days [see CLINICAL STUDIES ( 14.1 )] . The most common adverse reaction reported in the double-blind period was increased prostate specific antigen (PSA) reported in 26 testosterone gel 1.62%-treated patients (11.1%). In 17 patients, increased PSA was considered an adverse event by meeting one of the two pre-specified criteria for abnormal PSA values, defined as (1) average serum PSA >4 ng/mL based on two separate determinations, or (2) an average change from baseline in serum PSA of greater than 0.75 ng/mL on two determinations. During the 182-day, double-blind period of the clinical trial, the mean change in serum PSA value was 0.14 ng/mL for patients receiving testosterone gel 1.62% and -0.12 ng/mL for the patients in the placebo group. During the double-blind period, seven patients had a PSA value >4.0 ng/mL, four of these seven patients had PSA less than or equal to 4.0 ng/mL upon repeat testing. The other three patients did not undergo repeat PSA testing. During the 182-day, open-label period of the study, the mean change in serum PSA values was 0.10 ng/mL for both patients continuing on active therapy and patients transitioning onto active from placebo. During the open-label period, three patients had a serum PSA value > 4.0 ng/mL, two of whom had a serum PSA less than or equal to 4.0 ng/mL upon repeated testing. The other patient did not undergo repeat PSA testing. Among previous placebo patients, 3 of 28 (10.7%), had increased PSA as an adverse event in the open-label period. Table 3 shows adverse reactions reported by >2% of patients in the 182-day, double-blind period of the testosterone gel 1.62% clinical trial and more frequent in the testosterone gel 1.62% treated group versus placebo. Table 3: Adverse Reactions Reported in >2% of Patients in the 182-Day, Double-Blind Period of Testosterone Gel 1.62% Clinical Trial Number (%) of Patients Adverse Reaction Testosterone Gel 1.62% N=234 Placebo N=40 PSA increased * 26 (11.1%) 0% Emotional lability ** 6 (2.6%) 0% Hypertension 5 (2.1%) 0% Hematocrit or hemoglobin increased 5 (2.1%) 0% Contact dermatitis *** 5 (2.1%) 0% * PSA increased includes: PSA values that met pre-specified criteria for abnormal PSA values (an average change from baseline > 0.75 ng/mL and/or an average PSA value >4.0 ng/mL based on two measurements) as well as those reported as adverse events. ** Emotional lability includes: mood swings, affective disorder, impatience, anger, and aggression.

values that met pre-specified criteria for abnormal PSA values (an average change from baseline > 0.75 ng/mL and/or an average PSA value >4.0 ng/mL based on two measurements) as well as those reported as adverse events. ** Emotional lability includes: mood swings, affective disorder, impatience, anger, and aggression. *** Contact dermatitis includes: 4 patients with dermatitis at non-application sites. Other adverse reactions occurring in less than or equal to 2% of testosterone gel 1.62%-treated patients and more frequently than placebo included: frequent urination, and hyperlipidemia. In the open-label period of the study (N=191), the most commonly reported adverse reaction (experienced by greater than 2% of patients) was increased PSA (n=13; 6.2%) and sinusitis. Other adverse reactions reported by less than or equal to 2% of patients included increased hemoglobin or hematocrit, hypertension, acne, libido decreased, insomnia, and benign prostatic hypertrophy. During the 182-day, double-blind period of the clinical trial, 25 testosterone gel 1.62%-treated patients (10.7%) discontinued treatment because of adverse reactions. These adverse reactions included 17 patients with PSA increased and 1 report each of: hematocrit increased, blood pressure increased, frequent urination, diarrhea, fatigue, pituitary tumor, dizziness, skin erythema and skin nodule (same patient – neither at application site), vasovagal syncope, and diabetes mellitus. During the 182-day, open-label period, 9 patients discontinued treatment because of adverse reactions. These adverse reactions included 6 reports of PSA increased, 2 of hematocrit increased, and 1 each of triglycerides increased and prostate cancer. Application Site Reactions In the 182-day double-blind period of the study, application site reactions were reported in two (2/234; 0.9%) patients receiving testosterone gel 1.62%, both of which resolved. Neither of these patients discontinued the study due to application site adverse reactions. In the open-label period of the study, application site reactions were reported in three (3/219; 1.4%) additional patients that were treated with testosterone gel 1.62%. None of these subjects were discontinued from the study due to application site reactions. Blood Pressure Increases In a 4-month clinical study, 24-hour ambulatory blood pressure monitoring (ABPM) was conducted on 246 patients. ABPM was conducted at baseline and at Week 16 of testosterone gel 1.62% therapy. A total of 169 patients had acceptable ABPM recordings at both baseline and Week 16 and were at least 85% compliant with study drug. In that group, the mean change in 24hour systolic blood pressure (BP) and diastolic BP from baseline to end-of-treatment at Week 16 (n=169) was 1.9 mm Hg (95% CI 0.6, 3.1) and 1.3 mm Hg (95% CI 0.5, 2.1), respectively. In patients with a history of hypertension who were receiving antihypertensive therapy, the mean ABPM systolic and diastolic BP increased by 3.0 mm Hg [95% CI 0.8, 5.2] and 2.2 mm Hg [95% CI 0.8, 3.5], respectively [n=72]). In patients with no history of hypertension, the mean systolic and diastolic blood pressure increased by 1.2 mm Hg [95% CI -0.2, 2.7] and 0.9 mm Hg [95% CI -0.1, 1.8], respectively [n=91]. Four patients (2.8 %) on testosterone gel 1.62%, all of whom were receiving antihypertensive medications at baseline, either started new antihypertensive medications (n=2) or had their antihypertensive medication regimen adjusted (n=2) during the ABPM study. Of the 246 patients in the ABPM study who used testosterone gel 1.62%, 10 patients (4.1%) were reported to have either an adverse reaction of hypertension (5 patients, 2.0%) or increased blood pressure (5 patients, 2.0%).

tions (n=2) or had their antihypertensive medication regimen adjusted (n=2) during the ABPM study. Of the 246 patients in the ABPM study who used testosterone gel 1.62%, 10 patients (4.1%) were reported to have either an adverse reaction of hypertension (5 patients, 2.0%) or increased blood pressure (5 patients, 2.0%). Cardiovascular Outcomes TRAVERSE was a randomized, double-blind, cardiovascular outcomes study to assess the cardiovascular (CV) safety of testosterone gel 1.62% compared to placebo in 5198 hypogonadal men aged 45 to 80 years with a history of CV disease or with multiple CV risk factors. The primary outcome was the incidence of the composite endpoint of major adverse cardiovascular events (MACE), consisting of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. The mean duration of therapy was approximately 22 months. The mean duration of follow-up was 33 months. Approximately 61% of all patients discontinued testosterone gel 1.62% or placebo therapy. The mean (±SD) daily dose of testosterone was 65±22 mg. The mean patient age (±SD) was 63.3 (7.9) years, with 2452 patients aged 65 years or more (47%); 2847 (about 55%) patients had pre-existing cardiovascular disease, whereas 2357 (about 45%) patients had an elevated cardiovascular risk at baseline, and mean BMI was 35kg/m2. Approximately 80% of patients were White, 17% were Black, and 3% were of other races or ethnic groups. Approximately 69%, 84%, and 93% had diabetes mellitus, hyperlipidemia, and hypertension, respectively. The mean serum testosterone concentration at baseline in patients receiving testosterone gel 1.62% was 220.4 ng/dL (n=2596).The mean serum testosterone concentrations at 12 months, 24 months, 36 months, and 48 months in patients receiving testosterone gel 1.62% were 440.5 ng/dL (n=1683), 420.9 ng/dl (n=1125), 428.7 ng/dL (n=731), and 365.2 ng/dL (n=220), respectively. For patients treated with testosterone gel 1.62%, the incidence of MACE was 7.0% (n=182 events) and for those receiving placebo, the incidence of MACE was 7.3% (n=190 events). The study demonstrated non-inferiority of testosterone gel 1.62% versus placebo because the upper bound of 95% CI was less than the pre-specified risk margin, of 1.5 for MACE (Hazard Ratio 0.96 [95% CI: 0.78, 1.17]). Additional Adverse Reactions Reported in TRAVERSE Additional adverse reactions reported in TRAVERSE at an incidence rate >2% in either treatment group and greater in testosterone gel 1.62% versus placebo included: nonfatal arrythmias warranting intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and bone fracture (3.5% vs 2.5%). For the adverse reaction of bone fracture, each event was adjudicated by clinical review. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of testosterone gel 1.62%. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 4).

ience The following adverse reactions have been identified during post approval use of testosterone gel 1.62%. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 4). Table 4: Adverse Reactions from Post Approval Experience of testosterone gel 1.62% by System Organ Class System Organ Class Adverse Reaction Blood and lymphatic system disorders: Elevated hemoglobin or hematocrit, polycythemia, anemia Cardiovascular disorders: Myocardial infarction, stroke Endocrine disorders: Hirsutism Gastrointestinal disorders: Nausea General disorders: Asthenia, edema, malaise Genitourinary disorders: Impaired urination* Hepatobiliary disorders: Abnormal liver function tests Investigations: Lab test abnormal**, elevated PSA, electrolyte changes (nitrogen, calcium, potassium [includes hypokalemia] , phosphorus, sodium), impaired glucose tolerance, hyperlipidemia, HDL, fluctuating testosterone levels, weight increase Neoplasms: Prostate cancer Nervous system disorders: Dizziness, headache, insomnia, sleep apnea Psychiatric disorders: Amnesia, anxiety, depression, hostility, emotional lability, decreased libido, nervousness Reproductive system and breast disorders: Gynecomastia, mastodynia, oligospermia, priapism (frequent or prolonged erections), prostate enlargement, BPH, testis disorder*** Respiratory disorders: Dyspnea Skin and subcutaneous tissue disorders: Acne, alopecia, application site reaction (discolored hair, dry skin, erythema, paresthesia, pruritus, rash), skin dry, pruritus, sweating Vascular disorders: Hypertension, vasodilation (hot flushes), venous thromboembolism * Impaired urination includes nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream ** Lab test abnormal includes elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, or elevated serum creatinine *** Testis disorder includes atrophy or non-palpable testis, varicocele, testis sensitivity or tenderness Secondary Exposure to Testosterone in Children Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user's shirts and/or other fabric, such as towels and sheets [see WARNINGS AND PRECAUTIONS ( 5.1 )] .

<table ID="ID85" width="0" styleCode="Noautorules"><caption> Table 3: Adverse Reactions Reported in &gt;2% of Patients in the 182-Day, Double-Blind Period of Testosterone Gel 1.62% Clinical Trial </caption><col width="235"/><col width="163"/><col width="124"/><tbody><tr><td valign="top" styleCode="Lrule Toprule Botrule Rrule" align="left"> </td><td valign="top" styleCode=" Toprule Botrule" align="right"><content styleCode="bold"> Number (%)</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="left"><content styleCode="bold"> of Patients</content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Adverse Reaction </content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> Testosterone Gel 1.62% N=234 </content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> Placebo </content> <content styleCode="bold"> N=40 </content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> PSA increased^* </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 26 (11.1%) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0% </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Emotional lability^** </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 6 (2.6%) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0% </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Hypertension </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5 (2.1%) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0% </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Hematocrit or hemoglobin increased </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5 (2.1%) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0% </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> Contact dermatitis^*** </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 5 (2.1%) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 0% </td></tr><tr><td colspan="3" valign="top" styleCode="Lrule Botrule Rrule" align="left">^*<content styleCode="bold"><content styleCode="italics">PSA increased </content></content> includes: PSA values that met pre-specified criteria for abnormal PSA values (an average change from baseline &gt; 0.75 ng/mL and/or an average PSA value &gt;4.0 ng/mL based on two measurements) as well as those reported as adverse events. </td></tr><tr><td colspan="3" valign="top" styleCode="Lrule Botrule Rrule" align="left">^**<content styleCode="bold"><content styleCode="italics">Emotional lability </content></content> includes: mood swings, affective disorder, impatience, anger, and aggression. </td></tr><tr><td colspan="3" valign="top" styleCode="Lrule Botrule Rrule" align="left">^***<content styleCode="bold"><content styleCode="italics">Contact dermatitis </content></content> includes: 4 patients with dermatitis at non-application sites. </td></tr></tbody></table>

mpatience, anger, and aggression. </td></tr><tr><td colspan="3" valign="top" styleCode="Lrule Botrule Rrule" align="left">^***<content styleCode="bold"><content styleCode="italics">Contact dermatitis </content></content> includes: 4 patients with dermatitis at non-application sites. </td></tr></tbody></table> <table ID="ID234" width="590" styleCode="Noautorules"><caption> Table 4: Adverse Reactions from Post Approval Experience of testosterone gel 1.62% by System Organ Class </caption><col width="133"/><col width="457"/><tbody><tr><td styleCode="Lrule Toprule Botrule Rrule" align="left"><content styleCode="bold"> System Organ Class </content> </td><td styleCode=" Toprule Botrule Rrule" align="left"><content styleCode="bold"> Adverse Reaction </content> </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Blood and lymphatic system disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Elevated hemoglobin or hematocrit, polycythemia, anemia </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Cardiovascular disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Myocardial infarction, stroke </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Endocrine disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Hirsutism </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Gastrointestinal disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Nausea </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> General disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Asthenia, edema, malaise </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Genitourinary disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Impaired urination* </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Hepatobiliary disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Abnormal liver function tests </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Investigations: </content> </td><td styleCode=" Botrule Rrule" align="left"> Lab test abnormal**, elevated PSA, electrolyte changes (nitrogen, calcium, potassium [includes hypokalemia]<content styleCode="bold"> , </content> phosphorus, sodium), impaired glucose tolerance, hyperlipidemia, HDL, fluctuating testosterone levels, weight increase </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Neoplasms: </content> </td><td styleCode=" Botrule Rrule" align="left"> Prostate cancer </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Nervous system disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Dizziness, headache, insomnia, sleep apnea </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Psychiatric disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Amnesia, anxiety, depression, hostility, emotional lability, decreased libido, nervousness </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Reproductive system and breast disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Gynecomastia, mastodynia, oligospermia, priapism (frequent or prolonged erections), prostate enlargement, BPH, testis disorder*** </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Respiratory disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Dyspnea </td></tr><tr><td styleCode="L

ia, oligospermia, priapism (frequent or prolonged erections), prostate enlargement, BPH, testis disorder*** </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Respiratory disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Dyspnea </td></tr><tr><td styleCode="L rule Botrule Rrule" align="left"><content styleCode="bold"> Skin and subcutaneous tissue disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Acne, alopecia, application site reaction (discolored hair, dry skin, erythema, paresthesia, pruritus, rash), skin dry, pruritus, sweating </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Vascular disorders: </content> </td><td styleCode=" Botrule Rrule" align="left"> Hypertension, vasodilation (hot flushes), venous thromboembolism </td></tr><tr><td colspan="2" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> * <content styleCode="italics">Impaired urination </content> includes </content> nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream </td></tr><tr><td colspan="2" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> **<content styleCode="italics">Lab test abnormal </content> includes </content> elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, or elevated serum creatinine </td></tr><tr><td colspan="2" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> ***<content styleCode="italics">Testis disorder </content> includes </content> atrophy or non-palpable testis, varicocele, testis sensitivity or tenderness </td></tr></tbody></table>

7 DRUG INTERACTIONS Androgens may decrease blood glucose and therefore may decrease insulin requirements in diabetic patients ( 7.1 ) Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended ( 7.2 ) Use of testosterone with adrenocorticotrophic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease ( 7.3 ) 7.1 Insulin Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease insulin requirements. 7.2 Oral Anticoagulants Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy. 7.3 Corticosteroids The concurrent use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.

8 USE IN SPECIFIC POPULATIONS There are insufficient long-term safety data in geriatric patients using testosterone gel 1.62% to assess the potential risks of cardiovascular disease and prostate cancer. ( 8.5 ) 8.1 Pregnancy Risk Summary Testosterone gel 1.62% is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see CONTRAINDICATIONS ( 4 ) and CLINICAL PHARMACOLOGY ( 12.1 )] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes. Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy. 8.2 Lactation Risk Summary Testosterone gel 1.62% is not indicated for use in women. 8.3 Females and Males of Reproductive Potential Infertility Testis disorder, testicular atrophy, and oligospermia have been identified during use of testosterone gel 1.62% [see ADVERSE REACTIONS ( 6.1 , 6.2 )] . During treatment with large doses of exogenous androgens, including testosterone gel 1.62%, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see WARNINGS AND PRECAUTIONS ( 5.8 )] . Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see DRUG ABUSE AND DEPENDENCE ( 9.2 )] . With either type of use, the impact on fertility may be irreversible. 8.4 Pediatric Use The safety and effectiveness of testosterone gel 1.62% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses. 8.5 Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing testosterone gel 1.62%, 21 were over 65 years of age.

sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing testosterone gel 1.62%, 21 were over 65 years of age. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer. Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH. 8.6 Renal Impairment No studies were conducted involving patients with renal impairment. 8.7 Hepatic Impairment No studies were conducted in patients with hepatic impairment.

8.1 Pregnancy Risk Summary Testosterone gel 1.62% is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see CONTRAINDICATIONS ( 4 ) and CLINICAL PHARMACOLOGY ( 12.1 )] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes. Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy.

8.3 Females and Males of Reproductive Potential Infertility Testis disorder, testicular atrophy, and oligospermia have been identified during use of testosterone gel 1.62% [see ADVERSE REACTIONS ( 6.1 , 6.2 )] . During treatment with large doses of exogenous androgens, including testosterone gel 1.62%, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see WARNINGS AND PRECAUTIONS ( 5.8 )] . Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see DRUG ABUSE AND DEPENDENCE ( 9.2 )] . With either type of use, the impact on fertility may be irreversible.

8.4 Pediatric Use The safety and effectiveness of testosterone gel 1.62% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

8.5 Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing testosterone gel 1.62%, 21 were over 65 years of age. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer. Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH.

9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance Testosterone gel 1.62% contains testosterone, a Schedule III controlled substance in the Controlled Substances Act. 9.2 Abuse Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice. Abuse-Related Adverse Reactions Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression. The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility. The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty. Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 9.3 Dependence Behaviors Associated with Addiction Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors: Taking greater dosages than prescribed Continued drug use despite medical and social problems due to drug use Spending significant time to obtain the drug when supplies of the drug are interrupted Giving a higher priority to drug use than other obligations Having difficulty in discontinuing the drug despite desires and attempts to do so Experiencing withdrawal symptoms upon abrupt discontinuation of use Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

10 OVERDOSAGE There is a single report of acute overdosage after parenteral administration of an approved testosterone product in the literature. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident. There were no reports of overdosage in the testosterone gel 1.62% clinical trial. Treatment of overdosage would consist of discontinuation of testosterone gel 1.62%, washing the application site with soap and water, and appropriate symptomatic and supportive care.

11 DESCRIPTION Testosterone gel 1.62% for topical use is a clear, colorless gel containing testosterone. Testosterone is an androgen. Testosterone gel 1.62% is available in a metered-dose pump. The active pharmacologic ingredient in testosterone gel 1.62% is testosterone. Testosterone USP is a white to almost white powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is: The inactive ingredients in testosterone gel 1.62% are: carbomer homopolymer type C, dehydrated alcohol (68.1%w/w), isopropyl myristate, sodium hydroxide and purified water. Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement; vocal cord thickening; and alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). 12.2 Pharmacodynamics No specific pharmacodynamic studies were conducted using testosterone gel 1.62%. 12.3 Pharmacokinetics Absorption Testosterone gel 1.62% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (300 to 1000 ng/dL) seen in healthy men. Testosterone gel 1.62% provides continuous topical delivery of testosterone for 24 hours following once daily application to clean, dry, intact skin of the shoulders and upper arms. Average serum testosterone concentrations over 24 hours (C avg ) observed when testosterone gel 1.62% was applied to the upper arms/shoulders were comparable to average serum testosterone concentrations (C avg ) when testosterone gel 1.62% was applied using a rotation method utilizing the abdomen and upper arms/shoulders. The rotation of abdomen and upper arms/shoulders was a method used in the pivotal clinical trial [see CLINICAL STUDIES ( 14.1 )]. Figure 2: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients Following Testosterone Gel 1.62% Once-Daily Application of 81 mg of Testosterone (N=33) for 7 Days Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT. Excretion There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. When testosterone gel 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48 to 72 hours after administration of the last dose.

ose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. When testosterone gel 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48 to 72 hours after administration of the last dose. Potential for testosterone transfer: The potential for testosterone transfer following administration of testosterone gel 1.62% when it was applied only to upper arms/shoulders was evaluated in two clinical studies of males dosed with testosterone gel 1.62% and their untreated female partners. In one study, 8 male subjects applied a single dose of testosterone gel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes. Serum concentrations of testosterone were monitored in female subjects for 24 hours after contact occurred. After direct skin-to-skin contact with the site of application, mean testosterone C avg and C max in female subjects increased by 280% and 267%, respectively, compared to mean baseline testosterone concentrations. In a second study evaluating transfer of testosterone, 12 male subjects applied a single dose of testosterone gel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt. When a t-shirt was used to cover the site of application, mean testosterone C avg and C max in female subjects increased by 6% and 11%, respectively, compared to mean baseline testosterone concentrations. A separate study was conducted to evaluate the potential for testosterone transfer from 16 males dosed with testosterone gel 1.62% 81 mg when it was applied to abdomen only for 7 days, a site of application not approved for testosterone gel 1.62%. Two (2) hours after application to the males on each day, the female subjects rubbed their abdomens for 15 minutes to the abdomen of the males. The males had covered the application area with a T-shirt. The mean testosterone C avg and C max in female subjects on day 1 increased by 43% and 47%, respectively, compared to mean baseline testosterone concentrations. The mean testosterone C avg and C max in female subjects on day 7 increased by 60% and 58%, respectively, compared to mean baseline testosterone concentrations. Effect of showering : In a randomized, 3-way (3 treatment periods without washout period) crossover study in 24 hypogonadal men, the effect of showering on testosterone exposure was assessed after once daily application of testosterone gel 1.62% 81 mg to upper arms/shoulders for 7 days in each treatment period. On the 7 th day of each treatment period, hypogonadal men took a shower with soap and water at either 2, 6, or 10 hours after drug application. The effect of showering at 2 or 6 hours post-dose on Day 7 resulted in 13% and 12% decreases in mean C avg , respectively, compared to Day 6 when no shower was taken after drug application. Showering at 10 hours after drug application had no effect on bioavailability. The amount of testosterone remaining in the outer layers of the skin at the application site on the 7th day was assessed using a tape stripping procedure and was reduced by at least 80% after showering 2 to 10 hours post-dose compared to on the 6th day when no shower was taken after drug application. Effect of hand washing In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated.

showering 2 to 10 hours post-dose compared to on the 6th day when no shower was taken after drug application. Effect of hand washing In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated. Subjects used their hands to apply the maximum dose (81 mg testosterone) of testosterone gel 1.62% to their upper arms and shoulders. Within 1 minute of applying the gel, subjects either washed or did not wash their hands prior to study personnel wiping the subjects' hands with ethanol dampened gauze pads. The gauze pads were then analyzed for residual testosterone content. A mean (SD) of 0.1 (0.04) mg of residual testosterone (0.12% of the actual applied dose of testosterone, and a 96% reduction compared to when hands were not washed) was recovered after washing hands with water and soap. Effect of sunscreen or moisturizing lotion on absorption of testosterone : In a randomized, 3-way (3 treatment periods without washout period) crossover study in 18 hypogonadal males, the effect of applying a moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the testosterone gel 1.62% application site 1 hour after the application of testosterone gel 1.62% 40.5 mg. Application of moisturizing lotion increased mean testosterone C avg and C max by 14% and 17%, respectively, compared to testosterone gel 1.62% administered alone. Application of sunscreen increased mean testosterone C avg and C max by 8% and 13%, respectively, compared to testosterone gel 1.62% applied alone. Image 1

12.1 Mechanism of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement; vocal cord thickening; and alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

12.3 Pharmacokinetics Absorption Testosterone gel 1.62% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (300 to 1000 ng/dL) seen in healthy men. Testosterone gel 1.62% provides continuous topical delivery of testosterone for 24 hours following once daily application to clean, dry, intact skin of the shoulders and upper arms. Average serum testosterone concentrations over 24 hours (C avg ) observed when testosterone gel 1.62% was applied to the upper arms/shoulders were comparable to average serum testosterone concentrations (C avg ) when testosterone gel 1.62% was applied using a rotation method utilizing the abdomen and upper arms/shoulders. The rotation of abdomen and upper arms/shoulders was a method used in the pivotal clinical trial [see CLINICAL STUDIES ( 14.1 )]. Figure 2: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients Following Testosterone Gel 1.62% Once-Daily Application of 81 mg of Testosterone (N=33) for 7 Days Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT. Excretion There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. When testosterone gel 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48 to 72 hours after administration of the last dose. Potential for testosterone transfer: The potential for testosterone transfer following administration of testosterone gel 1.62% when it was applied only to upper arms/shoulders was evaluated in two clinical studies of males dosed with testosterone gel 1.62% and their untreated female partners. In one study, 8 male subjects applied a single dose of testosterone gel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes. Serum concentrations of testosterone were monitored in female subjects for 24 hours after contact occurred. After direct skin-to-skin contact with the site of application, mean testosterone C avg and C max in female subjects increased by 280% and 267%, respectively, compared to mean baseline testosterone concentrations. In a second study evaluating transfer of testosterone, 12 male subjects applied a single dose of testosterone gel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt.

, 12 male subjects applied a single dose of testosterone gel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt. When a t-shirt was used to cover the site of application, mean testosterone C avg and C max in female subjects increased by 6% and 11%, respectively, compared to mean baseline testosterone concentrations. A separate study was conducted to evaluate the potential for testosterone transfer from 16 males dosed with testosterone gel 1.62% 81 mg when it was applied to abdomen only for 7 days, a site of application not approved for testosterone gel 1.62%. Two (2) hours after application to the males on each day, the female subjects rubbed their abdomens for 15 minutes to the abdomen of the males. The males had covered the application area with a T-shirt. The mean testosterone C avg and C max in female subjects on day 1 increased by 43% and 47%, respectively, compared to mean baseline testosterone concentrations. The mean testosterone C avg and C max in female subjects on day 7 increased by 60% and 58%, respectively, compared to mean baseline testosterone concentrations. Effect of showering : In a randomized, 3-way (3 treatment periods without washout period) crossover study in 24 hypogonadal men, the effect of showering on testosterone exposure was assessed after once daily application of testosterone gel 1.62% 81 mg to upper arms/shoulders for 7 days in each treatment period. On the 7 th day of each treatment period, hypogonadal men took a shower with soap and water at either 2, 6, or 10 hours after drug application. The effect of showering at 2 or 6 hours post-dose on Day 7 resulted in 13% and 12% decreases in mean C avg , respectively, compared to Day 6 when no shower was taken after drug application. Showering at 10 hours after drug application had no effect on bioavailability. The amount of testosterone remaining in the outer layers of the skin at the application site on the 7th day was assessed using a tape stripping procedure and was reduced by at least 80% after showering 2 to 10 hours post-dose compared to on the 6th day when no shower was taken after drug application. Effect of hand washing In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated. Subjects used their hands to apply the maximum dose (81 mg testosterone) of testosterone gel 1.62% to their upper arms and shoulders. Within 1 minute of applying the gel, subjects either washed or did not wash their hands prior to study personnel wiping the subjects' hands with ethanol dampened gauze pads. The gauze pads were then analyzed for residual testosterone content. A mean (SD) of 0.1 (0.04) mg of residual testosterone (0.12% of the actual applied dose of testosterone, and a 96% reduction compared to when hands were not washed) was recovered after washing hands with water and soap. Effect of sunscreen or moisturizing lotion on absorption of testosterone : In a randomized, 3-way (3 treatment periods without washout period) crossover study in 18 hypogonadal males, the effect of applying a moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the testosterone gel 1.62% application site 1 hour after the application of testosterone gel 1.62% 40.5 mg.

a moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the testosterone gel 1.62% application site 1 hour after the application of testosterone gel 1.62% 40.5 mg. Application of moisturizing lotion increased mean testosterone C avg and C max by 14% and 17%, respectively, compared to testosterone gel 1.62% administered alone. Application of sunscreen increased mean testosterone C avg and C max by 8% and 13%, respectively, compared to testosterone gel 1.62% applied alone.

14 CLINICAL STUDIES 14.1 Clinical Trials in Hypogonadal Males Testosterone gel 1.62% was evaluated in a multi-center, randomized, double-blind, parallel-group, placebo-controlled study (182-day double-blind period) in 274 hypogonadal men with body mass index (BMI) 18 to 40 kg/m 2 and 18 to 80 years of age (mean age 53.8 years). The patients had an average serum testosterone concentration of <300 ng/dL, as determined by two morning samples collected on the same visit. Patients were Caucasian 83%, Black 13%, Asian or Native American 4%. 7.5% of patients were Hispanic. Patients were randomized to receive active treatment or placebo using a rotation method utilizing the abdomen and upper arms/shoulders for 182 days. All patients were started at a daily dose of 40.5 mg (two pump actuations) testosterone gel 1.62% or matching placebo on Day 1 of the study. Patients returned to the clinic on Day 14, Day 28, and Day 42 for predose serum total testosterone assessments. The patient's daily dose was titrated up or down in 20.25 mg increments if the predose serum testosterone value was outside the range of 350 to 750 ng/dL. The study included four active testosterone gel 1.62% doses: 20.25 mg, 40.5 mg, 60.75 mg, and 81 mg daily. The primary endpoint was the percentage of patients with C avg within the normal range of 300 to 1000 ng/dL on Day 112. In patients treated with testosterone gel 1.62%, 81.6% (146/179) had C avg within the normal range at Day 112. The secondary endpoint was the percentage of patients, with C max above three pre-determined limits. The percentages of patients with C max greater than 1500 ng/dL, and between 1800 and 2499 ng/dL on Day 112 were 11.2% and 5.5%, respectively. Two patients had a C max >2500 ng/dL on Day 112 (2510 ng/dL and 2550 ng/dL, respectively); neither of these 2 patients demonstrated an abnormal C max on prior or subsequent assessments at the same dose. Patients could agree to continue in an open-label, active treatment maintenance period of the study for an additional 182 days. Dose titrations on Days 14, 28, and 42 resulted in final doses of 20.25 mg to 81 mg on Day 112 as shown in Table 5. Table 5: Mean (SD) Testosterone Concentrations (Cavg and Cmax) by final dose on Days 112 and 364 Final Dose on Day 112 Parameter Placebo (n=27) 20.25 mg (n=12) 40.5 mg (n=34) 60.75 mg (n=54) 81 mg (n=79) All Active (n=179) C avg (ng/dL) 303 (135) 457 (275) 524 (228) 643 (285) 537 (240) 561 (259) C max (ng/dL) 450 (349) 663 (473) 798 (439) 958 (497) 813 (479) 845 (480) Final Dose on Day 364 20.25 mg (n=7) 40.5 mg (n=26) 60.75 mg (n=29) 81 mg (n=74) Continuing Active (n=136) C avg (ng/dL) 386 (130) 474 (176) 513 (222) 432 (186) 455 (192) C max (ng/dL) 562 (187) 715 (306) 839 (568) 649 (329) 697 (389) Figure 3 summarizes the pharmacokinetic profile of total testosterone in patients completing 112 days of testosterone gel 1.62% treatment administered as a starting dose of 40.5 mg of testosterone (2 pump actuations) for the initial 14 days followed by possible titration according to the follow-up testosterone measurements. Figure 3: Mean (±SD) Steady-State Serum Total Testosterone Concentrations on Day 112 Efficacy was maintained in the group of men that received testosterone gel 1.62% for one full year. In that group, 78% (106/136) had average serum testosterone concentrations in the normal range at Day 364. Figure 4 summarizes the mean total testosterone profile for these patients on Day 364.

Concentrations on Day 112 Efficacy was maintained in the group of men that received testosterone gel 1.62% for one full year. In that group, 78% (106/136) had average serum testosterone concentrations in the normal range at Day 364. Figure 4 summarizes the mean total testosterone profile for these patients on Day 364. Figure 4: Mean (±SD) Steady-State Serum Total Testosterone Concentrations on Day 364 The mean estradiol and DHT concentration profiles paralleled the changes observed in testosterone. The levels of LH and FSH decreased with testosterone treatment. The decreases in levels of LH and FSH are consistent with reports published in the literature of long-term treatment with testosterone. Image 2 Image 3

<table ID="ID146" width="0" styleCode="Noautorules"><col width="102"/><col width="75"/><col width="75"/><col width="75"/><col width="75"/><col width="75"/><col width="148"/><tbody><tr><td valign="top" styleCode="Lrule Toprule Rrule"/><td valign="top" styleCode=" Toprule Botrule" align="left"> </td><td valign="top" styleCode=" Toprule Botrule" align="right"><content styleCode="bold"> Final</content> </td><td valign="top" styleCode=" Toprule Botrule" align="right"><content styleCode="bold"> Dose on</content> </td><td valign="top" styleCode=" Toprule Botrule" align="left"><content styleCode="bold"> Day 112</content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="left"> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="left"> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> Parameter</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> Placebo (n=27)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> 20.25 mg (n=12)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> 40.5 mg (n=34)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> 60.75 mg (n=54)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> 81 mg (n=79)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> All Active </content> <content styleCode="bold"> (n=179)</content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> C</content>_avg<content styleCode="bold"> (ng/dL) </content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 303 (135) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 457 (275) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 524 (228) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 643 (285) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 537 (240) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 561 (259) </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> C</content>_max<content styleCode="bold"> (ng/dL) </content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 450 (349) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 663 (473) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 798 (439) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 958 (497) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 813 (479) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 845 (480) </td></tr><tr><td colspan="7" valign="top" styleCode="Lrule Botrule Rrule" align="center"><content styleCode="bold"> Final Dose on Day 364</content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> </td><td valign="top" styleCode=" Botrule Rrule"/><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> 20.25 mg</content> <content styleCode="bold"> (n=7)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> 40.5 mg</content> <content styleCode="bold"> (n=26)</content> </td><td valign="top" styleCode=" Botrule Rrule" al

rule Rrule" align="center"><content styleCode="bold"> 20.25 mg</content> <content styleCode="bold"> (n=7)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> 40.5 mg</content> <content styleCode="bold"> (n=26)</content> </td><td valign="top" styleCode=" Botrule Rrule" al ign="center"><content styleCode="bold"> 60.75 mg</content> <content styleCode="bold"> (n=29)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> 81 mg</content> <content styleCode="bold"> (n=74)</content> </td><td valign="top" styleCode=" Botrule Rrule" align="center"><content styleCode="bold"> Continuing Active (n=136)</content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> C</content>_avg<content styleCode="bold"> (ng/dL)</content> </td><td valign="top" styleCode=" Botrule Rrule"/><td valign="top" styleCode=" Botrule Rrule" align="center"> 386 (130) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 474 (176) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 513 (222) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 432 (186) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 455 (192) </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"><content styleCode="bold"> C</content>_max<content styleCode="bold"> (ng/dL)</content> </td><td valign="top" styleCode=" Botrule Rrule"/><td valign="top" styleCode=" Botrule Rrule" align="center"> 562 (187) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 715 (306) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 839 (568) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 649 (329) </td><td valign="top" styleCode=" Botrule Rrule" align="center"> 697 (389) </td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Testosterone Gel 1.62% is supplied in non-aerosol, metered-dose pumps that deliver 20.25 mg of testosterone per complete pump actuation. The pumps are composed of plastic and stainless steel and an LDPE/aluminum foil inner liner encased in rigid plastic with a polypropylene cap. Each 88 g metered-dose pump is capable of dispensing 75 g of gel or 60-metered pump actuations; each pump actuation dispenses 1.25 g of gel. NDC Number Package Size 68180-941-11 88 g pump (each pump dispenses 60 metered pump actuations with each pump actuation containing 20.25 mg of testosterone in 1.25 g of gel) Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Used testosterone gel 1.62% pumps should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets.

<table ID="ID155" width="100%"><col width="18%"/><col width="82%"/><tbody><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">NDC </content><content styleCode="bold">Number </content> </td><td align="left" valign="middle" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Package </content><content styleCode="bold">Size </content> </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">68180-941-11 </td><td align="justify" valign="top" styleCode=" Lrule Rrule Botrule Toprule">88 g pump (each pump dispenses 60 metered pump actuations with each pump actuation containing 20.25 mg of testosterone in 1.25 g of gel) </td></tr></tbody></table>

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Patients should be informed of the following: 17.1 Use in Men with Known or Suspected Prostate or Breast Cancer Men with known or suspected prostate or breast cancer should not use testosterone gel 1.62% [see CONTRAINDICATIONS ( 4 ) and WARNINGS AND PRECAUTIONS ( 5.4 )] . 17.2 Potential for Secondary Exposure to Testosterone and Steps to Prevent Secondary Exposure Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men [see WARNINGS AND PRECAUTIONS ( 5.1 )] . Cases of secondary exposure to testosterone have been reported in children. Physicians should advise patients of the reported signs and symptoms of secondary exposure, which may include the following: In children: unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, and aggressive behavior. In women: changes in hair distribution, increase in acne, or other signs of testosterone effects. The possibility of secondary exposure to testosterone gel should be brought to the attention of a healthcare provider. Testosterone gel 1.62% should be promptly discontinued until the cause of virilization is identified. Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from testosterone gel 1.62% in men [see MEDICATION GUIDE] : Children and women should avoid contact with unwashed or unclothed application site(s) of men using testosterone gel 1.62%. Patients using testosterone gel 1.62% should apply the product as directed and strictly adhere to the following: o Wash hands with soap and water immediately after application. o Cover the application site(s) with clothing after the gel has dried. o Wash the application site(s) thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated. In the event that unwashed or unclothed skin to which testosterone gel 1.62% has been applied comes in contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible [see DOSAGE AND ADMINISTRATION ( 2.2 ), WARNINGS AND PRECAUTIONS ( 5.1 ) and CLINICAL PHARMACOLOGY ( 12.3 )] . 17.3 Potential for Venous Thromboembolism Inform patients that testosterone gel 1.62% can cause venous thromboembolism. Advise patients of the signs and symptoms of venous thromboembolism, which may include the following: lower limb pain, edema, or erythema; and dyspnea or chest pain. Advise patients to promptly report the signs and symptoms of venous thromboembolism, discontinue use of testosterone gel 1.62%, and seek urgent medical care. 17.4 Potential for Increase in Blood Pressure Inform patients that testosterone gel 1.62% can increase BP which can increase cardiovascular risk over time. Instruct patients about the importance of monitoring BP periodically while on testosterone gel 1.62%. If BP increases while on testosterone gel 1.62%, antihypertensive medications may need to be started, added, or adjusted to control BP, or testosterone gel 1.62% may need to be discontinued.

diovascular risk over time. Instruct patients about the importance of monitoring BP periodically while on testosterone gel 1.62%. If BP increases while on testosterone gel 1.62%, antihypertensive medications may need to be started, added, or adjusted to control BP, or testosterone gel 1.62% may need to be discontinued. 17.5 Potential Adverse Reactions with Androgens Patients should be informed that treatment with androgens may lead to adverse reactions which include: Changes in urinary habits such as increased urination at night, trouble starting the urine stream, passing urine many times during the day, having an urge to go to the bathroom right away, having a urine accident, being unable to pass urine and weak urine flow. Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness. Too frequent or persistent erections of the penis. Nausea, vomiting, changes in skin color, or ankle swelling. 17.6 Patients Should Be Advised of the Following Instructions for Use Read the Medication Guide before starting testosterone gel 1.62% therapy and to reread it each time the prescription is renewed. Testosterone gel 1.62% should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women. Keep testosterone gel 1.62% out of the reach of children. Testosterone gel 1.62% is an alcohol based product and is flammable; therefore avoid fire, flame or smoking until the gel has dried. It is important to adhere to all recommended monitoring. Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood. Testosterone gel 1.62% is prescribed to meet the patient's specific needs; therefore, the patient should never share testosterone gel 1.62% with anyone. Wait 2 hours before swimming or washing following application of testosterone gel 1.62%. This will ensure that the greatest amount of testosterone gel 1.62% is absorbed into their system. LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc. Manufactured for: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States Manufactured by: Lupin Limited Pithampur (M.P.) – 454 775 India Image

SPL MEDGUIDE MEDICATION GUIDE Testosterone Gel 1.62%, for topical use, CIII (tes TOS ter one) What is the most important information I should know about testosterone gel 1.62%? 1.Testosterone gel 1.62% can transfer from your body to others including, children and women. Children and women should avoid contact with the unwashed or not covered (unclothed) areas where testosterone gel 1.62% has been applied to your skin. Early signs and symptoms of puberty have occurred in young children who have come in direct contact with testosterone by touching areas where men have used testosterone gel 1.62%. Children Signs and symptoms of early puberty in a child when they come in direct contact with testosterone gel 1.62% may include: Abnormal sexual changes: enlarged penis or clitoris. early growth of hair near the vagina or around the penis (pubic hair). erections or acting out sexual urges (sex drive). Behavior problems: acting aggressively, behaving in an angry or violent way. Women Signs and symptoms in women when they come in direct contact with testosterone gel 1.62% may include: changes in body hair. an abnormal increase in pimples (acne). Stop using testosterone gel 1.62% and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have happened through accidental touching of the area where you have applied testosterone gel 1.62%. 2.To lower the risk of transfer of testosterone gel 1.62% from your body to others, follow these important instructions: Apply testosterone gel 1.62% only to your shoulders and upper arms that will be covered by a short sleeve t-shirt. Wash your hands right away with soap and water after applying testosterone gel 1.62%. After the gel has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered. If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water. If a child or woman touches the area where you have applied testosterone gel 1.62%, that area on the child or woman should be washed well with soap and water right away. What is testosterone gel 1.62%? Testosterone gel 1.62% is a prescription medicine that contains testosterone. Testosterone gel 1.62% is used to treat adult males who have low or no testosterone due to certain medical conditions. Your healthcare provider will test your blood before you start and while you are using testosterone gel 1.62%. It is not known if testosterone gel 1.62% is safe or effective to treat men who have low testosterone due to aging. It is not known if testosterone gel 1.62% is safe or effective in children younger than 18 years old. Improper use of testosterone gel 1.62% may affect bone growth in children. Testosterone gel 1.62% is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your testosterone gel 1.62% in a safe place to protect it. Never give your testosterone gel 1.62% to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law. Testosterone gel 1.62% is not meant for use in women. Do not use testosterone gel 1.62% if you: have breast cancer. have or might have prostate cancer. are pregnant. Testosterone gel 1.62% may harm your unborn baby.

the same symptoms you have. Selling or giving away this medicine may harm others and is against the law. Testosterone gel 1.62% is not meant for use in women. Do not use testosterone gel 1.62% if you: have breast cancer. have or might have prostate cancer. are pregnant. Testosterone gel 1.62% may harm your unborn baby. Women who are pregnant should avoid contact with the area of skin where testosterone gel 1.62% has been applied. Before using testosterone gel 1.62%, tell your healthcare provider about all of your medical conditions, including if you: have breast cancer. have or might have prostate cancer . have urinary problems due to an enlarged prostate . have heart problems. have high blood pressure or are being treated for high blood pressure. have kidney or liver problems. have problems breathing while you sleep (sleep apnea). Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using testosterone gel 1.62% with certain other medicines can affect each other. Especially, tell your healthcare provider if you take: insulin medicines that decrease blood clotting (blood thinners) corticosteroids How should I use testosterone gel 1.62%? See the detailed Instructions for Use about how to use testosterone gel 1.62% at the end of this Medication Guide. It is important that you apply testosterone gel 1.62% exactly as your healthcare provider tells you to. Your healthcare provider may change your testosterone gel 1.62% dose. Do not change your testosterone gel 1.62% dose without talking to your healthcare provider. Apply testosterone gel 1.62% at the same time each morning. Testosterone gel 1.62% should be applied after showering or bathing. What are the possible side effects of testosterone gel 1.62%? Testosterone gel 1.62% can cause serious side effects including: See "What is the most important information I should know about testosterone gel 1.62%?" If you already have enlargement of your prostate gland your signs and symptoms can get worse while using testosterone gel 1.62%. This can include: increased urination at night. trouble starting your urine stream. having to pass urine many times during the day. having an urge to go to the bathroom right away. having a urine accident. being unable to pass urine or weak urine flow. Possible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use testosterone gel 1.62%. Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include leg pain, swelling, or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. Increase in blood pressure. Testosterone gel 1.62% can increase your blood pressure. Increases in blood pressure can increase the risk of heart attack or stroke over time. If your blood pressure increases while on testosterone gel 1.62%, blood pressure medicines may need to be started. If you are taking blood pressure medicines, new blood pressure medicines may need to be added or your current blood pressure medicines may need to be adjusted to control your blood pressure. If your blood pressure cannot be controlled, testosterone gel 1.62% may need to be stopped. Your healthcare provider will monitor your blood pressure while you are being treated with testosterone gel 1.62%. In large doses testosterone gel 1.62% may lower your sperm count. Swelling of your ankles, feet, or body, with or without heart failure. Enlarged or painful breasts. Have problems breathing while you sleep (sleep apnea). Call your healthcare provider right away if you have any of the serious side effects listed above.

In large doses testosterone gel 1.62% may lower your sperm count. Swelling of your ankles, feet, or body, with or without heart failure. Enlarged or painful breasts. Have problems breathing while you sleep (sleep apnea). Call your healthcare provider right away if you have any of the serious side effects listed above. The most common side effects of testosterone gel 1.62% include: increased prostate specific antigen (a test used to screen for prostate cancer) mood swings hypertension increased red blood cell count skin irritation where testosterone gel 1.62% is applied Other side effects include more erections than are normal for you or erections that last a long time. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of testosterone gel 1.62%. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of testosterone gel 1.62% Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use testosterone gel 1.62% for a condition for which it was not prescribed. Do not give testosterone gel 1.62% to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about testosterone gel 1.62% that is written for health professionals. What are the ingredients in testosterone gel 1.62%? Active ingredient: testosterone USP Inactive ingredients: carbomer homopolymer type C, dehydrated alcohol (68.1%w/w), isopropyl myristate, sodium hydroxide and purified water. For more information, call 1-800-399-2561. This Medication Guide has been approved by the U.S. Food and Drug Administration. INSTRUCTIONS FOR USE Testosterone Gel 1.62%, for topical use, CIII (tes TOS ter one) Read this Instructions for Use for testosterone gel 1.62% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment. Applying testosterone gel 1.62%: Testosterone gel 1.62% comes in a pump. Before applying testosterone gel 1.62% make sure that your shoulders and upper arms are clean, dry, and that there is no broken skin. Testosterone gel 1.62% is to be applied to the area of your shoulders and upper arms that will be covered by a short sleeve t-shirt (See Figure A). Do not apply testosterone gel 1.62% to any other parts of your body such as your stomach area (abdomen), penis, scrotum, chest, armpits (axillae), or knees. (Figure A) If you are using testosterone gel 1.62% pump: Before using a new bottle of testosterone gel 1.62 % for the first time, you will need to remove the cap and then prime the pump. To prime the testosterone gel 1.62% pump, slowly push the pump all the way down 3 times, over the sink drain. Do not use any testosterone gel 1.62% that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your testosterone gel 1.62% pump is now ready to use. Remove the cap from the pump. Then, put the spout opening at the top of the pump where the medicine comes out over the palm of your hand and slowly push the pump all the way down. Apply testosterone gel 1.62% to the application site. You may also apply testosterone gel 1.62% directly to the application site. Your healthcare provider will tell you the number of times to press the pump for each dose. Wash your hands with soap and water right away.

ur hand and slowly push the pump all the way down. Apply testosterone gel 1.62% to the application site. You may also apply testosterone gel 1.62% directly to the application site. Your healthcare provider will tell you the number of times to press the pump for each dose. Wash your hands with soap and water right away. Find Your Dose as Prescribed by Your Healthcare Provider Application Method 1 pump 20.25 mg Apply 1 pump of testosterone gel 1.62% to 1 upper arm and shoulder. 2 pumps 40.5 mg Apply 1 pump of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 1 pump of testosterone gel 1.62% to the opposite upper arm and shoulder. 3 pumps 60.75 mg Apply 2 pumps of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 1 pump of testosterone gel 1.62% to the opposite upper arm and shoulder. 4 pumps 81 mg Apply 2 pumps of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 2 pumps of testosterone gel 1.62% to the opposite upper arm and shoulder. How should I store testosterone gel 1.62%? Store testosterone gel 1.62% at room temperature between 68ºF to 77ºF (20ºC to 25ºC). When it is time to throw away the pump, safely throw away used testosterone gel 1.62% in the household trash. Be careful to prevent accidental exposure of children or pets. Keep testosterone gel 1.62% away from fire. Keep testosterone gel 1.62% and all medicines out of the reach of children. This Instructions for Use has been approved by the U.S. Food and Drug Administration. LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc. Manufactured for: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States Manufactured by: Lupin Limited Pithampur (M.P.) – 454 775 India August 2025 ID#: 281571 Figure 1a Figure 1b Image

<table ID="ID220" width="100%" styleCode="Noautorules"><col width="130"/><col width="57"/><col width="450"/><tbody><tr><td colspan="2" valign="top" align="left"><content styleCode="bold"> Find Your Dose as Prescribed by Your Healthcare Provider </content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> Application Method</content> </td></tr><tr><td valign="top" styleCode=" Lrule Botrule Rrule" align="left"> 1 pump </td><td valign="top" styleCode=" Botrule Rrule" align="left"> 20.25 mg </td><td valign="top" styleCode=" Botrule Rrule" align="left"> Apply 1 pump of testosterone gel 1.62% to 1 upper arm and shoulder. </td></tr><tr><td valign="top" styleCode=" Lrule Botrule Rrule" align="left"> 2 pumps </td><td valign="top" styleCode=" Botrule Rrule" align="left"> 40.5 mg </td><td valign="top" styleCode=" Botrule Rrule" align="left"> Apply 1 pump of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 1 pump of testosterone gel 1.62% to the opposite upper arm and shoulder. </td></tr><tr><td valign="top" styleCode=" Lrule Botrule Rrule" align="left"> 3 pumps </td><td valign="top" styleCode=" Botrule Rrule" align="left"> 60.75 mg </td><td valign="top" styleCode=" Botrule Rrule" align="left"> Apply 2 pumps of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 1 pump of testosterone gel 1.62% to the opposite upper arm and shoulder. </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> 4 pumps </td><td valign="top" styleCode=" Botrule Rrule" align="left"> 81 mg </td><td valign="top" styleCode=" Botrule Rrule" align="left"> Apply 2 pumps of testosterone gel 1.62% to 1 upper arm and shoulder and then apply 2 pumps of testosterone gel 1.62% to the opposite upper arm and shoulder. </td></tr></tbody></table>

Warnings and Precautions, Venous Thromboembolism ( 5.3 ) 07/2025 Warnings and Precautions, Blood Pressure Increases ( 5.5 ) 07/2025 Warnings and Precautions, Cardiovascular Risk ( 5.5 ) Removed 07/2025

WARNING: SECONDARY EXPOSURE TO TESTOSTERONE ▪ Virilization has been reported in children who were secondarily exposed to testosterone gel [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.2 )] . ▪ Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel [see Dosage and Administration ( 2.2 ) and Warnings and Precautions ( 5.1 )] . ▪ Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 ) and Patient Counseling Information ( 17 )] . WARNING: SECONDARY EXPOSURE TO TESTOSTERONE See full prescribing information for complete boxed warning. ▪ Virilization has been reported in children who were secondarily exposed to testosterone gel ( 5.2 , 6.2 ). ▪ Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel ( 2.2 , 5.2 ). ▪ Healthcare providers should advise patients to strictly adhere to recommended instructions for use ( 2.2 , 5.2 , 17 ).

1 INDICATIONS AND USAGE Testosterone Gel, 1.62% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: • Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. • Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range. Limitations of use: • Safety and efficacy of Testosterone Gel, 1.62% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. • Safety and efficacy of Testosterone Gel, 1.62% in males less than 18 years old have not been established [see Use in Specific Populations (8.4) ] . • Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see Indications and Usage (1) , and Clinical Pharmacology (12.3) ] . Testosterone Gel, 1.62% is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: • Primary hypogonadism (congenital or acquired) ( 1 ) • Hypogonadotropic hypogonadism (congenital or acquired) ( 1 ) Limitations of use: • Safety and efficacy of Testosterone Gel, 1.62% in men with “age-related hypogonadism” have not been established. ( 1 ) • Safety and efficacy of Testosterone Gel, 1.62% in males less than 18 years old have not been established. ( 1 , 8.4 ) • Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure. ( 1 , 12.3 )

2 DOSAGE AND ADMINISTRATION Dosage and Administration for Testosterone Gel, 1.62% differs from Testosterone Gel, 1%. For dosage and administration of Testosterone Gel, 1% refer to its full prescribing information. ( 2 ) Prior to initiating Testosterone Gel, 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. • Dosage and Administration for Testosterone Gel, 1.62% differs from Testosterone Gel, 1%. For dosage and administration of Testosterone Gel, 1% refer to its full prescribing information. ( 2 ) • Prior to initiating Testosterone Gel, 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range. ( 2 ) • Starting dose of Testosterone Gel, 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet), applied topically once daily in the morning. ( 2.1 ) • Apply to clean, dry, intact skin of the shoulders and upper arms. Do not apply Testosterone Gel, 1.62% to any other parts of the body including the abdomen, genitals, chest, armpits (axillae), or knees. ( 2.2 , 12.3 ) • Dose adjustment: Testosterone Gel, 1.62% can be dose adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation or a single 20.25 mg packet) and a maximum of 81 mg of testosterone (4 pump actuations or two 40.5 mg packets). The dose should be titrated based on the pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment or following dose adjustment. Additionally, serum testosterone concentration should be assessed periodically thereafter. ( 2.1 ) • Patients should wash their hands immediately with soap and water after applying Testosterone Gel, 1.62% and cover the application site(s) with clothing after the gel has dried. Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated. ( 2.2 ) 2.1 Dosing and Dose Adjustment The recommended starting dose of Testosterone Gel, 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning to the shoulders and upper arms. The dose can be adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation or a single 20.25 mg packet) and a maximum of 81 mg of testosterone (4 pump actuations or two 40.5 mg packets). To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step.

morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step. Table 1: Dose Adjustment Criteria Pre-Dose Morning Total Serum Testosterone Concentration Dose Titration Greater than 750 ng/dL Decrease daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet) Equal to or greater than 350 and equal to or less than 750 ng/dL No change: continue on current dose Less than 350 ng/dL Increase daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet) The application site and dose of Testosterone Gel, 1.62% are not substitutable-with other topical testosterone products. 2.2 Administration Instructions Testosterone Gel, 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply Testosterone Gel, 1.62% to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees [see Clinical Pharmacology (12.3) ] . Area of application should be limited to the area that will be covered by the patient’s short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply Testosterone Gel, 1.62% and spread across the maximum surface area as directed in Table 2 (for pump) and Table 3 (for packets) and in Figure 1. Table 2: Application Sites for Testosterone Gel, 1.62%, Pump Total Dose of Testosterone Total Pump Actuations Pump Actuations Per Upper Arm and Shoulder Upper Arm and Shoulder #1 Upper Arm and Shoulder #2 20.25 mg 1 1 0 40.5 mg 2 1 1 60.75 mg 3 2 1 81 mg 4 2 2 Table 3: Application Sites for Testosterone Gel, 1.62%, Packets Total Dose of Testosterone Total packets Gel Applications Per Upper Arm and Shoulder Upper Arm and Shoulder #1 Upper Arm and Shoulder #2 20.25 mg One 20.25 mg packet One 20.25 mg packet 0 40.5 mg One 40.5 mg packet Half of contents of One 40.5 mg packet Half of contents of One 40.5 mg packet 60.75 mg One 20.25 mg packet AND One 40.5 mg packet One 40.5 mg packet One 20.25 mg packet 81 mg Two 40.5 mg packets One 40.5 mg packet One 40.5 mg packet The prescribed daily dose of Testosterone Gel, 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1. Figure 1. Application Sites for Testosterone Gel, 1.62% Once the application site is dry, the site should be covered with clothing [ see Clinical Pharmacology (12.3) ]. Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including Testosterone Gel, 1.62%, are flammable. The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see Clinical Pharmacology (12.3) ] . To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose. After the priming procedure, fully depress the actuator once for every 20.25 mg of Testosterone Gel, 1.62%. Testosterone Gel, 1.62% should be delivered directly into the palm of the hand and then applied to the application sites. When using packets, the entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. When 40.5 mg packets need to be split between the left and right shoulder, patients may squeeze a portion of the gel from the packet into the palm of the hand and apply to application sites.

using packets, the entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. When 40.5 mg packets need to be split between the left and right shoulder, patients may squeeze a portion of the gel from the packet into the palm of the hand and apply to application sites. Repeat until entire contents have been applied. Alternatively, Testosterone Gel, 1.62% can be applied directly to the application sites from the pump or packets. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from Testosterone Gel, 1.62%-treated skin: • Children and women should avoid contact with unwashed or unclothed application site(s) of men using Testosterone Gel, 1.62%. • Testosterone Gel, 1.62% should only be applied to the upper arms and shoulders. The area of application should be limited to the area that will be covered by a short sleeve t-shirt. • Patients should wash their hands with soap and water immediately after applying Testosterone Gel, 1.62%. • Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried. • Prior to situations in which direct skin-to-skin contact is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue. • In the event that unwashed or unclothed skin to which Testosterone Gel, 1.62% has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible. Figure 1

3 DOSAGE FORMS AND STRENGTHS Testosterone Gel, 1.62% for topical use only, is available as follows: • A metered-dose pump. Each pump actuation delivers 20.25 mg of testosterone in 1.25 g of gel. • A unit dose packet containing 20.25 mg of testosterone in 1.25 g of gel. • A unit dose packet containing 40.5 mg of testosterone in 2.5 g of gel. Testosterone Gel, 1.62% for topical use is available as follows: • a metered-dose pump that delivers 20.25 mg testosterone per actuation. ( 3 ) • packets containing 20.25 mg testosterone. ( 3 ) • packets containing 40.5 mg testosterone. ( 3 )

4 CONTRAINDICATIONS • Testosterone Gel, 1.62% is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . • Testosterone Gel, 1.62% is contraindicated in women who are pregnant. Testosterone Gel, 1.62% can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women need to be aware of the potential for transfer of testosterone from men treated with Testosterone Gel, 1.62%. If a pregnant woman is exposed to Testosterone Gel, 1.62%, she should be apprised of the potential hazard to the fetus [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1) ]. • Men with carcinoma of the breast or known or suspected prostate cancer ( 4 , 5.1 ) • Women who are pregnant. Testosterone may cause fetal harm ( 4 , 8.1 )

5 WARNINGS AND PRECAUTIONS • Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer: Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. ( 5.1 ) • Potential for Secondary Exposure to Testosterone: Avoid unintentional exposure of women or children to Testosterone Gel, 1.62%. Secondary exposure to testosterone can produce signs of virilization. Testosterone Gel, 1.62% should be discontinued until the cause of virilization is identified. ( 5.2 ) • Venous Thromboembolism (VTE): VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Evaluate patients with signs or symptoms consistent with DVT or PE. ( 5.4 ) • Blood Pressure Increases: Testosterone Gel, 1.62% can increase blood pressure, which can increase cardiovascular risk over time. Measure blood pressure periodically. Not recommended for use in men with uncontrolled hypertension. ( 5.5 ) • Potential for Adverse Effects on Spermatogenesis: Exogenous administration of androgens may lead to azoospermia. ( 5.8 ) • Edema: Edema, with or without congestive heart failure (CHF), may be a complication in patients with preexisting cardiac, renal, or hepatic disease. ( 5.10 , 6.2 ) • Sleep apnea: Sleep apnea may occur in those with risk factors. ( 5.12 ) • Monitor serum testosterone, prostate specific antigen (PSA), hemoglobin, hematocrit, liver function tests, and lipid concentrations periodically. ( 5.1 , 5.3 , 5.9 , 5.13 ) • Flammability: Testosterone Gel, 1.62% is flammable until dry. ( 5.16 ) 5.1 Potential for Secondary Exposure to Testosterone Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using Testosterone Gel, 1.62% [see Dosage and Administration (2.2) , Use in Specific Populations (8.1) and Clinical Pharmacology (12.3) ] . Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified. 5.2 Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration.

quire lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events. 5.3 Venous Thromboembolism There have been postmarketing reports of venous thromboembolic events (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products such as Testosterone Gel, 1.62%. In the Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) Study, a randomized, double-blind, placebo-controlled, cardiovascular (CV) outcomes study, compared to placebo, Testosterone Gel, 1.62% was associated with a numerically higher incidence of VTE (1.7% vs 1.2%) which included DVT (0.6% vs 0.5%) and PE events (0.9% vs 0.5%) [see Adverse Reactions (6.1) ]. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with Testosterone Gel, 1.62% and initiate appropriate workup and management [see Adverse Reactions (6.2) ] . 5.4 Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer • Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. • Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [see Contraindications (4) , Adverse Reactions (6.1) and Nonclinical Toxicology (13.1) ] . 5.5 Blood Pressure Increases Testosterone Gel, 1.62% can increase blood pressure. In an ambulatory blood pressure monitoring (ABPM) study, Testosterone Gel, 1.62% increased the mean systolic/diastolic blood pressure by 1.9/1.3 mm Hg from baseline after 16 weeks of treatment. In patients with hypertension on antihypertensive therapy, Testosterone Gel, 1.62% increased the mean systolic/diastolic BP by 3.0/2.2 mm Hg from baseline. Blood pressure increases can increase cardiovascular (CV) risk over time. The CV risk associated with Testosterone Gel, 1.62% was evaluated in TRAVERSE, a randomized, double-blind, placebo-controlled, CV outcomes study in men with a history of CV disease or multiple CV risk factors. In TRAVERSE, mean systolic blood pressure in the group treated with Testosterone Gel,1.62% increased by 1.0 mm Hg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 mm Hg was observed in the placebo group at this timepoint, for a mean between-group difference of 1.5 mm Hg. However, the incidences of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction [MI] and non-fatal stroke, were similar between treatment groups (7% for Testosterone Gel, 1.62% vs 7.3% for placebo) [see Adverse Reactions (6.1) ] . Monitor blood pressure periodically in men using Testosterone Gel, 1.62%, especially men with hypertension. Testosterone Gel, 1.62% is not recommended for use in patients with uncontrolled hypertension. 5.6 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids.

is not recommended for use in patients with uncontrolled hypertension. 5.6 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence (9) ] . If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. 5.7 Not for Use in Women Due to the lack of controlled evaluations in women and potential virilizing effects, Testosterone Gel, 1.62% is not indicated for use in women [see Contraindications (4) and Use in Specific Populations (8.1 , 8.2) ] . 5.8 Potential for Adverse Effects on Spermatogenesis With large doses of exogenous androgens, including Testosterone Gel, 1.62%, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH possibly leading to adverse effects on semen parameters including sperm count. 5.9 Hepatic Adverse Effects Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. Testosterone Gel, 1.62% is not known to cause these adverse effects. 5.10 Edema Androgens, including Testosterone Gel, 1.62%, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease [see Adverse Reactions (6.2) ] . 5.11 Gynecomastia Gynecomastia may develop and persist in patients being treated with androgens, including Testosterone Gel, 1.62%, for hypogonadism. 5.12 Sleep Apnea The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. 5.13 Lipid Changes Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy, such as Testosterone Gel, 1.62%. Monitor the lipid profile periodically, particularly after starting testosterone therapy. 5.14 Hypercalcemia Androgens, including Testosterone Gel, 1.62%, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. 5.15 Decreased Thyroxine-binding Globulin Androgens, including Testosterone Gel, 1.62%, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. 5.16 Flammability Alcohol based products, including Testosterone Gel, 1.62%, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the Testosterone Gel, 1.62% has dried.

6 ADVERSE REACTIONS The most common adverse reaction (incidence ≥ 5%) is an increase in prostate specific antigen (PSA). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Testosterone gel, 1.62% was evaluated in a two-phase, 364-day, controlled clinical study. The first phase was a multi-center, randomized, double-blind, parallel-group, placebo-controlled period of 182 days, in which 234 hypogonadal men were treated with testosterone gel, 1.62% and 40 received placebo. Patients could continue in an open-label, non-comparative, maintenance period for an additional 182 days [ see Clinical Studies (14.1) ]. The most common adverse reaction reported in the double-blind period was increased prostate specific antigen (PSA) reported in 26 testosterone gel, 1.62%-treated patients (11.1%). In 17 patients, increased PSA was considered an adverse event by meeting one of the two pre-specified criteria for abnormal PSA values, defined as (1) average serum PSA >4 ng/mL based on two separate determinations, or (2) an average change from baseline in serum PSA of greater than 0.75 ng/mL on two determinations. During the 182-day, double-blind period of the clinical trial, the mean change in serum PSA value was 0.14 ng/mL for patients receiving testosterone gel, 1.62% and -0.12 ng/mL for the patients in the placebo group. During the double-blind period, seven patients had a PSA value >4.0 ng/mL, four of these seven patients had PSA less than or equal to 4.0 ng/mL upon repeat testing. The other three patients did not undergo repeat PSA testing. During the 182-day, open-label period of the study, the mean change in serum PSA values was 0.10 ng/mL for both patients continuing on active therapy and patients transitioning onto active from placebo. During the open-label period, three patients had a serum PSA value > 4.0 ng/mL, two of whom had a serum PSA less than or equal to 4.0 ng/mL upon repeated testing. The other patient did not undergo repeat PSA testing. Among previous placebo patients, 3 of 28 (10.7%), had increased PSA as an adverse event in the open-label period. Table 4 shows adverse reactions reported by >2% of patients in the 182-day, double-blind period of the testosterone gel, 1.62% clinical trial and more frequent in the testosterone gel, 1.62% treated group versus placebo. Table 4: Adverse Reactions Reported in >2% of Patients in the 182-Day, Double-Blind Period of Testosterone Gel, 1.62% Clinical Trial Number (%) of Patients Adverse Reaction Testosterone Gel, 1.62% N=234 Placebo N=40 PSA increased* 26 (11.1%) 0% Emotional lability** 6 (2.6%) 0% Hypertension 5 (2.1%) 0% Hematocrit or hemoglobin increased 5 (2.1%) 0% Contact dermatitis*** 5 (2.1%) 0% * PSA increased includes: PSA values that met pre-specified criteria for abnormal PSA values (an average change from baseline > 0.75 ng/mL and/or an average PSA value >4.0 ng/mL based on two measurements) as well as those reported as adverse events. ** Emotional lability includes: mood swings, affective disorder, impatience, anger, and aggression.

values that met pre-specified criteria for abnormal PSA values (an average change from baseline > 0.75 ng/mL and/or an average PSA value >4.0 ng/mL based on two measurements) as well as those reported as adverse events. ** Emotional lability includes: mood swings, affective disorder, impatience, anger, and aggression. *** Contact dermatitis includes: 4 patients with dermatitis at non-application sites. Other adverse reactions occurring in less than or equal to 2% of testosterone gel, 1.62%-treated patients and more frequently than placebo included: frequent urination, and hyperlipidemia. In the open-label period of the study (N=191), the most commonly reported adverse reaction (experienced by greater than 2% of patients) was increased PSA (n=13; 6.2%) and sinusitis. Other adverse reactions reported by less than or equal to 2% of patients included increased hemoglobin or hematocrit, hypertension, acne, libido decreased, insomnia, and benign prostatic hypertrophy. During the 182-day, double-blind period of the clinical trial, 25 testosterone gel, 1.62%-treated patients (10.7%) discontinued treatment because of adverse reactions. These adverse reactions included 17 patients with PSA increased and 1 report each of: hematocrit increased, blood pressure increased, frequent urination, diarrhea, fatigue, pituitary tumor, dizziness, skin erythema and skin nodule (same patient – neither at application site), vasovagal syncope, and diabetes mellitus. During the 182-day, open-label period, 9 patients discontinued treatment because of adverse reactions. These adverse reactions included 6 reports of PSA increased, 2 of hematocrit increased, and 1 each of triglycerides increased and prostate cancer. Application Site Reactions In the 182-day double-blind period of the study, application site reactions were reported in two (2/234; 0.9%) patients receiving testosterone gel, 1.62%, both of which resolved. Neither of these patients discontinued the study due to application site adverse reactions. In the open-label period of the study, application site reactions were reported in three (3/219; 1.4%) additional patients that were treated with testosterone gel, 1.62%. None of these subjects were discontinued from the study due to application site reactions. Blood Pressure Increases In a 4-month clinical study, 24-hour ambulatory blood pressure monitoring (ABPM) was conducted on 246 patients. ABPM was conducted at baseline and at Week 16 of testosterone gel, 1.62% therapy. A total of 169 patients had acceptable ABPM recordings at both baseline and Week 16 and were at least 85% compliant with study drug. In that group, the mean change in 24-hour systolic blood pressure (BP) and diastolic BP from baseline to end-of-treatment at Week 16 (n=169) was 1.9 mm Hg (95% CI 0.6, 3.1) and 1.3 mm Hg (95% CI 0.5, 2.1), respectively. In patients with a history of hypertension who were receiving antihypertensive therapy, the mean ABPM systolic and diastolic BP increased by 3.0 mm Hg [95% CI 0.8, 5.2] and 2.2 mm Hg [95% CI 0.8, 3.5], respectively [n=72]). In patients with no history of hypertension, the mean systolic and diastolic blood pressure increased by 1.2 mm Hg [95% CI -0.2, 2.7] and 0.9 mm Hg [95% CI -0.1, 1.8], respectively [n=91]. Four patients (2.8%) on testosterone gel, 1.62%, all of whom were receiving antihypertensive medications at baseline, either started new antihypertensive medications (n=2) or had their antihypertensive medication regimen adjusted (n=2) during the ABPM study. Of the 246 patients in the ABPM study who used testosterone gel, 1.62%, 10 patients (4.1%) were reported to have either an adverse reaction of hypertension (5 patients, 2.0%) or increased blood pressure (5 patients, 2.0%).

ions (n=2) or had their antihypertensive medication regimen adjusted (n=2) during the ABPM study. Of the 246 patients in the ABPM study who used testosterone gel, 1.62%, 10 patients (4.1%) were reported to have either an adverse reaction of hypertension (5 patients, 2.0%) or increased blood pressure (5 patients, 2.0%). Cardiovascular Outcomes TRAVERSE was a randomized, double-blind, cardiovascular outcomes study to assess the cardiovascular (CV) safety of testosterone gel, 1.62% compared to placebo in 5198 hypogonadal men aged 45 to 80 years with a history of CV disease or with multiple CV risk factors. The primary outcome was the incidence of the composite endpoint of major adverse cardiovascular events (MACE), consisting of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. The mean duration of therapy was approximately 22 months. The mean duration of follow-up was 33 months. Approximately 61% of all patients discontinued testosterone gel, 1.62% or placebo therapy. The mean (±SD) daily dose of testosterone was 65±22 mg. The mean patient age (±SD) was 63.3 (7.9) years, with 2452 patients aged 65 years or more (47%); 2847 (about 55%) patients had pre-existing cardiovascular disease, whereas 2357 (about 45%) patients had an elevated cardiovascular risk at baseline, and mean BMI was 35kg/m 2 . Approximately 80% of patients were White, 17% were Black, and 3% were of other races or ethnic groups. Approximately 69%, 84%, and 93% had diabetes mellitus, hyperlipidemia, and hypertension, respectively. The mean serum testosterone concentration at baseline in patients receiving testosterone gel, 1.62% was 220.4 ng/dL (n=2596). The mean serum testosterone concentrations at 12 months, 24 months, 36 months, and 48 months in patients receiving testosterone gel, 1.62% were 440.5 ng/dL (n=1683), 420.9 ng/dl (n=1125), 428.7 ng/dL (n=731), and 365.2 ng/dL (n=220), respectively. For patients treated with testosterone gel, 1.62%, the incidence of MACE was 7.0% (n=182 events) and for those receiving placebo, the incidence of MACE was 7.3% (n=190 events). The study demonstrated non-inferiority of testosterone gel, 1.62% versus placebo because the upper bound of 95% CI was less than the pre-specified risk margin, of 1.5 for MACE (Hazard Ratio 0.96 [95% CI: 0.78, 1.17]). Additional Adverse Reactions Reported in TRAVERSE Additional adverse reactions reported in TRAVERSE at an incidence rate >2% in either treatment group and greater in testosterone gel, 1.62% versus placebo included: nonfatal arrythmias warranting intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and bone fracture (3.5% vs 2.5%). For the adverse reaction of bone fracture, each event was adjudicated by clinical review. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of testosterone gel, 1.62%. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 5).

ence The following adverse reactions have been identified during post approval use of testosterone gel, 1.62%. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 5). Table 5: Adverse Reactions from Post Approval Experience of Testosterone Gel, 1.62% by System Organ Class System Organ Class Adverse Reaction Blood and lymphatic system disorders: Elevated hemoglobin or hematocrit, polycythemia, anemia Cardiovascular disorders: Myocardial infarction, stroke Endocrine disorders: Hirsutism Gastrointestinal disorders: Nausea General disorders: Asthenia, edema, malaise Genitourinary disorders: Impaired urination* Hepatobiliary disorders: Abnormal liver function tests Investigations: Lab test abnormal**, elevated PSA, electrolyte changes (nitrogen, calcium, potassium [includes hypokalemia], phosphorus, sodium), impaired glucose tolerance, hyperlipidemia, HDL, fluctuating testosterone levels, weight increase Neoplasms: Prostate cancer Nervous system disorders: Dizziness, headache, insomnia, sleep apnea Psychiatric disorders: Amnesia, anxiety, depression, hostility, emotional lability, decreased libido, nervousness Reproductive system and breast disorders: Gynecomastia, mastodynia, oligospermia, priapism (frequent or prolonged erections), prostate enlargement, BPH, testis disorder*** Respiratory disorders: Dyspnea Skin and subcutaneous tissue disorders: Acne, alopecia, application site reaction (discolored hair, dry skin, erythema, paresthesia, pruritus, rash), skin dry, pruritus, sweating Vascular disorders: Hypertension, vasodilation (hot flushes), venous thromboembolism * Impaired urination includes nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream ** Lab test abnormal includes elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, or elevated serum creatinine *** Testis disorder includes atrophy or non-palpable testis, varicocele, testis sensitivity or tenderness Secondary Exposure to Testosterone in Children Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirts and/or other fabric, such as towels and sheets [see Warnings and Precautions (5.2) ] .

<table width="100%"><col width="38%"/><col width="36%"/><col width="18%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"/><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Number (%) of Patients</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Testosterone Gel, 1.62%</content></paragraph><paragraph><content styleCode="bold"> N=234</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo</content></paragraph><paragraph><content styleCode="bold">N=40</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>PSA increased*</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>26 (11.1%)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Emotional lability**</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6 (2.6%)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hypertension</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5 (2.1%)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hematocrit or hemoglobin increased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5 (2.1%)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Contact dermatitis***</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5 (2.1%)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0%</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>*<content styleCode="bold"><content styleCode="italics">PSA increased </content></content>includes: PSA values that met pre-specified criteria for abnormal PSA values (an average change from baseline &gt; 0.75 ng/mL and/or an average PSA value &gt;4.0 ng/mL based on two measurements) as well as those reported as adverse events.</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>**<content styleCode="bold"><content styleCode="italics">Emotional lability </content></content>includes: mood swings, affective disorder, impatience, anger, and aggression.</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>***<content styleCode="bold"><content styleCode="italics">Contact dermatitis </content></content>includes: 4 patients with dermatitis at non-application sites.</paragraph></td></tr></tbody></table>

and aggression.</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>***<content styleCode="bold"><content styleCode="italics">Contact dermatitis </content></content>includes: 4 patients with dermatitis at non-application sites.</paragraph></td></tr></tbody></table> <table width="100%"><col width="50%"/><col width="50%"/><tbody><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">System Organ Class</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Blood and lymphatic system disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Elevated hemoglobin or hematocrit, polycythemia, anemia</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Cardiovascular disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Myocardial infarction, stroke</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Endocrine disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Hirsutism</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Nausea</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Asthenia, edema, malaise</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Genitourinary disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Impaired urination*</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Hepatobiliary disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Abnormal liver function tests</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Investigations:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Lab test abnormal**, elevated PSA, electrolyte changes (nitrogen, calcium, potassium [includes hypokalemia], phosphorus, sodium), impaired glucose tolerance, hyperlipidemia, HDL, fluctuating testosterone levels, weight increase</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Neoplasms:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Prostate cancer</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Dizziness, headache, insomnia, sleep apnea</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Psychiatric disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Amnesia, anxiety, depression, hostility, emotional lability, decreased libido, nervousness</paragraph></td></tr><tr><td styleCode="Rrule Lrul

Botrule " valign="top"><paragraph><content styleCode="bold">Psychiatric disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Amnesia, anxiety, depression, hostility, emotional lability, decreased libido, nervousness</paragraph></td></tr><tr><td styleCode="Rrule Lrul e Botrule " valign="top"><paragraph><content styleCode="bold">Reproductive system and breast disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Gynecomastia, mastodynia, oligospermia, priapism (frequent or prolonged erections), prostate enlargement, BPH, testis disorder***</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Respiratory disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Dyspnea</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Skin and subcutaneous tissue disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Acne, alopecia, application site reaction (discolored hair, dry skin, erythema, paresthesia, pruritus, rash), skin dry, pruritus, sweating</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Vascular disorders:</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Hypertension, vasodilation (hot flushes), venous thromboembolism</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>* <content styleCode="bold"><content styleCode="italics">Impaired urination </content>includes </content>nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>**<content styleCode="bold"><content styleCode="italics">Lab test abnormal </content>includes </content>elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, or elevated serum creatinine</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>***<content styleCode="bold"><content styleCode="italics">Testis disorder </content>includes </content>atrophy or non-palpable testis, varicocele, testis sensitivity or tenderness</paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS • Androgens may decrease blood glucose and therefore may decrease insulin requirements in diabetic patients ( 7.1 ) • Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended ( 7.2 ) • Use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease ( 7.3 ) 7.1 Insulin Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease insulin requirements. 7.2 Oral Anticoagulants Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy. 7.3 Corticosteroids The concurrent use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.

8 USE IN SPECIFIC POPULATIONS There are insufficient long-term safety data in geriatric patients using Testosterone Gel, 1.62% to assess the potential risks of cardiovascular disease and prostate cancer. ( 8.5 ) 8.1 Pregnancy Risk Summary Testosterone Gel, 1.62% is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology (12.1) ] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes. Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy. 8.2 Lactation Risk Summary Testosterone Gel, 1.62% is not indicated for use in women. 8.3 Females and Males of Reproductive Potential Infertility Testis disorder, testicular atrophy, and oligospermia have been identified during use of Testosterone Gel, 1.62% [see Adverse Reactions (6.1 , 6.2) ] . During treatment with large doses of exogenous androgens, including Testosterone Gel, 1.62%, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions (5.8) ] . Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see Drug Abuse and Dependence (9.2) ] . With either type of use, the impact on fertility may be irreversible. 8.4 Pediatric Use The safety and effectiveness of testosterone gel, 1.62% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses. 8.5 Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel, 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing testosterone gel, 1.62%, 21 were over 65 years of age.

ufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel, 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing testosterone gel, 1.62%, 21 were over 65 years of age. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer. Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH. 8.6 Renal Impairment No studies were conducted involving patients with renal impairment. 8.7 Hepatic Impairment No studies were conducted in patients with hepatic impairment.

8.1 Pregnancy Risk Summary Testosterone Gel, 1.62% is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology (12.1) ] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes. Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy.

8.3 Females and Males of Reproductive Potential Infertility Testis disorder, testicular atrophy, and oligospermia have been identified during use of Testosterone Gel, 1.62% [see Adverse Reactions (6.1 , 6.2) ] . During treatment with large doses of exogenous androgens, including Testosterone Gel, 1.62%, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions (5.8) ] . Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see Drug Abuse and Dependence (9.2) ] . With either type of use, the impact on fertility may be irreversible.

8.4 Pediatric Use The safety and effectiveness of testosterone gel, 1.62% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

8.5 Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel, 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing testosterone gel, 1.62%, 21 were over 65 years of age. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer. Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH.

9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance Testosterone Gel, 1.62% contains testosterone, a Schedule III controlled substance in the Controlled Substances Act. 9.2 Abuse Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice. Abuse-Related Adverse Reactions Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression. The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility. The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty. Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 9.3 Dependence Behaviors Associated with Addiction Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors: • Taking greater dosages than prescribed • Continued drug use despite medical and social problems due to drug use • Spending significant time to obtain the drug when supplies of the drug are interrupted • Giving a higher priority to drug use than other obligations • Having difficulty in discontinuing the drug despite desires and attempts to do so • Experiencing withdrawal symptoms upon abrupt discontinuation of use Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

9.3 Dependence Behaviors Associated with Addiction Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors: • Taking greater dosages than prescribed • Continued drug use despite medical and social problems due to drug use • Spending significant time to obtain the drug when supplies of the drug are interrupted • Giving a higher priority to drug use than other obligations • Having difficulty in discontinuing the drug despite desires and attempts to do so • Experiencing withdrawal symptoms upon abrupt discontinuation of use Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

10 OVERDOSAGE There is a single report of acute overdosage after parenteral administration of an approved testosterone product in the literature. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident. There were no reports of overdosage in the testosterone gel, 1.62% clinical trial. Treatment of overdosage would consist of discontinuation of Testosterone Gel, 1.62%, washing the application site with soap and water, and appropriate symptomatic and supportive care.

11 DESCRIPTION Testosterone Gel, 1.62% for topical use is a clear, colorless gel containing testosterone. Testosterone is an androgen. Testosterone Gel, 1.62% is available in a metered-dose pump or unit dose packets. The active pharmacologic ingredient in Testosterone Gel, 1.62% is testosterone. Testosterone USP is a white to almost white powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is: The inactive ingredients in Testosterone Gel, 1.62% are: carbopol 980, ethyl alcohol, isopropyl myristate, purified water, and sodium hydroxide. Chemical Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement; vocal cord thickening; and alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). 12.2 Pharmacodynamics No specific pharmacodynamic studies were conducted using testosterone gel, 1.62%. 12.3 Pharmacokinetics Absorption Testosterone gel, 1.62% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (300 – 1000 ng/dL) seen in healthy men. Testosterone gel, 1.62% provides continuous topical delivery of testosterone for 24 hours following once daily application to clean, dry, intact skin of the shoulders and upper arms. Average serum testosterone concentrations over 24 hours (C avg ) observed when testosterone gel, 1.62% was applied to the upper arms/shoulders were comparable to average serum testosterone concentrations (C avg ) when testosterone gel, 1.62% was applied using a rotation method utilizing the abdomen and upper arms/shoulders. The rotation of abdomen and upper arms/shoulders was a method used in the pivotal clinical trial [ see Clinical Studies (14.1) ]. Figure 2: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients Following Testosterone Gel, 1.62% Once-Daily Application of 81 mg of Testosterone (N=33) for 7 Days Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT. Excretion There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. When testosterone gel, 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48-72 hours after administration of the last dose.

dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. When testosterone gel, 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48-72 hours after administration of the last dose. Potential for testosterone transfer The potential for testosterone transfer following administration of testosterone gel, 1.62% when it was applied only to upper arms/shoulders was evaluated in two clinical studies of males dosed with testosterone gel, 1.62% and their untreated female partners. In one study, 8 male subjects applied a single dose of testosterone gel, 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes. Serum concentrations of testosterone were monitored in female subjects for 24 hours after contact occurred. After direct skin-to-skin contact with the site of application, mean testosterone C avg and C max in female subjects increased by 280% and 267%, respectively, compared to mean baseline testosterone concentrations. In a second study evaluating transfer of testosterone, 12 male subjects applied a single dose of testosterone gel, 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt. When a t-shirt was used to cover the site of application, mean testosterone C avg and C max in female subjects increased by 6% and 11%, respectively, compared to mean baseline testosterone concentrations. A separate study was conducted to evaluate the potential for testosterone transfer from 16 males dosed with testosterone gel, 1.62% 81 mg when it was applied to abdomen only for 7 days, a site of application not approved for testosterone gel, 1.62%. Two (2) hours after application to the males on each day, the female subjects rubbed their abdomens for 15 minutes to the abdomen of the males. The males had covered the application area with a T-shirt. The mean testosterone C avg and C max in female subjects on day 1 increased by 43% and 47%, respectively, compared to mean baseline testosterone concentrations. The mean testosterone C avg and C max in female subjects on day 7 increased by 60% and 58%, respectively, compared to mean baseline testosterone concentrations. Effect of showering In a randomized, 3-way (3 treatment periods without washout period) crossover study in 24 hypogonadal men, the effect of showering on testosterone exposure was assessed after once daily application of testosterone gel, 1.62% 81 mg to upper arms/shoulders for 7 days in each treatment period. On the 7th day of each treatment period, hypogonadal men took a shower with soap and water at either 2, 6, or 10 hours after drug application. The effect of showering at 2 or 6 hours post-dose on Day 7 resulted in 13% and 12% decreases in mean C avg , respectively, compared to Day 6 when no shower was taken after drug application. Showering at 10 hours after drug application had no effect on bioavailability. The amount of testosterone remaining in the outer layers of the skin at the application site on the 7th day was assessed using a tape stripping procedure and was reduced by at least 80% after showering 2-10 hours post-dose compared to on the 6th day when no shower was taken after drug application. Effect of hand washing In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated.

ter showering 2-10 hours post-dose compared to on the 6th day when no shower was taken after drug application. Effect of hand washing In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated. Subjects used their hands to apply the maximum dose (81 mg testosterone) of testosterone gel, 1.62% to their upper arms and shoulders. Within 1 minute of applying the gel, subjects either washed or did not wash their hands prior to study personnel wiping the subjects’ hands with ethanol dampened gauze pads. The gauze pads were then analyzed for residual testosterone content. A mean (SD) of 0.1 (0.04) mg of residual testosterone (0.12% of the actual applied dose of testosterone, and a 96% reduction compared to when hands were not washed) was recovered after washing hands with water and soap. Effect of sunscreen or moisturizing lotion on absorption of testosterone In a randomized, 3-way (3 treatment periods without washout period) crossover study in 18 hypogonadal males, the effect of applying a moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the testosterone gel, 1.62% application site 1 hour after the application of testosterone gel, 1.62% 40.5 mg. Application of moisturizing lotion increased mean testosterone C avg and C max by 14% and 17%, respectively, compared to testosterone gel, 1.62% administered alone. Application of sunscreen increased mean testosterone C avg and C max by 8% and 13%, respectively, compared to testosterone gel, 1.62% applied alone. Figure-2

12.3 Pharmacokinetics Absorption Testosterone gel, 1.62% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (300 – 1000 ng/dL) seen in healthy men. Testosterone gel, 1.62% provides continuous topical delivery of testosterone for 24 hours following once daily application to clean, dry, intact skin of the shoulders and upper arms. Average serum testosterone concentrations over 24 hours (C avg ) observed when testosterone gel, 1.62% was applied to the upper arms/shoulders were comparable to average serum testosterone concentrations (C avg ) when testosterone gel, 1.62% was applied using a rotation method utilizing the abdomen and upper arms/shoulders. The rotation of abdomen and upper arms/shoulders was a method used in the pivotal clinical trial [ see Clinical Studies (14.1) ]. Figure 2: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients Following Testosterone Gel, 1.62% Once-Daily Application of 81 mg of Testosterone (N=33) for 7 Days Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT. Excretion There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. When testosterone gel, 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48-72 hours after administration of the last dose. Potential for testosterone transfer The potential for testosterone transfer following administration of testosterone gel, 1.62% when it was applied only to upper arms/shoulders was evaluated in two clinical studies of males dosed with testosterone gel, 1.62% and their untreated female partners. In one study, 8 male subjects applied a single dose of testosterone gel, 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes. Serum concentrations of testosterone were monitored in female subjects for 24 hours after contact occurred. After direct skin-to-skin contact with the site of application, mean testosterone C avg and C max in female subjects increased by 280% and 267%, respectively, compared to mean baseline testosterone concentrations. In a second study evaluating transfer of testosterone, 12 male subjects applied a single dose of testosterone gel, 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt.

12 male subjects applied a single dose of testosterone gel, 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt. When a t-shirt was used to cover the site of application, mean testosterone C avg and C max in female subjects increased by 6% and 11%, respectively, compared to mean baseline testosterone concentrations. A separate study was conducted to evaluate the potential for testosterone transfer from 16 males dosed with testosterone gel, 1.62% 81 mg when it was applied to abdomen only for 7 days, a site of application not approved for testosterone gel, 1.62%. Two (2) hours after application to the males on each day, the female subjects rubbed their abdomens for 15 minutes to the abdomen of the males. The males had covered the application area with a T-shirt. The mean testosterone C avg and C max in female subjects on day 1 increased by 43% and 47%, respectively, compared to mean baseline testosterone concentrations. The mean testosterone C avg and C max in female subjects on day 7 increased by 60% and 58%, respectively, compared to mean baseline testosterone concentrations. Effect of showering In a randomized, 3-way (3 treatment periods without washout period) crossover study in 24 hypogonadal men, the effect of showering on testosterone exposure was assessed after once daily application of testosterone gel, 1.62% 81 mg to upper arms/shoulders for 7 days in each treatment period. On the 7th day of each treatment period, hypogonadal men took a shower with soap and water at either 2, 6, or 10 hours after drug application. The effect of showering at 2 or 6 hours post-dose on Day 7 resulted in 13% and 12% decreases in mean C avg , respectively, compared to Day 6 when no shower was taken after drug application. Showering at 10 hours after drug application had no effect on bioavailability. The amount of testosterone remaining in the outer layers of the skin at the application site on the 7th day was assessed using a tape stripping procedure and was reduced by at least 80% after showering 2-10 hours post-dose compared to on the 6th day when no shower was taken after drug application. Effect of hand washing In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated. Subjects used their hands to apply the maximum dose (81 mg testosterone) of testosterone gel, 1.62% to their upper arms and shoulders. Within 1 minute of applying the gel, subjects either washed or did not wash their hands prior to study personnel wiping the subjects’ hands with ethanol dampened gauze pads. The gauze pads were then analyzed for residual testosterone content. A mean (SD) of 0.1 (0.04) mg of residual testosterone (0.12% of the actual applied dose of testosterone, and a 96% reduction compared to when hands were not washed) was recovered after washing hands with water and soap. Effect of sunscreen or moisturizing lotion on absorption of testosterone In a randomized, 3-way (3 treatment periods without washout period) crossover study in 18 hypogonadal males, the effect of applying a moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the testosterone gel, 1.62% application site 1 hour after the application of testosterone gel, 1.62% 40.5 mg.

moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the testosterone gel, 1.62% application site 1 hour after the application of testosterone gel, 1.62% 40.5 mg. Application of moisturizing lotion increased mean testosterone C avg and C max by 14% and 17%, respectively, compared to testosterone gel, 1.62% administered alone. Application of sunscreen increased mean testosterone C avg and C max by 8% and 13%, respectively, compared to testosterone gel, 1.62% applied alone. Figure-2

14 CLINICAL STUDIES 14.1 Clinical Trials in Hypogonadal Males Testosterone gel, 1.62% was evaluated in a multi-center, randomized, double-blind, parallel-group, placebo-controlled study (182-day double-blind period) in 274 hypogonadal men with body mass index (BMI) 18-40 kg/m 2 and 18-80 years of age (mean age 53.8 years). The patients had an average serum testosterone concentration of <300 ng/dL, as determined by two morning samples collected on the same visit. Patients were Caucasian 83%, Black 13%, Asian or Native American 4%. 7.5% of patients were Hispanic. Patients were randomized to receive active treatment or placebo using a rotation method utilizing the abdomen and upper arms/shoulders for 182 days. All patients were started at a daily dose of 40.5 mg (two pump actuations) testosterone gel, 1.62% or matching placebo on Day 1 of the study. Patients returned to the clinic on Day 14, Day 28, and Day 42 for predose serum total testosterone assessments. The patient’s daily dose was titrated up or down in 20.25 mg increments if the predose serum testosterone value was outside the range of 350-750 ng/dL. The study included four active testosterone gel, 1.62% doses: 20.25 mg, 40.5 mg, 60.75 mg, and 81 mg daily. The primary endpoint was the percentage of patients with C avg within the normal range of 300-1000 ng/dL on Day 112. In patients treated with testosterone gel, 1.62%, 81.6% (146/179) had C avg within the normal range at Day 112. The secondary endpoint was the percentage of patients, with C max above three pre-determined limits. The percentages of patients with C max greater than 1500 ng/dL, and between 1800 and 2499 ng/dL on Day 112 were 11.2% and 5.5%, respectively. Two patients had a C max >2500 ng/dL on Day 112 (2510 ng/dL and 2550 ng/dL, respectively); neither of these 2 patients demonstrated an abnormal C max on prior or subsequent assessments at the same dose. Patients could agree to continue in an open-label, active treatment maintenance period of the study for an additional 182 days. Dose titrations on Days 14, 28, and 42 resulted in final doses of 20.25 mg – 81 mg on Day 112 as shown in Table 6. Table 6: Mean (SD) Testosterone Concentrations (C avg and C max ) by final dose on Days 112 and 364 Parameter Final Dose on Day 112 Placebo (n=27) 20.25 mg (n=12) 40.5 mg (n=34) 60.75 mg (n=54) 81 mg (n=79) All Active (n=179) C avg (ng/dL) 303 (135) 457 (275) 524 (228) 643 (285) 537 (240) 561 (259) C max (ng/dL) 450 (349) 663 (473) 798 (439) 958 (497) 813 (479) 845 (480) Final Dose on Day 364 20.25 mg (n=7) 40.5 mg (n=26) 60.75 mg (n=29) 81 mg (n=74) Continuing Active (n=136) C avg (ng/dL) 386 (130) 474 (176) 513 (222) 432 (186) 455 (192) C max (ng/dL) 562 (187) 715 (306) 839 (568) 649 (329) 697 (389) Figure 3 summarizes the pharmacokinetic profile of total testosterone in patients completing 112 days of testosterone gel, 1.62% treatment administered as a starting dose of 40.5 mg of testosterone (2 pump actuations) for the initial 14 days followed by possible titration according to the follow-up testosterone measurements. Figure 3: Mean (±SD) Steady-State Serum Total Testosterone Concentrations on Day 112 Efficacy was maintained in the group of men that received testosterone gel, 1.62% for one full year. In that group, 78% (106/136) had average serum testosterone concentrations in the normal range at Day 364. Figure 4 summarizes the mean total testosterone profile for these patients on Day 364.

Concentrations on Day 112 Efficacy was maintained in the group of men that received testosterone gel, 1.62% for one full year. In that group, 78% (106/136) had average serum testosterone concentrations in the normal range at Day 364. Figure 4 summarizes the mean total testosterone profile for these patients on Day 364. Figure 4: Mean (±SD) Steady-State Serum Total Testosterone Concentrations on Day 364 The mean estradiol and DHT concentration profiles paralleled the changes observed in testosterone. The levels of LH and FSH decreased with testosterone treatment. The decreases in levels of LH and FSH are consistent with reports published in the literature of long-term treatment with testosterone. figure-3 figure-4

<table width="100%"><col width="16%"/><col width="13%"/><col width="12%"/><col width="13%"/><col width="11%"/><col width="11%"/><col width="16%"/><tbody><tr><td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Parameter</content></paragraph></td><td align="center" colspan="6" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Final Dose on Day 112</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo</content></paragraph><paragraph><content styleCode="bold">(n=27)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">20.25 mg</content></paragraph><paragraph><content styleCode="bold">(n=12)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">40.5 mg</content></paragraph><paragraph><content styleCode="bold">(n=34)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">60.75 mg</content></paragraph><paragraph><content styleCode="bold">(n=54)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">81 mg</content></paragraph><paragraph><content styleCode="bold">(n=79)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Active</content></paragraph><paragraph><content styleCode="bold">(n=179)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">C_avg (ng/dL)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>303 (135)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>457 (275)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>524 (228)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>643 (285)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>537 (240)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>561 (259)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">C_max (ng/dL)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>450 (349)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>663 (473)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>798 (439)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>958 (497)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>813 (479)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>845 (480)</paragraph></td></tr><tr><td align="center" colspan="7" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Fi

ode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>813 (479)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>845 (480)</paragraph></td></tr><tr><td align="center" colspan="7" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Fi nal Dose on Day 364</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">20.25 mg</content></paragraph><paragraph><content styleCode="bold">(n=7)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">40.5 mg</content></paragraph><paragraph><content styleCode="bold">(n=26)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">60.75 mg</content></paragraph><paragraph><content styleCode="bold">(n=29)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">81 mg</content></paragraph><paragraph><content styleCode="bold">(n=74)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Continuing Active</content></paragraph><paragraph><content styleCode="bold">(n=136)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">C_avg (ng/dL)</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>386 (130)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>474 (176)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>513 (222)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>432 (186)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>455 (192)</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">C_max (ng/dL)</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"/><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>562 (187)</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>715 (306)</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>839 (568)</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>649 (329)</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>697 (389)</paragraph></td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Testosterone Gel, 1.62% is supplied in non-aerosol, metered-dose pumps that deliver 20.25 mg of testosterone per complete pump actuation. The pumps are composed of plastic and stainless steel and an LDPE/aluminum foil inner liner encased in rigid plastic with a polypropylene cap. Each 88 g metered-dose pump is capable of dispensing 75 g of gel or 60-metered pump actuations; each pump actuation dispenses 1.25 g of gel. Testosterone Gel, 1.62% is also supplied in unit-dose aluminum foil packets in cartons of 30. Each packet of 1.25 g or 2.5 g gel contains 20.25 mg or 40.5 mg testosterone, respectively. NDC Number Package Size 16714- 967 -01 88 g pump (each pump dispenses 60 metered pump actuations with each pump actuation containing 20.25 mg of testosterone in 1.25 g of gel) 16714- 968 -01 Each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel 16714- 968 -02 30 packets (each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel) 16714- 969 -01 Each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel 16714- 969 -02 30 packets (each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel) Store at controlled room temperature 20°C to 25°C (68°-77°F); excursions permitted to 15°C to 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Used Testosterone Gel, 1.62% pumps or used Testosterone Gel, 1.62% packets should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets.

<table width="100%"><col width="20%"/><col width="80%"/><tbody><tr styleCode="Toprule"><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">NDC Number</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Package Size</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule " valign="top"><paragraph>16714-<content styleCode="bold">967</content>-01</paragraph></td><td styleCode="Rrule Lrule Toprule " valign="top"><paragraph>88 g pump (each pump dispenses 60 metered pump actuations with each pump actuation containing 20.25 mg of testosterone in 1.25 g of gel)</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="top"><paragraph>16714-<content styleCode="bold">968</content>-01</paragraph></td><td styleCode="Rrule Lrule " valign="top"><paragraph>Each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="top"><paragraph>16714-<content styleCode="bold">968</content>-02 </paragraph></td><td styleCode="Rrule Lrule " valign="top"><paragraph>30 packets (each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel)</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="top"><paragraph>16714-<content styleCode="bold">969</content>-01</paragraph></td><td styleCode="Rrule Lrule " valign="top"><paragraph>Each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel</paragraph></td></tr><tr styleCode="Botrule"><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>16714-<content styleCode="bold">969</content>-02 </paragraph></td><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>30 packets (each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel)</paragraph></td></tr></tbody></table>

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Patients should be informed of the following: 17.1 Use in Men with Known or Suspected Prostate or Breast Cancer Men with known or suspected prostate or breast cancer should not use Testosterone Gel, 1.62% [see Contraindications (4) and Warnings and Precautions (5.1) ] . 17.2 Potential for Secondary Exposure to Testosterone and Steps to Prevent Secondary Exposure Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men [see Warnings and Precautions (5.2) ] . Cases of secondary exposure to testosterone have been reported in children. Physicians should advise patients of the reported signs and symptoms of secondary exposure, which may include the following: • In children: unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, and aggressive behavior. • In women: changes in hair distribution, increase in acne, or other signs of testosterone effects. • The possibility of secondary exposure to testosterone gel should be brought to the attention of a healthcare provider. • Testosterone Gel, 1.62% should be promptly discontinued until the cause of virilization is identified. Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from Testosterone Gel, 1.62% in men [see Medication Guide ] : • Children and women should avoid contact with unwashed or unclothed application site(s) of men using Testosterone Gel, 1.62%. • Patients using Testosterone Gel, 1.62% should apply the product as directed and strictly adhere to the following: • Wash hands with soap and water immediately after application. • Cover the application site(s) with clothing after the gel has dried. • Wash the application site(s) thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated. • In the event that unwashed or unclothed skin to which Testosterone Gel, 1.62% has been applied comes in contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible [see Dosage and Administration (2.2) , Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . 17.3 Potential for Venous Thromboembolism Inform patients that Testosterone Gel, 1.62% can cause venous thromboembolism. Advise patients of the signs and symptoms of venous thromboembolism, which may include the following: lower limb pain, edema, or erythema; and dyspnea or chest pain. Advise patients to promptly report the signs and symptoms of venous thromboembolism, discontinue use of Testosterone Gel, 1.62%, and seek urgent medical care. 17.4 Potential for Increase in Blood Pressure Inform patients that Testosterone Gel, 1.62% can increase BP which can increase cardiovascular risk over time. Instruct patients about the importance of monitoring BP periodically while on Testosterone Gel, 1.62%. If BP increases while on Testosterone Gel, 1.62%, antihypertensive medications may need to be started, added, or adjusted to control BP, or Testosterone Gel, 1.62% may need to be discontinued.

vascular risk over time. Instruct patients about the importance of monitoring BP periodically while on Testosterone Gel, 1.62%. If BP increases while on Testosterone Gel, 1.62%, antihypertensive medications may need to be started, added, or adjusted to control BP, or Testosterone Gel, 1.62% may need to be discontinued. 17.5 Potential Adverse Reactions with Androgens Patients should be informed that treatment with androgens may lead to adverse reactions which include: • Changes in urinary habits such as increased urination at night, trouble starting the urine stream, passing urine many times during the day, having an urge to go to the bathroom right away, having a urine accident, being unable to pass urine and weak urine flow. • Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness. • Too frequent or persistent erections of the penis. • Nausea, vomiting, changes in skin color, or ankle swelling. 17.6 Patients Should Be Advised of the Following Instructions for Use • Read the Medication Guide before starting Testosterone Gel, 1.62% therapy and to reread it each time the prescription is renewed. • Testosterone Gel, 1.62% should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women. • Keep Testosterone Gel, 1.62% out of the reach of children. • Testosterone Gel, 1.62% is an alcohol based product and is flammable; therefore avoid fire, flame or smoking until the gel has dried. • It is important to adhere to all recommended monitoring. • Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood. • Testosterone Gel, 1.62% is prescribed to meet the patient’s specific needs; therefore, the patient should never share Testosterone Gel, 1.62% with anyone. • Wait 2 hours before swimming or washing following application of Testosterone Gel, 1.62%. This will ensure that the greatest amount of Testosterone Gel, 1.62% is absorbed into their system. Medication Guides available at www.northstarrxllc.com/products or call 1-800-206-7821. Manufactured for: Northstar Rx LLC, Memphis, TN 38141 Manufactured by: Padagis ® , Yeruham, Israel Rev date: 08/2025 63200 N1 PH4

MEDICATION GUIDE Testosterone (tes-TOS-te-rone) Gel, 1.62% for topical use CIII What is the most important information I should know about Testosterone Gel, 1.62%? 1. Testosterone Gel, 1.62% can transfer from your body to others including, children and women. Children and women should avoid contact with the unwashed or not covered (unclothed) areas where Testosterone Gel, 1.62% has been applied to your skin. Early signs and symptoms of puberty have occurred in young children who have come in direct contact with testosterone by touching areas where men have used Testosterone Gel, 1.62%. Children Signs and symptoms of early puberty in a child when they come in direct contact with Testosterone Gel, 1.62% may include: Abnormal sexual changes: • enlarged penis or clitoris. • early growth of hair near the vagina or around the penis (pubic hair). • erections or acting out sexual urges (sex drive). Behavior problems: • acting aggressively, behaving in an angry or violent way. Women Signs and symptoms in women when they come in direct contact with Testosterone Gel, 1.62% may include: • changes in body hair. • an abnormal increase in pimples (acne). Stop using Testosterone Gel, 1.62% and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have happened through accidental touching of the area where you have applied Testosterone Gel, 1.62%. 2. To lower the risk of transfer of Testosterone Gel, 1.62% from your body to others, follow these important instructions: • Apply Testosterone Gel, 1.62% only to your shoulders and upper arms that will be covered by a short sleeve t-shirt. • Wash your hands right away with soap and water after applying Testosterone Gel, 1.62%. • After the gel has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered. • If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water. • If a child or woman touches the area where you have applied Testosterone Gel, 1.62%, that area on the child or woman should be washed well with soap and water right away. What is Testosterone Gel, 1.62%? Testosterone Gel, 1.62% is a prescription medicine that contains testosterone. Testosterone Gel, 1.62% is used to treat adult males who have low or no testosterone due to certain medical conditions. • Your healthcare provider will test your blood before you start and while you are using Testosterone Gel, 1.62%. • It is not known if Testosterone Gel, 1.62% is safe or effective to treat men who have low testosterone due to aging. • It is not known if Testosterone Gel, 1.62% is safe or effective in children younger than 18 years old. Improper use of Testosterone Gel, 1.62% may affect bone growth in children. Testosterone Gel, 1.62% is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your Testosterone Gel, 1.62% in a safe place to protect it. Never give your Testosterone Gel, 1.62% to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law. Testosterone Gel, 1.62% is not meant for use in women. Do not use Testosterone Gel, 1.62% if you: • have breast cancer. • have or might have prostate cancer. • are pregnant. Testosterone Gel, 1.62% may harm your unborn baby.

symptoms you have. Selling or giving away this medicine may harm others and is against the law. Testosterone Gel, 1.62% is not meant for use in women. Do not use Testosterone Gel, 1.62% if you: • have breast cancer. • have or might have prostate cancer. • are pregnant. Testosterone Gel, 1.62% may harm your unborn baby. • Women who are pregnant should avoid contact with the area of skin where Testosterone Gel, 1.62% has been applied. Before using Testosterone Gel, 1.62%, tell your healthcare provider about all of your medical conditions, including if you: • have breast cancer. • have or might have prostate cancer. • have urinary problems due to an enlarged prostate. • have heart problems. • have high blood pressure or are being treated for high blood pressure. • have kidney or liver problems. • have problems breathing while you sleep (sleep apnea). Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using Testosterone Gel, 1.62% with certain other medicines can affect each other. Especially, tell your healthcare provider if you take: • insulin • medicines that decrease blood clotting (blood thinners) • corticosteroids How should I use Testosterone Gel, 1.62%? • See the detailed Instructions for Use about how to use Testosterone Gel, 1.62% at the end of this Medication Guide. • It is important that you apply Testosterone Gel, 1.62% exactly as your healthcare provider tells you to. • Your healthcare provider may change your Testosterone Gel, 1.62% dose. Do not change your Testosterone Gel, 1.62% dose without talking to your healthcare provider. • Apply Testosterone Gel, 1.62% at the same time each morning. Testosterone Gel, 1.62% should be applied after showering or bathing. What are the possible side effects of Testosterone Gel, 1.62%? Testosterone Gel, 1.62% can cause serious side effects including: See “What is the most important information I should know about Testosterone Gel, 1.62%?” • If you already have enlargement of your prostate gland your signs and symptoms can get worse while using Testosterone Gel, 1.62%. This can include: o increased urination at night. o trouble starting your urine stream. o having to pass urine many times during the day. o having an urge to go to the bathroom right away. o having a urine accident. o being unable to pass urine or weak urine flow • Possible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use Testosterone Gel, 1.62%. • Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include leg pain, swelling, or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. • Increase in blood pressure. Testosterone Gel, 1.62% can increase your blood pressure. Increases in blood pressure can increase the risk of heart attack or stroke over time . If your blood pressure increases while on Testosterone Gel, 1.62%, blood pressure medicines may need to be started. If you are taking blood pressure medicines, new blood pressure medicines may need to be added or your current blood pressure medicines may need to be adjusted to control your blood pressure. If your blood pressure cannot be controlled, Testosterone Gel, 1.62% may need to be stopped. Your healthcare provider will monitor your blood pressure while you are being treated with Testosterone Gel, 1.62%. • In large doses Testosterone Gel, 1.62% may lower your sperm count. • Swelling of your ankles, feet, or body, with or without heart failure. • Enlarged or painful breasts. • Have problems breathing while you sleep (sleep apnea).

will monitor your blood pressure while you are being treated with Testosterone Gel, 1.62%. • In large doses Testosterone Gel, 1.62% may lower your sperm count. • Swelling of your ankles, feet, or body, with or without heart failure. • Enlarged or painful breasts. • Have problems breathing while you sleep (sleep apnea). Call your healthcare provider right away if you have any of the serious side effects listed above. The most common side effects of Testosterone Gel, 1.62% include: • increased prostate specific antigen (a test used to screen for prostate cancer) • mood swings • hypertension • increased red blood cell count • skin irritation where Testosterone Gel, 1.62% is applied Other side effects include more erections than are normal for you or erections that last a long time. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Testosterone Gel, 1.62%. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of Testosterone Gel, 1.62% Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Testosterone Gel, 1.62% for a condition for which it was not prescribed. Do not give Testosterone Gel, 1.62% to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Testosterone Gel, 1.62% that is written for health professionals. What are the ingredients in Testosterone Gel, 1.62%? Active ingredient: testosterone Inactive ingredients: carbopol 980, ethyl alcohol, isopropyl myristate, purified water and sodium hydroxide. For more information, call Northstar Rx LLC at 1-800-206-7821. This Medication Guide has been approved by the U.S. Food and Drug Administration Medication Guides available at www.northstarrxllc.com/products or call 1-800-206-7821. Rev. 08/2025

INSTRUCTIONS FOR USE Testosterone (tes-TOS-te-rone) Gel, 1.62% CIII for topical use Read this Instructions for Use for Testosterone Gel, 1.62% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment. Applying Testosterone Gel, 1.62%: • Testosterone Gel, 1.62% comes in a pump or in packets. • Before applying Testosterone Gel, 1.62% make sure that your shoulders and upper arms are clean, dry, and that there is no broken skin. • Testosterone Gel, 1.62% is to be applied to the area of your shoulders and upper arms that will be covered by a short sleeve t-shirt (See Figure A). Do not apply Testosterone Gel, 1.62% to any other parts of your body such as your stomach area (abdomen), penis, scrotum, chest, armpits (axillae), or knees. If you are using Testosterone Gel, 1.62% pump: • Before using a new bottle of Testosterone Gel, 1.62% for the first time, you will need to remove the cap and then prime the pump. To prime the Testosterone Gel, 1.62% pump, slowly push the pump all the way down 3 times, over the sink drain. Do not use any Testosterone Gel, 1.62% that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your Testosterone Gel, 1.62% pump is now ready to use. • Remove the cap from the pump. Then, put the spout opening at the top of the pump where the medicine comes out over the palm of your hand and slowly push the pump all the way down. Apply Testosterone Gel, 1.62% to the application site. You may also apply Testosterone Gel, 1.62% directly to the application site. Your healthcare provider will tell you the number of times to press the pump for each dose. • Wash your hands with soap and water right away. Find Your Dose as Prescribed by Your Healthcare Provider Application Method 1 pump 20.25 mg Apply 1 pump of Testosterone Gel, 1.62% to 1 upper arm and shoulder. 2 pumps 40.5 mg Apply 1 pump of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply 1 pump of Testosterone Gel, 1.62% to the opposite upper arm and shoulder. 3 pumps 60.75 mg Apply 2 pumps of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply 1 pump of Testosterone Gel, 1.62% to the opposite upper arm and shoulder. 4 pumps 81 mg Apply 2 pumps of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply 2 pumps of Testosterone Gel, 1.62% to the opposite upper arm and shoulder. If you are using Testosterone Gel, 1.62% packets: • Tear open the packet completely at the dotted line. Squeeze from the bottom of the packet to the top. • Squeeze all of the Testosterone Gel, 1.62% out of the packet into the palm of your hand. • Apply Testosterone Gel, 1.62% to the application site. You may also apply Testosterone Gel, 1.62% directly to the application site. • Let the application site dry completely before putting on a t-shirt. • Testosterone Gel, 1.62% is flammable until dry. Let Testosterone Gel, 1.62% dry before smoking or going near an open flame. • Avoid showering, swimming or bathing for at least 2 hours after you apply Testosterone Gel, 1.62%. • Wash your hands right away with soap and water after applying Testosterone Gel, 1.62%. Find Your Dose as Prescribed by Your Healthcare Provider Application Method One 20.25 mg packet 20.25 mg Apply 1 packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder.

least 2 hours after you apply Testosterone Gel, 1.62%. • Wash your hands right away with soap and water after applying Testosterone Gel, 1.62%. Find Your Dose as Prescribed by Your Healthcare Provider Application Method One 20.25 mg packet 20.25 mg Apply 1 packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder. One 40.5 mg packet 40.5 mg Apply half of the 40.5 mg packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply the remaining packet contents to the opposite upper arm and shoulder. One 40.5 mg packet and one 20.25 mg packet 60.75 mg Apply one 40.5 mg packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply one 20.25 mg packet of Testosterone Gel, 1.62% to the opposite upper arm and shoulder. Two 40.5 mg packets 81 mg Apply one 40.5 mg packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply one 40.5 mg packet of Testosterone Gel, 1.62% to the opposite upper arm and shoulder. How should I store Testosterone Gel, 1.62%? • Store Testosterone Gel, 1.62% at room temperature between 68°F to 77°F (20°C to 25°C). • When it is time to throw away the pump or packets, safely throw away used Testosterone Gel, 1.62% in the household trash. Be careful to prevent accidental exposure of children or pets. • Keep Testosterone Gel, 1.62% away from fire. Keep Testosterone Gel, 1.62% and all medicines out of the reach of children. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Medication Guides available at www.northstarrxllc.com/products or call 1-800-206-7821. Manufactured for: Northstar Rx LLC, Memphis, TN 38141 Manufactured by: Padagis ® , Yeruham, Israel Rev date: 08/2025 figure-a-instructions

<table width="100%"><col width="12%"/><col width="13%"/><col width="75%"/><tbody><tr><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Find Your Dose as Prescribed by Your Healthcare Provider</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Application Method</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>1 pump </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>20.25 mg</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Apply 1 pump of Testosterone Gel, 1.62% to 1 upper arm and shoulder.</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>2 pumps</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>40.5 mg</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Apply 1 pump of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply 1 pump of Testosterone Gel, 1.62% to the opposite upper arm and shoulder.</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>3 pumps</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>60.75 mg</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Apply 2 pumps of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply 1 pump of Testosterone Gel, 1.62% to the opposite upper arm and shoulder.</paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>4 pumps</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>81 mg</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Apply 2 pumps of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply 2 pumps of Testosterone Gel, 1.62% to the opposite upper arm and shoulder.</paragraph></td></tr></tbody></table>

oprule " valign="top"><paragraph>81 mg</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Apply 2 pumps of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply 2 pumps of Testosterone Gel, 1.62% to the opposite upper arm and shoulder.</paragraph></td></tr></tbody></table> <table width="100%"><col width="23%"/><col width="13%"/><col width="64%"/><tbody><tr><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Find Your Dose as Prescribed by Your Healthcare Provider</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Application Method</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>One 20.25 mg packet</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>20.25 mg</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Apply 1 packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder.</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>One 40.5 mg packet</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>40.5 mg</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Apply half of the 40.5 mg packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply the remaining packet contents to the opposite upper arm and shoulder.</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>One 40.5 mg packet and one 20.25 mg packet</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>60.75 mg</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Apply one 40.5 mg packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply one 20.25 mg packet of Testosterone Gel, 1.62% to the opposite upper arm and shoulder.</paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Two 40.5 mg packets</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>81 mg</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Apply one 40.5 mg packet of Testosterone Gel, 1.62% to 1 upper arm and shoulder and then apply one 40.5 mg packet of Testosterone Gel, 1.62% to the opposite upper arm and shoulder.</paragraph></td></tr></tbody></table>

WARNING: SECONDARY EXPOSURE TO TESTOSTERONE WARNING: SECONDARY EXPOSURE TO TESTOSTERONE See full prescribing information for complete boxed warning. Virilization has been reported in children who were secondarily exposed to topical testosterone products ( 5.2 ) Children should avoid contact with unwashed or unclothed application sites in men using testosterone topical solution ( 2.2 , 5.2 ) Healthcare providers should advise patients to strictly adhere to recommended instructions for use ( 2.2 , 5.2 , 17 ) Virilization has been reported in children who were secondarily exposed to topical testosterone products [see WARNINGS AND PRECAUTIONS ( 5.2 )] . Children should avoid contact with unwashed or unclothed application sites in men using testosterone topical solution [see DOSAGE AND ADMINISTRATION ( 2.2 ) and WARNINGS AND PRECAUTIONS ( 5.2 )] . Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see DOSAGE AND ADMINISTRATION ( 2.2 ), WARNINGS AND PRECAUTIONS ( 5.2 ) and PATIENT COUNSELING INFORMATION ( 17 )] . Warnings and Precautions ( 5.6 ) 03/2025

1 INDICATIONS AND USAGE Testosterone topical solution USP is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired) ( 1 ) Hypogonadotropic hypogonadism (congenital or acquired) ( 1 ) Limitations of use: Safety and efficacy of testosterone topical solution USP in men with "age-related hypogonadism" have not been established. ( 1 ) Safety and efficacy of testosterone topical solution USP in males <18 years old have not been established ( 8.4 ) Testosterone topical solution USP is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (FSH, LH) above the normal range. Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range. Limitations of use: Safety and efficacy of testosterone topical solution USP in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established. Safety and efficacy of testosterone topical solution USP in males <18 years old have not been established [see USE IN SPECIFIC POPULATIONS ( 8.4 )] .

2 DOSAGE AND ADMINISTRATION Prior to initiating testosterone topical solution USP, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. Prior to initiating testosterone topical solution USP, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range ( 2 ). Starting testosterone topical solution USP dose is 60 mg of testosterone (1 pump actuation of 30 mg of testosterone to each axilla), applied once daily, at the same time each morning. ( 2.1 ) Apply to clean, dry intact skin of the axilla, not to any other parts of the body including the abdomen or genitals ( 2.2 ) Dose adjustment: The dose of testosterone may be decreased from 60 mg (2 pump actuations) to 30 mg (1 pump actuation) or increased from 60 mg to 90 mg (3 pump actuations) or from 90 mg to 120 mg (4 pump actuations) based on the serum testosterone concentration from a single blood draw 2 to 8 hours after applying testosterone topical solution USP and at least 14 days after starting treatment or following dose adjustment. ( 2.2 ) Patients should wash hands immediately with soap and water after applying testosterone topical solution USP and cover the application site with clothing after the solution has dried. Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated. ( 2.2 ) The application site and dose of testosterone topical solution USP are not interchangeable with other topical testosterone products. ( 2.1 ) 2.1 Dosing and Dose Adjustment The recommended starting dose of testosterone topical solution USP is 60 mg of testosterone (2 pump actuations) applied once daily. To ensure proper dosing, serum testosterone concentrations should be measured after initiation of therapy to ensure that the desired concentrations (300 ng/dL to 1050 ng/dL) are achieved. The testosterone topical solution USP dose can be adjusted based on the serum testosterone concentration from a single blood draw 2 to 8 hours after applying testosterone topical solution USP and at least 14 days after starting treatment or following dose adjustment. If the measured serum testosterone concentration is below 300 ng/dL, the daily testosterone dose may be increased from 60 mg (2 pump actuations) to 90 mg (3 pump actuations) or from 90 mg to 120 mg (4 pump actuations). If the serum testosterone concentration exceeds 1050 ng/dL, the daily testosterone dose should be decreased from 60 mg (2 pump actuations) to 30 mg (1 pump actuation) as instructed by a physician. If the serum testosterone concentration consistently exceeds 1050 ng/dL at the lowest daily dose of 30 mg (1 pump actuation), testosterone topical solution USP therapy should be discontinued. The application site and dose of testosterone topical solution USP are not interchangeable with other topical testosterone products. 2.2 Administration Instructions Testosterone topical solution USP is applied to the axilla, preferably at the same time each morning, to clean, dry, intact skin. Do not apply testosterone topical solution USP to other parts of the body including to the scrotum, penis, abdomen, shoulders or upper arms.

sterone products. 2.2 Administration Instructions Testosterone topical solution USP is applied to the axilla, preferably at the same time each morning, to clean, dry, intact skin. Do not apply testosterone topical solution USP to other parts of the body including to the scrotum, penis, abdomen, shoulders or upper arms. After applying the solution, the application site should be allowed to dry completely prior to dressing. Avoid fire, flames or smoking until the solution has dried since alcohol based products, including testosterone topical solution USP, are flammable. When deodorants or antiperspirants are used as part of a regular program for personal hygiene, they should not interfere with the efficacy of testosterone topical solution USP in treating hypogonadism. If patients use an antiperspirant or deodorant (stick or roll-on) then it should be applied at least 2 minutes prior to the application of testosterone topical solution USP to avoid contamination of the stick or roll-on product. Patients should be advised to avoid swimming or washing the application site until two hours following application of testosterone topical solution USP [see CLINICAL PHARMACOLOGY ( 12.3 )] . To reduce the likelihood of interpersonal transfer of testosterone, the application site should always be washed prior to any skin-to-skin contact regardless of the length of time since application. [see WARNINGS AND PRECAUTIONS ( 5.2 )] . Testosterone topical solution USP is available as pump actuated metered-dose pump. Pump Actuated Metered-Dose Pump Testosterone topical solution USP is applied to the axilla using an applicator. When using testosterone topical solution USP for the first time, patients should be instructed to prime the pump by depressing the pump three times, discard any product dispensed directly into a basin, sink, or toilet and then wash the liquid away thoroughly. This priming should be done only prior to the first use of each pump. After priming, patients should completely depress the pump one time (1 pump actuation) to dispense 30 mg of testosterone. Ensure that the liquid is directed into the cup. The cup should be filled with no more than 30 mg (1 pump actuation) of testosterone. Dosing that requires greater than one pump actuation must be applied in increments of 30 mg as is shown in Table 1. Keeping the applicator upright, patients should place it up into the axilla and wipe steadily down and up into the axilla. If the solution drips or runs, it can be wiped back up with the applicator cup. The solution should not be rubbed into the skin with fingers or hand. The process is then repeated with application of 30 mg of testosterone (1 pump actuation) to the other axilla to achieve a total of 60 mg of testosterone applied. For patients prescribed the 90 mg dose of testosterone, the procedure is the same, but three applications are required. To dose 120 mg of testosterone, four applications are required alternating left and right for each application as shown in Table 1. When repeat application to the same axilla is required, the axilla should be allowed to dry completely before more testosterone topical solution USP is applied. After use, the applicator should be rinsed under room temperature, running water and then patted dry with a tissue. The applicator and cap are then replaced on the bottle for storage. Table 1: Application Technique Daily Prescribed Dose of Testosterone Number of Pump Actuations Application 30 mg (once daily) 1 Apply once to one axilla only (left OR right) 60 mg (once daily) 2 Apply once to the left axilla and then apply once to the right axilla. 90 mg (once daily) 3 Apply once to the left and once to the right axilla, wait for the product to dry, and then apply once again to the left OR right axilla.

ion 30 mg (once daily) 1 Apply once to one axilla only (left OR right) 60 mg (once daily) 2 Apply once to the left axilla and then apply once to the right axilla. 90 mg (once daily) 3 Apply once to the left and once to the right axilla, wait for the product to dry, and then apply once again to the left OR right axilla. 120 mg (once daily) 4 Apply once to the left and once to the right axilla, wait for the product to dry, and then apply once again to the left AND once to the right axilla. Hands should be washed thoroughly with soap and water after testosterone topical solution USP has been applied [see WARNINGS AND PRECAUTIONS ( 5.2 )] . Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from testosterone topical solution USP treated skin: Children and women should avoid contact with the unclothed or unwashed application sites on the skin of men using testosterone topical solution USP. Patients should wash their hands immediately with soap and water after application of testosterone topical solution USP. Patients should cover the application site(s) with clothing (e.g., a T-shirt) after the solution has dried. Prior to any situation in which direct skin-to-skin contact is anticipated, patients should wash the application site thoroughly with soap and water to remove any testosterone residue. In the event that unwashed or unclothed skin to which testosterone topical solution USP has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible. While interpersonal testosterone transfer can occur with a T-shirt on, it has been shown that transfer can be substantially reduced by wearing a T-shirt and the majority of residual testosterone is removed from the skin surface by washing with soap and water.

3 DOSAGE FORMS AND STRENGTHS Testosterone topical solution is available as follows: a metered-dose pump that delivers 30 mg of testosterone per pump. Each metered-dose pump is supplied with an applicator. ( 3 ) Testosterone topical solution is a topical solution available as a: metered-dose pump that delivers 30 mg of testosterone per pump. Each metered-dose pump is supplied with an applicator.

4 CONTRAINDICATIONS Men with carcinoma of the breast or known or suspected carcinoma of the prostate ( 4 , 5.1 ) Pregnant or breastfeeding women. Testosterone may cause fetal harm ( 4 , 8.1 , 8.3 ) Testosterone topical solution is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see WARNINGS AND PRECAUTION ( 5.1 )] . Testosterone topical solution is contraindicated in women who are, or who may become pregnant, or who are breastfeeding. Testosterone topical solution may cause fetal harm when administered to a pregnant woman. Testosterone topical solution may cause serious adverse reactions in nursing infants. If a pregnant woman is exposed to testosterone topical solution, she should be apprised of the potential hazard to the fetus. [see USE IN SPECIFIC POPULATIONS ( 8.1 , 8.3 )] .

5 WARNINGS AND PRECAUTIONS Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH ( 5.1 ) Avoid unintentional exposure of women or children to testosterone topical solution. Secondary exposure to testosterone can produce signs of virilization. Testosterone topical solution should be discontinued until the cause of the virilization is identified ( 2.2 , 5.2 ) Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Evaluate patients with signs or symptoms consistent with DVT or PE. ( 5.4 ) Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy. ( 5.5 ) Exogenous administration of testosterone may lead to azoospermia ( 5.9 ) Edema with or without congestive heart failure, may be a complication in patients with preexisting cardiac, renal, or hepatic disease ( 5.11 ). Sleep apnea may occur in those with risk factors ( 5.13 ) Monitor serum testosterone, prostate specific antigen (PSA), liver function, lipid concentrations, hematocrit and hemoglobin periodically ( 5.1 , 5.3 , 5.10 , 5.14 ) Testosterone topical solution is flammable until dry ( 5.17 ) 5.1 Worsening of Benign Prostatic Hyperplasia and Potential Risk of Prostate Cancer Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. Patients treated with Androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating treatment. It would be appropriate to reevaluate patients 3 to 6 months after initiation of treatment, and then in accordance with prostate cancer screening practices. [see CONTRAINDICATIONS ( 4 )] . 5.2 Potential for Secondary Exposure to Testosterone Cases of secondary exposure to testosterone in children and women have been reported with topical testosterone products applied to the abdomen or upper arms, including cases of secondary exposure resulting in virilization of children. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using testosterone topical solution [see DOSAGE AND ADMINISTRATION ( 2.2 ), USE IN SPECIFIC POPULATIONS ( 8.1 ) and CLINICAL PHARMACOLOGY ( 12.3 )] . Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone should also be brought to the attention of a physician. Testosterone therapy should be promptly discontinued at least until the cause of virilization has been identified. [see DOSAGE AND ADMINISTRATION ( 2.2 )] .

should be brought to the attention of a physician and the possibility of secondary exposure to testosterone should also be brought to the attention of a physician. Testosterone therapy should be promptly discontinued at least until the cause of virilization has been identified. [see DOSAGE AND ADMINISTRATION ( 2.2 )] . 5.3 Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating testosterone treatment. It would be appropriate to re-evaluate the hematocrit 3 to 6 months after starting testosterone treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. An increase in red blood cell mass may increase the risk of thromboembolic events. 5.4 Venous Thromboembolism There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone topical solution. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with testosterone topical solution and initiate appropriate workup and management [see ADVERSE REACTIONS ( 6.2 )] . 5.5 Cardiovascular Risk Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use testosterone topical solution. 5.6 Blood Pressure Increases Testosterone products can increase blood pressure. Blood pressure increases can increase cardiovascular (CV) risk over time. Monitor blood pressure periodically in men using testosterone products, especially men with hypertension. Testosterone products are not recommended for use in patients with uncontrolled hypertension. 5.7 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see DRUG ABUSE AND DEPENDENCE ( 9 )]. If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. 5.8 Use in Women Due to lack of controlled studies in women and potential virilizing effects, testosterone topical solution is not indicated for use in women [see CONTRAINDICATIONS ( 4 ) and USE IN SPECIFIC POPULATIONS ( 8.1 , 8.3 )] .

cted patients who present with serious cardiovascular or psychiatric adverse events. 5.8 Use in Women Due to lack of controlled studies in women and potential virilizing effects, testosterone topical solution is not indicated for use in women [see CONTRAINDICATIONS ( 4 ) and USE IN SPECIFIC POPULATIONS ( 8.1 , 8.3 )] . 5.9 Potential for Adverse Effects on Spermatogenesis At large doses of exogenous androgens, including testosterone topical solution, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count. 5.10 Hepatic Adverse Effects Prolonged use of high doses of orally active 17-alpha-alkyl androgens (methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatitis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatitis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. Testosterone topical solution is not known to cause these adverse effects. 5.11 Edema Androgens, including testosterone topical solution, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease [see ADVERSE REACTIONS ( 6 )] . 5.12 Gynecomastia Gynecomastia may develop and may persist in patients being treated with androgens, including testosterone topical solution, for hypogonadism. 5.13 Sleep Apnea The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity and chronic lung disease. 5.14 Lipids Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy. 5.15 Hypercalcemia Androgens, including testosterone topical solution, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. 5.16 Decreased Thyroxine-binding Globulin Androgens, including testosterone topical solution, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentration and increased resin uptake of T3 and T4. Free thyroid hormone concentration remain unchanged, however there is no clinical evidence of thyroid dysfunction. 5.17 Flammability Alcohol based products, including testosterone topical solution, are flammable; therefore, patients should be advised to avoid smoking, fire or flame until the testosterone topical solution dose applied has dried.

6 ADVERSE REACTIONS Most common adverse reactions (incidence >4%) are skin application site reactions, increased hematocrit, headache, diarrhea, vomiting, and increased serum PSA ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials in Hypogonadal Men Table 2 shows the treatment emergent adverse reactions that were reported by either >4% of 155 patients in a 120 day, Phase 3 study or by >4% of 71 patients who continued to use testosterone topical solution for up to 180 days. These data reflect the experience primarily with a testosterone dose of 60 mg, which was taken by all patients at the start of the study, and was the maintenance dose for 97 patients. However, the doses used varied from 30 mg to 120 mg. Event 120 Days (155 Patients) 180 Days (71 Patients) Application Site Irritation 11 (7%) 6 (8%) Application Site Erythema 8 (5%) 5 (7%) Headache 8 (5%) 4 (6%) Hematocrit Increased 6 (4%) 5 (7%) Diarrhea 4 (3%) 3 (4%) Vomiting 4 (3%) 3 (4%) PSA Increased 2 (1%) 3 (4%) Other less common adverse reactions reported by at least 2 patients in the 120 day trial included: application site edema, application site warmth, increased hemoglobin, hypertension, erythema (general), increased blood glucose, acne, nasopharyngitis, anger and anxiety. Other less common adverse reactions reported in fewer than 1% of patients in the 120 day trial included: asthenia, affect lability, folliculitis, increased lacrimation, breast tenderness, increased blood pressure, increased blood testosterone, neoplasm prostate and elevated red blood cell count. During the 120 day trial one patient discontinued treatment because of affect lability/anger which was considered possibly related to testosterone topical solution administration. During the 120 day clinical trial there was an increase in mean PSA values of 0.13 ± 0.68 ng/mL from baseline. At the end of the 180 day extension clinical trial, there was an overall increase in mean PSA values of 0.1 ± 0.54 ng/mL. Following the 120 day study, seventy-one (71) patients entered a two-month extension study with testosterone topical solution. Two patients (3%) had adverse reactions that led to discontinuation of treatment during the period from Day 120 to Day 180. These reactions were: one patient with application site irritation (considered possibly related to testosterone topical solution application) and one patient with dry skin and erythema, but not at the application site (considered not related to testosterone topical solution administration) and application site erythema (considered possibly related to testosterone topical solution administration). No serious adverse reactions to testosterone topical solution were reported during either the 120 day trial, or the extension to 180 days. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of testosterone topical solution.

sterone topical solution administration). No serious adverse reactions to testosterone topical solution were reported during either the 120 day trial, or the extension to 180 days. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of testosterone topical solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular Disorders myocardial infarction, stroke [see WARNINGS AND PRECAUTIONS ( 5.5 )] . Vascular Disorders Venous thromboembolism [see WARNINGS AND PRECAUTIONS ( 5.4 )] .

<table ID="ID232" width="95%"><col width="231"/><col width="227"/><col width="214"/><tbody><tr><td styleCode="Lrule Toprule Botrule Rrule" align="left"><content styleCode="bold"> Event</content> </td><td valign="top" styleCode="Lrule Toprule Botrule Rrule" align="center"><content styleCode="bold"> 120 Days </content> <content styleCode="bold"> (155 Patients) </content> </td><td valign="top" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> 180 Days </content> <content styleCode="bold"> (71 Patients) </content> </td></tr><tr><td styleCode=" Lrule Botrule" align="left"> Application Site Irritation </td><td styleCode="Lrule Botrule Rrule" align="center"> 11 (7%) </td><td styleCode=" Botrule Rrule" align="center"> 6 (8%) </td></tr><tr><td valign="top" styleCode=" Lrule Botrule" align="left"> Application Site Erythema </td><td styleCode="Lrule Botrule Rrule" align="center"> 8 (5%) </td><td styleCode=" Botrule Rrule" align="center"> 5 (7%) </td></tr><tr><td styleCode=" Lrule Botrule" align="left"> Headache </td><td styleCode="Lrule Botrule Rrule" align="center"> 8 (5%) </td><td styleCode=" Botrule Rrule" align="center"> 4 (6%) </td></tr><tr><td valign="top" styleCode=" Lrule Botrule" align="left"> Hematocrit Increased </td><td styleCode="Lrule Botrule Rrule" align="center"> 6 (4%) </td><td styleCode=" Botrule Rrule" align="center"> 5 (7%) </td></tr><tr><td valign="top" styleCode=" Lrule Botrule" align="left"> Diarrhea </td><td styleCode="Lrule Botrule Rrule" align="center"> 4 (3%) </td><td styleCode=" Botrule Rrule" align="center"> 3 (4%) </td></tr><tr><td styleCode=" Lrule Botrule" align="left"> Vomiting </td><td styleCode="Lrule Botrule Rrule" align="center"> 4 (3%) </td><td styleCode=" Botrule Rrule" align="center"> 3 (4%) </td></tr><tr><td valign="top" styleCode=" Lrule Botrule" align="left"> PSA Increased </td><td styleCode="Lrule Botrule Rrule" align="center"> 2 (1%) </td><td styleCode=" Botrule Rrule" align="center"> 3 (4%) </td></tr></tbody></table>

7 DRUG INTERACTIONS Androgens may decrease blood glucose and insulin requirement in diabetic patients ( 7.1 ). Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended ( 7.2 ). Use of testosterone with Adrenocorticotropic Hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease ( 7.3 ). 7.1 Insulin Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirement. 7.2 Oral anticoagulants Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of INR and prothrombin time is recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy. 7.3 Corticosteroids The concurrent use of testosterone with ACTH or corticosteroids may result in increased fluid retention and should be monitored cautiously, particularly in patients with cardiac, renal or hepatic disease.

8 USE IN SPECIFIC POPULATIONS There are insufficient long-term safety data in geriatric patients using testosterone topical solution to assess the potential risks of cardiovascular disease and prostate cancer ( 8.5 ). 8.1 Pregnancy Pregnancy Category X [see CONTRAINDICATIONS ( 4 )] Testosterone topical solution is contraindicated during pregnancy or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a female fetus to androgens may result in varying degrees of virilization. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. 8.3 Nursing Mothers Although it is not known how much testosterone transfers into human milk, testosterone topical solution is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants. Testosterone and other androgens may adversely affect lactation. [see CONTRAINDICATIONS ( 4 )] . 8.4 Pediatric Use Safety and efficacy of testosterone topical solution has not been established in males <18 years of age. Improper use may result in acceleration of bone age and premature closure of epiphyses. 8.5 Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone topical solution to determine whether efficacy in those over 65 years of age differs from younger patients. Of the 155 patients enrolled in the pivotal clinical study utilizing testosterone topical solution, 21 were over 65 years of age. Additionally, there were insufficient long-term safety data in these patients utilizing testosterone topical solution to assess a potential incremental risk of cardiovascular disease and prostate cancer. 8.6 Renal Impairment No formal studies were conducted involving patients with renal impairment. 8.7 Hepatic Impairment No formal studies were conducted involving patients with hepatic impairment. 8.8 Use in Men with Body Mass Index (BMI) >35 kg/m 2 Safety and efficacy of testosterone topical solution in males with BMI >35 kg/m 2 has not been established.

8.1 Pregnancy Pregnancy Category X [see CONTRAINDICATIONS ( 4 )] Testosterone topical solution is contraindicated during pregnancy or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a female fetus to androgens may result in varying degrees of virilization. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

8.3 Nursing Mothers Although it is not known how much testosterone transfers into human milk, testosterone topical solution is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants. Testosterone and other androgens may adversely affect lactation. [see CONTRAINDICATIONS ( 4 )] .

8.4 Pediatric Use Safety and efficacy of testosterone topical solution has not been established in males <18 years of age. Improper use may result in acceleration of bone age and premature closure of epiphyses.

8.5 Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone topical solution to determine whether efficacy in those over 65 years of age differs from younger patients. Of the 155 patients enrolled in the pivotal clinical study utilizing testosterone topical solution, 21 were over 65 years of age. Additionally, there were insufficient long-term safety data in these patients utilizing testosterone topical solution to assess a potential incremental risk of cardiovascular disease and prostate cancer.

9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance Testosterone topical solution contains testosterone, a Schedule III controlled substance in the Controlled Substances Act. 9.2 Abuse Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice. Abuse-Related Adverse Reactions Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression. The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility. The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty. Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 9.3 Dependence Behaviors Associated with Addiction Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors: Taking greater dosages than prescribed Continued drug use despite medical and social problems due to drug use Spending significant time to obtain the drug when supplies of the drug are interrupted Giving a higher priority to drug use than other obligations Having difficulty in discontinuing the drug despite desires and attempts to do so Experiencing withdrawal symptoms upon abrupt discontinuation of use Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

10 OVERDOSAGE No cases of overdose with testosterone topical solution have been reported in clinical trials. There is one report of acute overdosage by injection of testosterone enanthate: testosterone concentrations of up to 11,400 ng/dL were implicated in a cerebrovascular accident. Treatment of overdosage would consist of discontinuation of testosterone topical solution together with appropriate symptomatic and supportive care.

11 DESCRIPTION Testosterone topical solution USP is a clear, colorless, homogeneous solution containing 30 mg of testosterone USP in 1.5 mL of testosterone topical solution USP for topical administration through the axilla. The active pharmacologic ingredient in testosterone topical solution USP is testosterone USP. Testosterone USP is a white to practically white powder or crystals chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is: The inactive ingredients are ethanol, isopropyl alcohol, octisalate and povidone. structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). 12.2 Pharmacodynamics No specific pharmacodynamic studies were conducted using testosterone topical solution. 12.3 Pharmacokinetics Absorption Testosterone topical solution delivers physiologic circulating testosterone that approximate normal concentration range (i.e., 300 to 1050 ng/dL) seen in healthy men following application to the axilla. On the skin, the ethanol and isopropyl alcohol evaporate leaving testosterone and octisalate. The skin acts as a reservoir from which testosterone is released into the systemic circulation over time ( see Figure 1). In general, steady-state serum concentrations are achieved by approximately 14 days of daily dosing. Figure 1: Mean (±SD) Serum Testosterone Concentrations on Day 7 in Patients Following Testosterone Topical Solution Once-Daily Application of 30 mg, 60 mg, or 90 mg of Testosterone When testosterone topical solution treatment is discontinued after achieving steady-state, serum testosterone concentrations returned to their pretreatment concentrations by 7 to 10 days after the last application. Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and dihydrotestosterone (DHT). DHT concentration increased in parallel with testosterone concentration during testosterone topical solution treatment. The mean steady-state DHT/T ratio remained within normal limits and ranged from 0.17 to 0.26 across all doses on Days 15, 60, and 120. Excretion There is considerable variation in the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Potential for Testosterone Transfer: The potential for testosterone transfer from males dosed with testosterone topical solution to healthy females was evaluated in a clinical study conducted with a 2% testosterone formulation.

mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Potential for Testosterone Transfer: The potential for testosterone transfer from males dosed with testosterone topical solution to healthy females was evaluated in a clinical study conducted with a 2% testosterone formulation. 10 males were treated with 60 mg of testosterone in each axilla (the maximum testosterone dose of 120 mg). At 2 hours after the application of testosterone topical solution to the males, the females rubbed their outer forearms for 15 minutes on the axilla of the males. The males had covered the application area with a T-shirt. Serum concentrations of testosterone were monitored in the female subjects for 72 hours after the transfer procedure. Study results show a 13% and 17% increase in testosterone exposure (AUC [0 to 24] ) and maximum testosterone concentration (C max ), respectively, compared to baseline in these females. In a prior clinical study conducted with a 1% testosterone formulation under similar study conditions, direct skin-to-skin transfer showed a 131% and 297% increase in testosterone exposure (AUC [0 to 72] ) and maximum testosterone concentration (C max ), respectively, compared to when men had covered the application area with a T-shirt. In a clinical study conducted with a 2% testosterone formulation to evaluate the effect of washing on the residual amount of testosterone at the axilla, 10 healthy male subjects received 60 mg of testosterone to each axilla (the maximum testosterone dose of 120 mg). Following 5 minutes of drying time, the left axilla was wiped with alcohol towelettes which were assayed for testosterone content. Subjects were required to shower with soap and water 30 minutes after application. The right axilla was then wiped with alcohol towelettes which were assayed for testosterone content. A mean (SD) of 3.1 (2.8) mg of residual testosterone (i.e., 92.6% reduction compared to when axilla was not washed) was recovered after washing this area with soap and water. [see DOSAGE AND ADMINISTRATION ( 2.2 ) and WARNINGS AND PRECAUTIONS ( 5.2 )] . Use of Deodorants and Anti-perspirants: In a parallel designed clinical study evaluating the effect of deodorants and antiperspirants in healthy premenopausal females dosed with testosterone topical solution, each subject applied either a combined deodorant/antiperspirant spray (6 subjects) or stick (6 subjects) or a deodorant spray (6 subjects) to a single axilla 2 minutes before the application of 30 mg of testosterone to the same axilla. A control group of 6 subjects only applied 30 mg of testosterone to a single axilla. Blood samples were collected for 72 hours from all subjects following testosterone topical solution administration. Although a decrease of up to 33% of testosterone exposure (AUC [0 to 72] ) was observed when antiperspirants or deodorants are used 2 minutes prior to testosterone topical solution application, underarm deodorant or antiperspirant spray or stick products may be used 2 minutes prior to testosterone topical solution application as part of normal, consistent, and daily routine. [see DOSAGE AND ADMINISTRATION ( 2.2 ), and PATIENT COUNSELING INFORMATION ( 17.4 )] . Effect of Showering/Washing: In a parallel designed clinical study to evaluate the effect of washing on the testosterone systemic exposure, two groups of 6 healthy premenopausal female subjects were each dosed with 30 mg of testosterone to a single axilla. The application sites of each group were washed with soap and water 2 hours or 6 hours after the application of testosterone topical solution. A control group of 6 female subjects applied 30 mg of testosterone to a single axilla and did not wash the application site.

dosed with 30 mg of testosterone to a single axilla. The application sites of each group were washed with soap and water 2 hours or 6 hours after the application of testosterone topical solution. A control group of 6 female subjects applied 30 mg of testosterone to a single axilla and did not wash the application site. Blood samples were collected for 72 hours from all subjects following dosing with testosterone topical solution. A decrease of up to 35% of testosterone exposure (AUC [0 to 72] ) was observed when applications sites were washed 2 hours and 6 hours after testosterone topical solution application. Patients should be advised to avoid swimming or washing the application site until 2 hours following application of testosterone topical solution. [see DOSAGE AND ADMINISTRATION ( 2.2 ) and PATIENT COUNSELING INFORMATION ( 17.4 )] . figure 1

12.1 Mechanism of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

12.3 Pharmacokinetics Absorption Testosterone topical solution delivers physiologic circulating testosterone that approximate normal concentration range (i.e., 300 to 1050 ng/dL) seen in healthy men following application to the axilla. On the skin, the ethanol and isopropyl alcohol evaporate leaving testosterone and octisalate. The skin acts as a reservoir from which testosterone is released into the systemic circulation over time ( see Figure 1). In general, steady-state serum concentrations are achieved by approximately 14 days of daily dosing. Figure 1: Mean (±SD) Serum Testosterone Concentrations on Day 7 in Patients Following Testosterone Topical Solution Once-Daily Application of 30 mg, 60 mg, or 90 mg of Testosterone When testosterone topical solution treatment is discontinued after achieving steady-state, serum testosterone concentrations returned to their pretreatment concentrations by 7 to 10 days after the last application. Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and dihydrotestosterone (DHT). DHT concentration increased in parallel with testosterone concentration during testosterone topical solution treatment. The mean steady-state DHT/T ratio remained within normal limits and ranged from 0.17 to 0.26 across all doses on Days 15, 60, and 120. Excretion There is considerable variation in the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Potential for Testosterone Transfer: The potential for testosterone transfer from males dosed with testosterone topical solution to healthy females was evaluated in a clinical study conducted with a 2% testosterone formulation. 10 males were treated with 60 mg of testosterone in each axilla (the maximum testosterone dose of 120 mg). At 2 hours after the application of testosterone topical solution to the males, the females rubbed their outer forearms for 15 minutes on the axilla of the males. The males had covered the application area with a T-shirt. Serum concentrations of testosterone were monitored in the female subjects for 72 hours after the transfer procedure. Study results show a 13% and 17% increase in testosterone exposure (AUC [0 to 24] ) and maximum testosterone concentration (C max ), respectively, compared to baseline in these females. In a prior clinical study conducted with a 1% testosterone formulation under similar study conditions, direct skin-to-skin transfer showed a 131% and 297% increase in testosterone exposure (AUC [0 to 72] ) and maximum testosterone concentration (C max ), respectively, compared to when men had covered the application area with a T-shirt.

l study conducted with a 1% testosterone formulation under similar study conditions, direct skin-to-skin transfer showed a 131% and 297% increase in testosterone exposure (AUC [0 to 72] ) and maximum testosterone concentration (C max ), respectively, compared to when men had covered the application area with a T-shirt. In a clinical study conducted with a 2% testosterone formulation to evaluate the effect of washing on the residual amount of testosterone at the axilla, 10 healthy male subjects received 60 mg of testosterone to each axilla (the maximum testosterone dose of 120 mg). Following 5 minutes of drying time, the left axilla was wiped with alcohol towelettes which were assayed for testosterone content. Subjects were required to shower with soap and water 30 minutes after application. The right axilla was then wiped with alcohol towelettes which were assayed for testosterone content. A mean (SD) of 3.1 (2.8) mg of residual testosterone (i.e., 92.6% reduction compared to when axilla was not washed) was recovered after washing this area with soap and water. [see DOSAGE AND ADMINISTRATION ( 2.2 ) and WARNINGS AND PRECAUTIONS ( 5.2 )] . Use of Deodorants and Anti-perspirants: In a parallel designed clinical study evaluating the effect of deodorants and antiperspirants in healthy premenopausal females dosed with testosterone topical solution, each subject applied either a combined deodorant/antiperspirant spray (6 subjects) or stick (6 subjects) or a deodorant spray (6 subjects) to a single axilla 2 minutes before the application of 30 mg of testosterone to the same axilla. A control group of 6 subjects only applied 30 mg of testosterone to a single axilla. Blood samples were collected for 72 hours from all subjects following testosterone topical solution administration. Although a decrease of up to 33% of testosterone exposure (AUC [0 to 72] ) was observed when antiperspirants or deodorants are used 2 minutes prior to testosterone topical solution application, underarm deodorant or antiperspirant spray or stick products may be used 2 minutes prior to testosterone topical solution application as part of normal, consistent, and daily routine. [see DOSAGE AND ADMINISTRATION ( 2.2 ), and PATIENT COUNSELING INFORMATION ( 17.4 )] . Effect of Showering/Washing: In a parallel designed clinical study to evaluate the effect of washing on the testosterone systemic exposure, two groups of 6 healthy premenopausal female subjects were each dosed with 30 mg of testosterone to a single axilla. The application sites of each group were washed with soap and water 2 hours or 6 hours after the application of testosterone topical solution. A control group of 6 female subjects applied 30 mg of testosterone to a single axilla and did not wash the application site. Blood samples were collected for 72 hours from all subjects following dosing with testosterone topical solution. A decrease of up to 35% of testosterone exposure (AUC [0 to 72] ) was observed when applications sites were washed 2 hours and 6 hours after testosterone topical solution application. Patients should be advised to avoid swimming or washing the application site until 2 hours following application of testosterone topical solution. [see DOSAGE AND ADMINISTRATION ( 2.2 ) and PATIENT COUNSELING INFORMATION ( 17.4 )] .

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays. The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment.

14 CLINICAL STUDIES 14.1 Clinical Studies in Hypogonadal Men Testosterone topical solution was evaluated in a multicenter, open label, 120-day trial that enrolled 155 hypogonadal men at 26 clinical research centers. The median age of subjects was 53 years with a range of 19 to 78 years. Of the 144 subjects whose race was recorded, 122 (84.7%) were Caucasian, 13 (9.0%) were Hispanic, 6 (4.2%) were African Americans, 1 (0.7%) was Asian and 2 (1.4%) had race recorded as "Other". Patients were instructed to apply testosterone topical solution to unclothed, clean, dry, and unbroken skin. The solution was applied to the axillary area. Patients were not instructed to alter their normal grooming routine, e.g., shave under the arm. During the initial testosterone topical solution treatment period (Days 1 to 15) 143 patients were treated with 60 mg of testosterone daily. On Day 45 of the trial, patients were maintained at the same dose, or were titrated up or down, based on their 24 hour average serum testosterone concentration measured on Day 15. On Day 90 of the trial, patients were maintained at the same dose, or were titrated up or down, based on their 24 hour average serum testosterone concentration measured on Day 60. On day 120, 75% of responding patients finished the study on the starting dose of 60 mg of testosterone, while 2% had been titrated to 30 mg, 17% had been titrated to 90 mg and 6% had been titrated to the 120 mg dose. On day 60, 84.8% of subjects had total testosterone concentrations in the normal range. Of those who had sufficient data for analysis on day 120, 84.1%, had their average serum testosterone concentration in the normal range of 300 to 1050 ng/dL. Table 3 summarizes the proportion of subjects having average testosterone concentrations within the normal range on Days 60 and 120. Table 3: Proportion of subjects who had an average Serum Total Testosterone in the range 300 to 1050 ng/dL and completed 120 days of treatment (N=138 Three patients who withdrew from the study due to adverse reactions are included as treatment failures. ) Evaluation Time Statistics Value Baseline Testosterone Mean (SD) 194.6 ng/dL (92.9 ng/dL) Day 15 Normal Normal represents the percentage of patients with average testosterone concentration in the range of 300 to 1050 ng/dL. 76.1% On Day 15, 72.2% of the 90 subjects in the US study population had an average serum testosterone in the range of 300 ng/dL to 1050 ng/dL. 95% CI (69.0%, 83.2%) Day 60 Normal 84.8% 95% CI (78.8%, 90.8%) Day 120 Normal 84.1% 95% CI (77.9%, 90.2%) Of the 135 patients who completed the 120 day treatment, 123 patients did so with no deviation from the protocol. By day 120, average serum testosterone concentration was within normal range for 67% of those who titrated down on the 30 mg dose, 89% of those on the 60 mg dose, 86% of those who titrated up to 90 mg and 70% of those who titrated up to the 120 mg dose. Table 4 below summarizes the testosterone concentration data in the patients who completed 120 days.

rone concentration was within normal range for 67% of those who titrated down on the 30 mg dose, 89% of those on the 60 mg dose, 86% of those who titrated up to 90 mg and 70% of those who titrated up to the 120 mg dose. Table 4 below summarizes the testosterone concentration data in the patients who completed 120 days. Table 4: Baseline-unadjusted Arithmetic Mean (±SD) Steady-State Serum Testosterone Concentrations on Days 15, 60 and 120 in Patients Who Completed 120 Days of Treatment Dose of Testosterone Topical Solution 30 mg 60 mg 90 mg 120 mg Overall Day 15 [ N = 0 ] [ N = 135 ] [ N = 0 ] [ N = 0 ] [ N = 135 ] C a v g (ng/dL) -- 456 (±226) --- -- 456 (±226) C m a x (ng/dL) -- 744 (±502) -- -- 744 (±502) Day 60 [ N = 1 ] [ N = 105 ] [ N = 29 ] [ N = 0 ] [ N = 135 ] C a v g (ng/dL) 343 (--) 523 (±207) 368 (±138) -- 488 (±204) C m a x (ng/dL) 491 (--) 898 (±664) 646 (±382) -- 840 (±620) Day 120 [ N = 3 ] [ N = 97 ] [ N = 25 ] [ N = 10 ] [ N = 135 ] C a v g (ng/dL) 493 (±239) 506 (±175) 415 (±165) 390 (±160) 480 (±177) C m a x (ng/dL) 779 (±416) 839 (±436) 664 (±336) 658 (±353) 792 (±417) Figure 2 summarizes the pharmacokinetic profiles of total testosterone in patients completing 120 days of testosterone topical solution treatment administered as 60 mg of testosterone for the initial 15 days followed by possible titration according to follow-up testosterone measurements. Figure 2: Mean (± SD) Steady-State Serum Testosterone Concentrations on Day 120 (30, 60, 90 or 120 mg testosterone) in Patients Who Completed 120 Days (N=135) of Testosterone Topical Solution Once-Daily Treatment Figure 2

<table ID="ID295" width="100%"><caption>Table 3: Proportion of subjects who had an average Serum Total Testosterone in the range 300 to 1050 ng/dL and completed 120 days of treatment (N=138<footnote ID="ID295_1">Three patients who withdrew from the study due to adverse reactions are included as treatment failures.</footnote>)</caption><col width="24%"/><col width="35%"/><col width="41%"/><tbody><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Evaluation </content><content styleCode="bold">Time</content> </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Statistics </content> </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Value </content> </td></tr><tr><td align="left" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">Baseline Testosterone </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">Mean (SD) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">194.6 ng/dL (92.9 ng/dL) </td></tr><tr><td align="left" valign="middle" styleCode=" Lrule Rrule Toprule">Day 15 </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule">Normal<footnote ID="ID295_2">Normal represents the percentage of patients with average testosterone concentration in the range of 300 to 1050 ng/dL.</footnote> </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule">76.1%<footnote ID="ID295_3">On Day 15, 72.2% of the 90 subjects in the US study population had an average serum testosterone in the range of 300 ng/dL to 1050 ng/dL.</footnote> </td></tr><tr><td align="left" valign="middle" styleCode=" Lrule Rrule Botrule"> </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">95% CI </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">(69.0%, 83.2%) </td></tr><tr><td align="left" valign="middle" styleCode=" Lrule Rrule Toprule">Day 60 </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule">Normal<footnoteRef IDREF="ID295_2"/> </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">84.8% </td></tr><tr><td align="left" valign="middle" styleCode=" Lrule Rrule Botrule"> </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">95% CI </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">(78.8%, 90.8%) </td></tr><tr><td align="left" valign="middle" styleCode=" Lrule Rrule Toprule">Day 120 </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule">Normal<footnoteRef IDREF="ID295_2"/> </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">84.1% </td></tr><tr><td align="left" valign="middle" styleCode=" Lrule Rrule Botrule"> </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">95% CI </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">(77.9%, 90.2%) </td></tr></tbody></table>

Rrule Botrule Toprule">84.1% </td></tr><tr><td align="left" valign="middle" styleCode=" Lrule Rrule Botrule"> </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">95% CI </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">(77.9%, 90.2%) </td></tr></tbody></table> <table ID="ID297" width="102%"><caption>Table 4: Baseline-unadjusted Arithmetic Mean (&#xB1;SD) Steady-State Serum Testosterone Concentrations on Days 15, 60 and 120 in Patients Who Completed 120 Days of Treatment</caption><col width="16%"/><col width="16%"/><col width="17%"/><col width="18%"/><col width="17%"/><col width="18%"/><tbody><tr><td align="center" valign="top" colspan="1" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold"> </content></td><td align="center" valign="top" colspan="5" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Dose </content><content styleCode="bold">of </content><content styleCode="bold">Testosterone </content><content styleCode="bold">Topical </content><content styleCode="bold">Solution</content><content styleCode="bold"> </content></td></tr><tr><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">30 </content><content styleCode="bold">mg</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">60 </content><content styleCode="bold">mg</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">90 </content><content styleCode="bold">mg</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">120 </content><content styleCode="bold">mg</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Overall</content><content styleCode="bold"> </content></td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Day </content><content styleCode="bold">15</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">0</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">135</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">0</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">0</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">135</content><content st

ontent><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">135</content><content st yleCode="bold">]</content><content styleCode="bold"> </content></td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">C_a_v_g (ng/dL) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">-- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">456 (&#xB1;226) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">--- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">-- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">456 (&#xB1;226) </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">C_m_a_x (ng/dL) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">-- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">744 (&#xB1;502) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">-- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">-- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">744 (&#xB1;502) </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Day </content><content styleCode="bold">60 </content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">1</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">105</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">29</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">0</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">135</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">C_a_v_g (ng/dL) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">343 (--) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">523 (&#xB1;207) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">368 (&#xB1;138) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">-- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Topru

dle" styleCode=" Lrule Rrule Botrule Toprule">523 (&#xB1;207) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">368 (&#xB1;138) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">-- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Topru le">488 (&#xB1;204) </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">C_m_a_x (ng/dL) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">491 (--) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">898 (&#xB1;664) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">646 (&#xB1;382) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">-- </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">840 (&#xB1;620) </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Day </content><content styleCode="bold">120 </content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">3</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">97</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">25</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">10</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">[</content><content styleCode="bold">N</content><content styleCode="bold">=</content><content styleCode="bold">135</content><content styleCode="bold">]</content><content styleCode="bold"> </content></td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">C_a_v_g (ng/dL) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">493 (&#xB1;239) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">506 (&#xB1;175) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">415 (&#xB1;165) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">390 (&#xB1;160) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">480 (&#xB1;177) </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">C_m_a_x (ng/dL) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">779 (&#xB1;416) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">839 (&#xB1;436) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">664 (&#xB1;336) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">658 (&#xB1;353) </td><td align="center" valign="middle" st

n="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">839 (&#xB1;436) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">664 (&#xB1;336) </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">658 (&#xB1;353) </td><td align="center" valign="middle" st yleCode=" Lrule Rrule Botrule Toprule">792 (&#xB1;417) </td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Testosterone topical solution USP is available as a metered-dose pump containing 110 mL of solution. The pump is capable of dispensing 90 mL of solution in 60 metered pump actuations. One actuation delivers 30 mg of testosterone in 1.5 mL of solution. Each metered-dose pump is supplied with an applicator. The bottle and the applicator cup are not made with natural rubber latex. NDC Pump Type 68180-943-11 Pump Actuated 16.2 Storage and Handling Keep testosterone topical solution out of reach of children. Store upright at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Used testosterone topical solution bottles and applicators should be discarded in household trash in a manner that prevents accidental exposure of children or pets. 16.1 How Supplied Testosterone topical solution USP is available as a metered-dose pump containing 110 mL of solution. The pump is capable of dispensing 90 mL of solution in 60 metered pump actuations. One actuation delivers 30 mg of testosterone in 1.5 mL of solution. Each metered-dose pump is supplied with an applicator. The bottle and the applicator cup are not made with natural rubber latex. NDC Pump Type 68180-943-11 Pump Actuated

<table ID="ID378" width="100%"><col width="52%"/><col width="48%"/><tbody><tr><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">NDC</content><content styleCode="bold"> </content></td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Pump </content><content styleCode="bold">Type</content><content styleCode="bold"> </content></td></tr><tr><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">68180-943-11 </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">Pump Actuated </td></tr></tbody></table> <table ID="ID378" width="100%"><col width="52%"/><col width="48%"/><tbody><tr><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">NDC</content><content styleCode="bold"> </content></td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Pump </content><content styleCode="bold">Type</content><content styleCode="bold"> </content></td></tr><tr><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">68180-943-11 </td><td align="center" valign="middle" styleCode=" Lrule Rrule Botrule Toprule">Pump Actuated </td></tr></tbody></table>

16.2 Storage and Handling Keep testosterone topical solution out of reach of children. Store upright at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Used testosterone topical solution bottles and applicators should be discarded in household trash in a manner that prevents accidental exposure of children or pets.

17 PATIENT COUNSELING INFORMATION See FDA-Approved Medication Guide. Patients should be informed of the following information: 17.1 Use in Men with Known or Suspected Prostate or Breast Cancer Men with known or suspected prostate or breast cancer should not use testosterone topical solution [see CONTRAINDICATIONS ( 4 ) and WARNINGS AND PRECAUTION ( 5.1 )] . 17.2 Potential for Secondary Exposure to Testosterone and Steps to Prevent Secondary Exposure Cases of secondary exposure to testosterone in children and women have been reported with topical testosterone products applied to the abdomen, shoulders or upper arms, including cases of secondary exposure resulting in virilization of children, with signs and symptoms including enlargement of the penis or clitoris, premature development of pubic hair, increased erections, aggressive behavior and advanced bone age. Inappropriate changes in genital size or premature development of pubic hair or libido in children, or changes in hair distribution, increase in acne, or other signs of testosterone effects in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone topical solution also should be brought to the attention of a physician. Testosterone topical solution should be promptly discontinued at least until the cause of virilization is identified. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from testosterone topical solution treated skin: Testosterone topical solution should only be applied to the axilla, not to any other part of the body. Children and women should avoid contact with the unwashed skin of the axilla or unclothed application sites of men where testosterone topical solution has been applied. Patients should wash their hands immediately with soap and water after application of testosterone topical solution. Patients should cover the axilla application site(s) with clothing (e.g., a shirt) after waiting 3 minutes for the solution to dry. Prior to any situation in which direct skin-to-skin contact of the axilla is anticipated, patients should wash the axilla to which testosterone topical solution has been applied thoroughly with soap and water to remove any testosterone residue. In the event that unwashed or unclothed skin to which testosterone topical solution has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible [see DOSAGE AND ADMINISTRATION ( 2.2 ), WARNINGS AND PRECAUTIONS ( 5.2 ) and CLINICAL PHARMACOLOGY ( 12.3 )] . 17.3 Potential Adverse Reactions with Androgens Patients should be informed that treatment with Androgens may lead to adverse reactions which include: Changes in urinary habits such as increased urination at night, trouble starting your urine stream, passing urine many times during the day, having an urge that you have to go to the bathroom right away, having urine accident, being unable to pass urine and having a weak urine flow. Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness. Too frequent or persistent erections of the penis. Nausea, vomiting, changes in skin color, or ankle swelling. 17.4 Patients should be advised of these Application Instructions Ensure that the patient understands how to administer the correct dose.

including those associated with sleep, or excessive daytime sleepiness. Too frequent or persistent erections of the penis. Nausea, vomiting, changes in skin color, or ankle swelling. 17.4 Patients should be advised of these Application Instructions Ensure that the patient understands how to administer the correct dose. The pump should be primed by depressing it 3 times prior to its first use. No priming is needed with subsequent uses of that pump. Testosterone topical solution should NOT be applied to the scrotum, penis, abdomen, shoulders or upper arms. With testosterone doses greater than 60 mg, which require two applications of testosterone topical solution to the same axilla, the product should be allowed to dry after the first application before the second is applied. Testosterone topical solution should be applied once daily at approximately the same time each day. Testosterone topical solution should be applied to clean, dry skin. Patients may use an antiperspirant or deodorant spray before applying testosterone topical solution. If patients use a stick or roll-on antiperspirant or deodorant, then it should be applied at least 2 minutes prior to application of testosterone topical solution to avoid contamination of the stick or roll-on product. Avoid swimming or washing the application site until two hours following application of testosterone topical solution [see DOSAGE AND ADMINISTRATION ( 2 ) and CLINICAL PHARMACOLOGY ( 12.3 )] . Avoid splashing in the eyes. In case of contact with eyes, flush thoroughly with water. If irritation persists, seek medical advice. Do not drink testosterone topical solution. LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc. Manufactured for: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States Manufactured by: Lupin Limited Pithampur (M.P.) – 454 775 India March 2025 ID#:280120 Image

MEDICATION GUIDE Testosterone (tes TOS ter one) Topical Solution USP, for topical use CIII What is the most important information I should know about testosterone topical solution? 1. Testosterone topical solution can transfer from your body to others including, children and women. Children and women should avoid contact with the unwashed or not covered (unclothed) areas where testosterone topical solution has been applied to your skin. Early signs and symptoms of puberty have occurred in young children who have come in direct contact with testosterone by touching areas where men have used testosterone topical solution. Children Signs and symptoms of early puberty in a child when they come in direct contact with testosterone topical solution may include: Abnormal sexual changes: enlarged penis or clitoris. early growth of hair near the vagina or around the penis (pubic hair). erections or acting out sexual urges (sex drive). Behavior problems : acting aggressively, behaving in an angry or violent way. Women Signs and symptoms in women when they come in direct contact with testosterone topical solution may include: changes in body hair. an abnormal increase in pimples (acne). Stop using testosterone topical solution and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have happened through accidental touching of the area where you have applied testosterone topical solution: 2. To lower the risk of transfer of testosterone topical solution from your body to others, follow these important instructions: Apply testosterone topical solution only to your armpits. Wash your hands right away with soap and water after applying testosterone topical solution. After the solution has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered. If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water. If a child or woman touches the area where you have applied testosterone topical solution, that area on the child or woman should be washed well with soap and water right away. What is testosterone topical solution? Testosterone topical solution is a prescription medicine that contains testosterone. Testosterone topical solution is used to treat adult males who have low or no testosterone due to certain medical conditions. Your healthcare provider will test your blood before you start and while you are using testosterone topical solution. It is not known if testosterone topical solution is safe or effective to treat men who have low testosterone due to aging. It is not known if testosterone topical solution is safe and effective in children younger than 18 years old. Improper use of testosterone topical solution may affect bone growth in children. Testosterone topical solution is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your testosterone topical solution in a safe place to protect it. Never give testosterone topical solution to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and it is against the law. Testosterone topical solution is not meant for use in women. Do not use testosterone topical solution if you: have breast cancer. have or might have prostate cancer.

cal solution to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and it is against the law. Testosterone topical solution is not meant for use in women. Do not use testosterone topical solution if you: have breast cancer. have or might have prostate cancer. are pregnant or may become pregnant or are breastfeeding. Testosterone topical solution may harm your unborn or breastfeeding baby. Women who are pregnant or who may become pregnant should avoid contact with the area of the skin where testosterone topical solution has been applied. Before using testosterone topical solution, tell your healthcare provider about all of your medical conditions, including if you: have breast cancer. have or might have prostate cancer. have urinary problems due to an enlarged prostate. have high blood pressure or are being treated for high blood pressure. have heart problems. have kidney or liver problems. have problems breathing while you sleep (sleep apnea). Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using testosterone topical solution with other medicines can affect each other. Especially tell your healthcare provider if you take: insulin medicines that decrease blood clotting (blood thinners) corticosteroids How should I use testosterone topical solution? See the detailed Instructions for Use for information about how to use testosterone topical solution at the end of this Medication Guide. Testosterone topical solution comes in a metered-dose pump or twist actuated dispenser. Make sure you have the right pump or dispenser that is prescribed for you. It is important that you apply testosterone topical solution exactly as your healthcare provider tells you to. Your healthcare provider may change your testosterone topical solution dose. Do not change your testosterone topical solution dose without talking to your healthcare provider. Apply testosterone topical solution at about the same time each morning. Testosterone topical solution should be applied after showering or bathing. What are the possible side effects of testosterone topical solution? Testosterone topical solution can cause serious side effects including: See also "What is the most important information I should know about testosterone topical solution?" If you already have an enlarged prostate, your symptoms can get worse while using testosterone topical solution. This can include: increased urination at night. trouble starting your urine stream. having to pass urine many times during the day. having an urge to go to the bathroom right away. having a urine accident. being unable to pass urine or weak urine flow. Possible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use testosterone topical solution. Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. Possible increased risk of heart attack or stroke. In large doses testosterone topical solution may lower your sperm count. Swelling of your ankles, feet, or body, with or without heart failure . Enlarged or painful breasts. Have problems breathing while you sleep (sleep apnea). Call your healthcare provider right away if you have any of the serious side effects listed above.

e doses testosterone topical solution may lower your sperm count. Swelling of your ankles, feet, or body, with or without heart failure . Enlarged or painful breasts. Have problems breathing while you sleep (sleep apnea). Call your healthcare provider right away if you have any of the serious side effects listed above. The most common side effects of testosterone topical solution include: skin redness or irritation where testosterone topical solution is applied increased red blood cell count headache diarrhea vomiting increase in blood level of Prostate Specific Antigen (a test used to screen for prostate cancer) Other side effects include more erections than are normal for you or erections that last a long time. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of testosterone topical solution. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of testosterone topical solution. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use testosterone topical solution for a condition for which it was not prescribed. Do not give testosterone topical solution to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about testosterone topical solution that is written for health professionals. What are the ingredients in testosterone topical solution? Active ingredient: testosterone USP. Inactive ingredients: ethanol, isopropyl alcohol, octisalate, and povidone. The bottle and the applicator cup are not made with natural rubber latex. For more information, go to www.lupinpharmaceuticals.com or call 1-800-399-2561. This Medication Guide has been approved by the U.S. Food and Drug Administration. INSTRUCTIONS FOR USE Testosterone (tes TOS ter one) Topical Solution USP, for topical use, CIII Read this Instructions for Use for testosterone topical solution before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment. Applying Testosterone Topical Solution: Testosterone topical solution is to be applied to the armpits only. Do not apply mtestosterone topical solution to any other parts of your body such as your stomach area (abdomen), penis, scrotum, shoulders or upper arms. Do not apply testosterone topical solution with your fingers or hands. Apply testosterone topical solution at about the same time each morning. Testosterone topical solution should be applied after showering or bathing. Avoid swimming or bathing for at least 2 hours after you apply testosterone topical solution. You can use an antiperspirant or deodorant before applying testosterone topical solution. If you use antiperspirant or deodorant, then it should be applied at least 2 minutes before you apply testosterone topical solution. Testosterone topical solution is flammable until dry. Let testosterone topical solution dry before smoking or going near an open flame. Avoid splashing in the eyes. In case of contact with eyes, flush thoroughly with water. If irritation persists, seek medical advice. Testosterone Topical Solution Figure 1 Before using a new bottle of testosterone topical solution for the first time, you will need to prime the pump. To prime the testosterone topical solution pump gently push down on the pump 3 times. Do not use any testosterone topical solution that came out while priming.

l advice. Testosterone Topical Solution Figure 1 Before using a new bottle of testosterone topical solution for the first time, you will need to prime the pump. To prime the testosterone topical solution pump gently push down on the pump 3 times. Do not use any testosterone topical solution that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your testosterone topical solution pump is now ready to use. Use testosterone topical solution exactly as your healthcare provider tells you to use it. Your healthcare provider will tell you the dose of testosterone topical solution that is right for you. Apply your dose correctly by following the application instructions in the table below. Find Your Dose as Prescribed by Your Healthcare Provider Each application equals 1 press (depression) of the pump. 30 mg Apply 1 application one time to one armpit only (left or right). 60 mg Apply 2 applications: one to the left armpit and then one to the right armpit. 90 mg Apply 3 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left or right armpit. 120 mg Apply 4 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left and one to the right armpit. Before applying testosterone topical solution, make sure that your armpit is clean, dry and that there is no broken skin. Figure 2 Remove the cap and the applicator cup from the pump. Then, position the nozzle over the applicator cup and gently press down on (depress) the pump ( see Figure 2 ). Figure 3 To apply the testosterone topical solution, keep the applicator upright, place it up into the armpit application site and wipe steadily down and up ( see Figure 3 ). If testosterone topical solution drips or runs, wipe it back up with the applicator cup. Do not rub in the solution with your fingers or hand after it has been applied. Let the application site dry completely for 3 minutes before putting on a shirt. After you have finished applying testosterone topical solution, rinse the applicator cup with room temperature running water, and then pat it dry with a tissue. Carefully replace the applicator cup and cap back onto the bottle and make sure you store the bottle safely. Clean up any spilled solution from surfaces such as the sink or floor to make sure others do not come into contact with it. Wash your hands with soap and water right away. How should I store testosterone topical solution? Store testosterone topical solution upright at room temperature between 68°F to 77°F (20°C to 25°C). When it is time to throw away the bottle, safely throw away all parts of the testosterone topical solution dispenser including the bottle applicator cup and cap into the household trash. Be careful to prevent accidental exposure of children or pets. Keep testosterone topical solution away from fire. Keep testosterone topical solution and all medicines out of the reach of children. This Instructions for Use has been approved by the U.S. Food and Drug Administration. LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc. Manufactured for: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States Manufactured by: Lupin Limited Pithampur (M.P.) – 454 775 India March 2024 ID#: 280140 Figure 1 Figure 2 Figure 3 Image

<table ID="ID338" width="99%" styleCode="Noautorules"><col width="187"/><col width="517"/><tbody><tr><td styleCode="Lrule Toprule Botrule Rrule" align="left"><content styleCode="bold"> Find Your Dose as Prescribed by Your Healthcare Provider</content> </td><td valign="bottom" styleCode=" Toprule Botrule Rrule" align="center"><content styleCode="bold"> Each application equals 1 press (depression) of the pump.</content> </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> 30 mg </td><td valign="top" styleCode=" Botrule Rrule" align="left"> Apply 1 application one time to one armpit only (left <content styleCode="bold"> or </content> right). </td></tr><tr><td valign="top" styleCode="Lrule Botrule Rrule" align="left"> 60 mg </td><td valign="top" styleCode=" Botrule Rrule" align="left"> Apply 2 applications: one to the left armpit and then one to the right armpit. </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"> 90 mg </td><td styleCode=" Botrule Rrule" align="left"> Apply 3 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left <content styleCode="bold"> or </content> right armpit. </td></tr><tr><td styleCode="Lrule Botrule Rrule" align="left"> 120 mg </td><td valign="top" styleCode=" Botrule Rrule" align="left"> Apply 4 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left <content styleCode="bold"> and </content> one to the right armpit. </td></tr></tbody></table>