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1 INDICATIONS AND USAGE Finasteride tablets are indicated for the treatment of male pattern hair loss (androgenetic alopecia) in MEN ONLY . Efficacy in bitemporal recession has not been established. Finasteride tablets are not indicated for use in women. • Finasteride is a 5α-reductase inhibitor indicated for the treatment of male pattern hair loss (androgenetic alopecia) in MEN ONLY (1) . • Finasteride tablets are not indicated for use in women ( 1 , 4 , 5.1 ).

2 DOSAGE AND ADMINISTRATION Finasteride tablets may be administered with or without meals. The recommended dose of finasteride is one tablet (1 mg) taken once daily. In general, daily use for three months or more is necessary before benefit is observed. Continued use is recommended to sustain benefit, which should be re-evaluated periodically. Withdrawal of treatment leads to reversal of effect within 12 months. • Finasteride tablets may be administered with or without meals (2) . • One tablet (1 mg) taken once daily (2) . • In general, daily use for three months or more is necessary before benefit is observed (2) .

4 CONTRAINDICATIONS Finasteride tablets are contraindicated in the following: • Pregnancy. Finasteride use is contraindicated in women when they are or may potentially be pregnant. Because of the ability of Type II 5α-reductase inhibitors to inhibit the conversion of testosterone to 5α-dihydrotestosterone (DHT), finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant woman who receives finasteride. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant woman should be apprised of the potential hazard to the male fetus. [See Warnings and Precautions (5.1) , Use in Specific Populations (8.1) , How Supplied/Storage and Handling (16) and Patient Counseling Information (17) .] In female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring. • Hypersensitivity to any component of this medication. • Pregnancy (4, 5.1, 8.1, 16) . • Hypersensitivity to any components of this product (4) .

5 WARNINGS AND PRECAUTIONS • Finasteride is not indicated for use in women or pediatric patients (5.1, 5.4) . • Women should not handle crushed or broken finasteride tablets when they are pregnant or may potentially be pregnant due to potential risk to a male fetus (5.1, 8.1, 16) . • Finasteride causes a decrease in serum PSA levels. Any confirmed increase in PSA while on finasteride may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for men not taking a 5α-reductase inhibitor (5.2) . • 5α-reductase inhibitors may increase the risk of high-grade prostate cancer (5.3, 6.1) . 5.1 Exposure of Women — Risk to Male Fetus Finasteride is not indicated for use in women. Women should not handle crushed or broken finasteride tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Finasteride tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed. [See Indications and Usage (1) , Contraindications (4) , Use in Specific Populations (8.1) , How Supplied/Storage and Handling (16) and Patient Counseling Information (17) .] 5.2 Effects on Prostate Specific Antigen (PSA) In clinical studies with finasteride, 1 mg in men 18 to 41 years of age, the mean value of serum prostate specific antigen (PSA) decreased from 0.7 ng/mL at baseline to 0.5 ng/mL at Month 12. Further, in clinical studies with finasteride, 5 mg when used in older men who have benign prostatic hyperplasia (BPH), PSA levels are decreased by approximately 50%. Other studies with finasteride 5 mg showed it may also cause decreases in serum PSA in the presence of prostate cancer. These findings should be taken into account for proper interpretation of serum PSA when evaluating men treated with finasteride. Any confirmed increase from the lowest PSA value while on finasteride may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5α-reductase inhibitor. Non-compliance to therapy with finasteride may also affect PSA test results. 5.3 Increased Risk of High-Grade Prostate Cancer with 5α-Reductase Inhibitors Men aged 55 and over with a normal digital rectal examination and PSA ≤3 ng/mL at baseline taking finasteride 5 mg/day (5 times the dose of finasteride) in the 7-year Prostate Cancer Prevention Trial (PCPT) had an increased risk of Gleason score 8 to 10 prostate cancer (finasteride 1.8% vs. placebo 1.1%). [See Adverse Reactions (6.1) .] Similar results were observed in a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART) (1% dutasteride vs. 0.5% placebo). 5α-reductase inhibitors may increase the risk of development of high-grade prostate cancer. Whether the effect of 5α-reductase inhibitors to reduce prostate volume, or study-related factors, impacted the results of these studies has not been established. 5.4 Pediatric Patients Finasteride is not indicated for use in pediatric patients [see Use in Specific Populations (8.4) ] .

6 ADVERSE REACTIONS The most common adverse reactions, reported in ≥1% of patients treated with finasteride and greater than in patients treated with placebo are: decreased libido, erectile dysfunction and ejaculation disorder (6.1) .To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 clinical practice. Clinical Studies for Finasteride 1 mg in the Treatment of Male Pattern Hair Loss In three controlled clinical trials for finasteride of 12-month duration, 1.4% of patients taking finasteride (n=945) were discontinued due to adverse experiences that were considered to be possibly, probably or definitely drug-related (1.6% for placebo; n=934). Clinical adverse experiences that were reported as possibly, probably or definitely drug-related in ≥1% of patients treated with finasteride or placebo are presented in Table 1. TABLE 1: Drug-Related Adverse Experiences for Finasteride 1 mg in Year 1 (%) MALE PATTERN HAIR LOSS Finasteride N=945 Placebo N=934 Decreased Libido 1.8 1.3 Erectile Dysfunction 1.3 0.7 Ejaculation Disorder (Decreased Volume of Ejaculate) 1.2 (0.8) 0.7 (0.4) Discontinuation due to drug-related sexual adverse experiences 1.2 0.9 Integrated analysis of clinical adverse experiences showed that during treatment with finasteride, 36 (3.8%) of 945 men had reported one or more of these adverse experiences as compared to 20 (2.1%) of 934 men treated with placebo (p=0.04). Resolution occurred in men who discontinued therapy with finasteride due to these side effects and in most of those who continued therapy. The incidence of each of the above adverse experiences decreased to ≤0.3% by the fifth year of treatment with finasteride. In a study of finasteride 1 mg daily in healthy men, a median decrease in ejaculate volume of 0.3 mL (-11%) compared with 0.2 mL (-8%) for placebo was observed after 48 weeks of treatment. Two other studies showed that finasteride at 5 times the dosage of finasteride (5 mg daily) produced significant median decreases of approximately 0.5 mL (-25%) compared to placebo in ejaculate volume, but this was reversible after discontinuation of treatment. In the clinical studies with finasteride, the incidences for breast tenderness and enlargement, hypersensitivity reactions, and testicular pain in finasteride-treated patients were not different from those in patients treated with placebo . Controlled Clinical Trials and Long-Term Open Extension Studies for Finasteride 5 mg and AVODART (dutasteride) in the Treatment of Benign Prostatic Hyperplasia In the finasteride 5 mg long-term efficacy and safety study, a 4-year controlled clinical study, 3040 patients between the ages of 45 and 78 with symptomatic BPH and an enlarged prostate were evaluated for safety over a period of 4 years (1524 on finasteride 5 mg/day and 1516 on placebo). 3.7% (57 patients) treated with finasteride 5 mg and 2.1% (32 patients) treated with placebo discontinued therapy as a result of adverse reactions related to sexual function, which are the most frequently reported adverse reactions.

for safety over a period of 4 years (1524 on finasteride 5 mg/day and 1516 on placebo). 3.7% (57 patients) treated with finasteride 5 mg and 2.1% (32 patients) treated with placebo discontinued therapy as a result of adverse reactions related to sexual function, which are the most frequently reported adverse reactions. Table 2 presents the only clinical adverse reactions considered possibly, probably or definitely drug related by the investigator, for which the incidence on finasteride 5 mg was ≥1% and greater than placebo over the 4 years of the study. In years 2 to 4 of the study, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder. TABLE 2: Drug-Related Adverse Experiences for Finasteride 5 mg BENIGN PROSTATIC HYPERPLASIA *Combined Years 2 to 4 N = 1524 and 1516, finasteride vs. placebo, respectively Year 1 (%) Years 2, 3 and 4* (%) Finasteride 5 mg Placebo Finasteride 5 mg Placebo Impotence 8.1 3.7 5.1 5.1 Decreased Libido 6.4 3.4 2.6 2.6 Decreased Volume of Ejaculate 3.7 0.8 1.5 0.5 Ejaculation Disorder 0.8 0.1 0.2 0.1 Breast Enlargement 0.5 0.1 1.8 1.1 Breast Tenderness 0.4 0.1 0.7 0.3 Rash 0.5 0.2 0.5 0.1 The adverse experience profiles in the 1-year, placebo-controlled, Phase III BPH studies and the 5-year open extensions with finasteride 5 mg and long-term efficacy and safety study were similar. There is no evidence of increased sexual adverse experiences with increased duration of treatment with finasteride 5 mg. New reports of drug-related sexual adverse experiences decreased with duration of therapy. During the 4- to 6-year placebo- and comparator-controlled Medical Therapy of Prostatic Symptoms (MTOPS) study that enrolled 3047 men, there were 4 cases of breast cancer in men treated with finasteride 5 mg but no cases in men not treated with finasteride 5 mg. During the 4-year placebo-controlled long-term efficacy and safety study that enrolled 3040 men, there were 2 cases of breast cancer in placebo-treated men, but no cases were reported in men treated with finasteride 5 mg. During the 7-year placebo-controlled Prostate Cancer Prevention Trial (PCPT) that enrolled 18,882 men, there was 1 case of breast cancer in men treated with finasteride 5 mg, and 1 case of breast cancer in men treated with placebo. The relationship between long-term use of finasteride and male breast neoplasia is currently unknown. The PCPT trial was a 7-year randomized, double-blind, placebo-controlled trial that enrolled 18,882 healthy men ≥55 years of age with a normal digital rectal examination and a PSA ≤3 ng/mL. Men received either finasteride 5 mg or placebo daily. Patients were evaluated annually with PSA and digital rectal exams. Biopsies were performed for elevated PSA, an abnormal digital rectal exam, or the end of study. The incidence of Gleason score 8 to 10 prostate cancer was higher in men treated with finasteride (1.8%) than in those treated with placebo (1.1%). In a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor [AVODART (dutasteride)], similar results for Gleason score 8 to 10 prostate cancer were observed (1% dutasteride vs. 0.5% placebo). The clinical significance of these findings with respect to use of finasteride by men is unknown. No clinical benefit has been demonstrated in patients with prostate cancer treated with finasteride 5 mg. Finasteride 5 mg is not approved to reduce the risk of developing prostate cancer. Sexual Function Questionnaire A sexual function questionnaire was self-administered by patients participating in the two vertex baldness trials to detect more subtle changes in sexual function.

state cancer treated with finasteride 5 mg. Finasteride 5 mg is not approved to reduce the risk of developing prostate cancer. Sexual Function Questionnaire A sexual function questionnaire was self-administered by patients participating in the two vertex baldness trials to detect more subtle changes in sexual function. At Month 12, statistically significant differences in favor of placebo were found in 3 of 4 domains (sexual interest, erections, and perception of sexual problems). However, no significant difference was seen in the question on overall satisfaction with sex life. In one of the two vertex baldness studies, patients were questioned on non-scalp body hair growth. Finasteride did not appear to affect non-scalp body hair. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of finasteride. 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: Hypersensitivity Reaction: hypersensitivity reactions such as rash, pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face); Reproductive System: sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, libido disorders, ejaculation disorders, and orgasm disorders; male infertility and/or poor seminal quality (normalization or improvement of seminal quality has been reported after discontinuation of finasteride); testicular pain; hematospermia. Neoplasms: male breast cancer; Breast Disorders: breast tenderness and enlargement; Nervous System/Psychiatric: depression, suicidal ideation and behavior.

<table ID="_RefID0ENKAE" cellpadding="0pt" cellspacing="0pt" width="100%"><caption>TABLE 1: Drug-Related Adverse Experiences for Finasteride 1 mg in Year 1 (%) MALE PATTERN HAIR LOSS </caption><col width="40%"/><col width="30%"/><col width="30%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"/><td align="center" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Finasteride</content> <content styleCode="bold">N=945</content> </paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Placebo</content> <content styleCode="bold">N=934</content> </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Decreased Libido </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.8 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.3 </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Erectile Dysfunction </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.3 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.7 </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Ejaculation Disorder <content styleCode="italics"> (Decreased Volume of Ejaculate)</content> </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.2 <content styleCode="italics">(0.8)</content> </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.7 <content styleCode="italics">(0.4)</content> </paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>Discontinuation due to drug-related sexual adverse experiences </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.2 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.9 </paragraph></td></tr></tbody></table>

e " valign="middle"><paragraph>Discontinuation due to drug-related sexual adverse experiences </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.2 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.9 </paragraph></td></tr></tbody></table> <table ID="_RefID0E1OAE" cellpadding="0pt" cellspacing="0pt" width="100%"><caption>TABLE 2: Drug-Related Adverse Experiences for Finasteride 5 mg BENIGN PROSTATIC HYPERPLASIA</caption><col width="25%"/><col width="25%"/><col width="25%"/><col width="12%"/><col width="12%"/><tfoot><tr><td align="left" colspan="5" valign="top">*Combined Years 2 to 4 N = 1524 and 1516, finasteride vs.

th="100%"><caption>TABLE 2: Drug-Related Adverse Experiences for Finasteride 5 mg BENIGN PROSTATIC HYPERPLASIA</caption><col width="25%"/><col width="25%"/><col width="25%"/><col width="12%"/><col width="12%"/><tfoot><tr><td align="left" colspan="5" valign="top">*Combined Years 2 to 4 N = 1524 and 1516, finasteride vs. placebo, respectively </td></tr></tfoot><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph> </paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Year 1</content> <content styleCode="bold">(%)</content> </paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Years 2, 3 and 4*</content> <content styleCode="bold">(%)</content> </paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Finasteride </content> <content styleCode="bold">5 mg</content> </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo</content> </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">Finasteride </content> <content styleCode="bold">5 mg</content> </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo</content> </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Impotence </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>8.1 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3.7 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5.1 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5.1 </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Decreased Libido </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6.4 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3.4 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2.6 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2.6 </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Decreased Volume of Ejaculate </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3.7 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.8 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.5 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.5 </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Ejaculation Disorder </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.8 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.1 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.2 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.1 </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Breast Enlargement </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.5 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.1 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.8 </para

"><paragraph>Breast Enlargement </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.5 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.1 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.8 </para graph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.1 </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Breast Tenderness </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.4 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.1 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.7 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.3 </paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>Rash </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.5 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.2 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.5 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.1 </paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS 7.1 Cytochrome P450-Linked Drug Metabolizing Enzyme System No drug interactions of clinical importance have been identified. Finasteride does not appear to affect the cytochrome P450-linked drug-metabolizing enzyme system. Compounds that have been tested in man include antipyrine, digoxin, propranolol, theophylline, and warfarin and no clinically meaningful interactions were found. 7.2 Other Concomitant Therapy Although specific interaction studies were not performed, finasteride doses of 1 mg or more were concomitantly used in clinical studies with acetaminophen, acetylsalicylic acid, α-blockers, analgesics, angiotensin-converting enzyme (ACE) inhibitors, anticonvulsants, benzodiazepines, beta blockers, calcium-channel blockers, cardiac nitrates, diuretics, H 2 antagonists, HMG-CoA reductase inhibitors, prostaglandin synthetase inhibitors (also referred to as NSAIDs), and quinolone anti-infectives without evidence of clinically significant adverse interactions.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category X [see Contraindications (4) ] . Finasteride is contraindicated for use in women who are or may become pregnant. Finasteride is a Type II 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. In animal studies, finasteride caused abnormal development of external genitalia in male fetuses. 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 the male fetus. Abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (DHT) is inhibited by 5α-reductase inhibitors. These outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. Women could be exposed to finasteride through contact with crushed or broken finasteride tablets or semen from a male partner taking finasteride. With regard to finasteride exposure through the skin, finasteride tablets are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. Women who are pregnant or may become pregnant should not handle crushed or broken finasteride tablets because of possible exposure of a male fetus. If a pregnant woman comes in contact with crushed or broken finasteride tablets, the contact area should be washed immediately with soap and water. With regard to potential finasteride exposure through semen, a study has been conducted in men receiving finasteride 1 mg/day that measured finasteride concentrations in semen [see Clinical Pharmacology (12.3) ] . In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). At maternal doses of oral finasteride approximately 1 to 684 times the recommended human dose (RHD) of 1 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. Exposure multiples were estimated using data from nonpregnant rats. Days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia. At oral maternal doses approximately 0.2 times the RHD (based on AUC at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. Decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.02 times the RHD (based on AUC at animal dose of 0.003 mg/kg/day). No abnormalities were observed in female offspring exposed to any dose of finasteride in utero . No developmental abnormalities were observed in the offspring of untreated females mated with finasteride-treated male rats that received approximately 488 times the RHD (based on AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 20 times the RHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. No effects on fertility were seen in female offspring under these conditions.

n AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 20 times the RHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. No effects on fertility were seen in female offspring under these conditions. No evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6 to 18) at maternal doses up to 100 mg/kg/day (finasteride exposure levels were not measured in rabbits). However, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. The fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20 to 100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. Intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/mL or about 930 times the highest estimated exposure of pregnant women to finasteride from semen of men taking 1 mg/day) resulted in no abnormalities in male fetuses. In confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 120,000 times the highest estimated blood levels of finasteride from semen of men taking 1 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. No other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose. 8.3 Nursing Mothers Finasteride is not indicated for use in women. It is not known whether finasteride is excreted in human milk. 8.4 Pediatric Use Finasteride is not indicated for use in pediatric patients. Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical efficacy studies with finasteride did not include subjects aged 65 and over. Based on the pharmacokinetics of finasteride 5 mg, no dosage adjustment is necessary in the elderly for finasteride [see Clinical Pharmacology (12.3) ] . However the efficacy of finasteride in the elderly has not been established. 8.6 Hepatic Impairment Caution should be exercised in the administration of finasteride in those patients with liver function abnormalities, as finasteride is metabolized extensively in the liver [see Clinical Pharmacology (12.3) ] . 8.7 Renal Impairment No dosage adjustment is necessary in patients with renal impairment [see Clinical Pharmacology (12.3) ] .

8.1 Pregnancy Pregnancy Category X [see Contraindications (4) ] . Finasteride is contraindicated for use in women who are or may become pregnant. Finasteride is a Type II 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. In animal studies, finasteride caused abnormal development of external genitalia in male fetuses. 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 the male fetus. Abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (DHT) is inhibited by 5α-reductase inhibitors. These outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. Women could be exposed to finasteride through contact with crushed or broken finasteride tablets or semen from a male partner taking finasteride. With regard to finasteride exposure through the skin, finasteride tablets are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. Women who are pregnant or may become pregnant should not handle crushed or broken finasteride tablets because of possible exposure of a male fetus. If a pregnant woman comes in contact with crushed or broken finasteride tablets, the contact area should be washed immediately with soap and water. With regard to potential finasteride exposure through semen, a study has been conducted in men receiving finasteride 1 mg/day that measured finasteride concentrations in semen [see Clinical Pharmacology (12.3) ] . In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). At maternal doses of oral finasteride approximately 1 to 684 times the recommended human dose (RHD) of 1 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. Exposure multiples were estimated using data from nonpregnant rats. Days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia. At oral maternal doses approximately 0.2 times the RHD (based on AUC at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. Decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.02 times the RHD (based on AUC at animal dose of 0.003 mg/kg/day). No abnormalities were observed in female offspring exposed to any dose of finasteride in utero . No developmental abnormalities were observed in the offspring of untreated females mated with finasteride-treated male rats that received approximately 488 times the RHD (based on AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 20 times the RHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. No effects on fertility were seen in female offspring under these conditions.

n AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 20 times the RHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. No effects on fertility were seen in female offspring under these conditions. No evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6 to 18) at maternal doses up to 100 mg/kg/day (finasteride exposure levels were not measured in rabbits). However, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. The fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20 to 100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. Intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/mL or about 930 times the highest estimated exposure of pregnant women to finasteride from semen of men taking 1 mg/day) resulted in no abnormalities in male fetuses. In confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 120,000 times the highest estimated blood levels of finasteride from semen of men taking 1 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. No other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose.

8.5 Geriatric Use Clinical efficacy studies with finasteride did not include subjects aged 65 and over. Based on the pharmacokinetics of finasteride 5 mg, no dosage adjustment is necessary in the elderly for finasteride [see Clinical Pharmacology (12.3) ] . However the efficacy of finasteride in the elderly has not been established.

10 OVERDOSAGE In clinical studies, single doses of finasteride up to 400 mg and multiple doses of finasteride up to 80 mg/day for three months did not result in adverse reactions. Until further experience is obtained, no specific treatment for an overdose with finasteride can be recommended. Significant lethality was observed in male and female mice at single oral doses of 1500 mg/m 2 (500 mg/kg) and in female and male rats at single oral doses of 2360 mg/m 2 (400 mg/kg) and 5900 mg/m 2 (1000 mg/kg), respectively.

11 DESCRIPTION Finasteride tablets USP contain finasteride USP as the active ingredient. Finasteride, a synthetic 4-azasteroid compound, is a specific inhibitor of steroid Type II 5α-reductase, an intracellular enzyme that converts the androgen testosterone into 5α-dihydrotestosterone (DHT). The chemical name of finasteride is N-tert -Butyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide. The molecular formula of finasteride is C 23 H 36 N 2 O 2 and its molecular weight is 372.55. Its structural formula is: Finasteride USP is a white to off-white, crystalline solid with a melting point between 254°C and 262°C. It is freely soluble in chloroform and in lower alcohol solvents but is practically insoluble in water. Finasteride tablets USP are film-coated tablets for oral administration. Each tablet contains 1 mg of finasteride USP and the following inactive ingredients: docusate sodium, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinised starch (maize), sodium starch glycolate, talc, and titanium dioxide. Chemical Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Finasteride is a competitive and specific inhibitor of Type II 5α-reductase, an intracellular enzyme that converts the androgen testosterone into DHT. Two distinct isozymes are found in mice, rats, monkeys, and humans: Type I and II. Each of these isozymes is differentially expressed in tissues and developmental stages. In humans, Type I 5α-reductase is predominant in the sebaceous glands of most regions of skin, including scalp, and liver. Type I 5α-reductase is responsible for approximately one-third of circulating DHT. The Type II 5α-reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT. In humans, the mechanism of action of finasteride is based on its preferential inhibition of the Type II isozyme. Using native tissues (scalp and prostate), in vitro binding studies examining the potential of finasteride to inhibit either isozyme revealed a 100-fold selectivity for the human Type II 5α-reductase over Type I isozyme (IC 50 =500 and 4.2 nM for Type I and II, respectively). For both isozymes, the inhibition by finasteride is accompanied by reduction of the inhibitor to dihydrofinasteride and adduct formation with NADP+. The turnover for the enzyme complex is slow (t 1/2 approximately 30 days for the Type II enzyme complex and 14 days for the Type I complex). Inhibition of Type II 5α-reductase blocks the peripheral conversion of testosterone to DHT, resulting in significant decreases in serum and tissue DHT concentrations. In men with male pattern hair loss (androgenetic alopecia), the balding scalp contains miniaturized hair follicles and increased amounts of DHT compared with hairy scalp. Administration of finasteride decreases scalp and serum DHT concentrations in these men. The relative contributions of these reductions to the treatment effect of finasteride have not been defined. By this mechanism, finasteride appears to interrupt a key factor in the development of androgenetic alopecia in those patients genetically predisposed. 12.2 Pharmacodynamics Finasteride produces a rapid reduction in serum DHT concentration, reaching 65% suppression within 24 hours of oral dosing with a 1 mg tablet. Mean circulating levels of testosterone and estradiol were increased by approximately 15% as compared to baseline, but these remained within the physiologic range. Finasteride has no affinity for the androgen receptor and has no androgenic, antiandrogenic, estrogenic, antiestrogenic, or progestational effects. The relationship between these pharmacodynamic activities and the mechanisms(s) by which finasteride exerts its clinical effect is unknown. In studies with finasteride, no clinically meaningful changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH) or prolactin were detected. In healthy volunteers, treatment with finasteride did not alter the response of LH and FSH to gonadotropin-releasing hormone indicating that the hypothalamic-pituitary-testicular axis was not affected. Finasteride had no effect on circulating levels of cortisol, thyroid-stimulating hormone, or thyroxine, nor did it affect the plasma lipid profile (e.g., total cholesterol, low-density lipoproteins, high-density lipoproteins and triglycerides) or bone mineral density.

halamic-pituitary-testicular axis was not affected. Finasteride had no effect on circulating levels of cortisol, thyroid-stimulating hormone, or thyroxine, nor did it affect the plasma lipid profile (e.g., total cholesterol, low-density lipoproteins, high-density lipoproteins and triglycerides) or bone mineral density. 12.3 Pharmacokinetics Absorption In a study in 15 healthy young male subjects, the mean bioavailability of finasteride 1 mg tablets was 65% (range 26 to 170%), based on the ratio of area under the curve (AUC) relative to an intravenous (IV) reference dose. At steady state following dosing with 1 mg/day (n=12), maximum finasteride plasma concentration averaged 9.2 ng/mL (range, 4.9 to 13.7 ng/mL) and was reached 1 to 2 hours postdose; AUC (0-24 hr) was 53 ng•hr/mL (range, 20 to 154 ng•hr/mL). Bioavailability of finasteride was not affected by food. Distribution Mean steady-state volume of distribution was 76 liters (range, 44 to 96 liters; n=15). Approximately 90% of circulating finasteride is bound to plasma proteins. There is a slow accumulation phase for finasteride after multiple dosing. Finasteride has been found to cross the blood-brain barrier. Semen levels have been measured in 35 men taking finasteride 1 mg/day for 6 weeks. In 60% (21 of 35) of the samples, finasteride levels were undetectable (<0.2 ng/mL). The mean finasteride level was 0.26 ng/mL and the highest level measured was 1.52 ng/mL. Using the highest semen level measured and assuming 100% absorption from a 5 mL ejaculate per day, human exposure through vaginal absorption would be up to 7.6 ng per day, which is 650-fold less than the dose of finasteride (5 mcg) that had no effect on circulating DHT levels in men. [See Use in Specific Populations (8.1) .] Metabolism Finasteride is extensively metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme subfamily. Two metabolites, the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites, have been identified that possess no more than 20% of the 5α-reductase inhibitory activity of finasteride. Excretion Following intravenous infusion in healthy young subjects (n=15), mean plasma clearance of finasteride was 165 mL/min (range, 70 to 279 mL/min). Mean terminal half-life in plasma was 4.5 hours (range, 3.3 to 13.4 hours; n=12). Following an oral dose of 14 C-finasteride in man (n=6), a mean of 39% (range, 32 to 46%) of the dose was excreted in the urine in the form of metabolites; 57% (range, 51 to 64%) was excreted in the feces. Mean terminal half-life is approximately 5 to 6 hours in men 18 to 60 years of age and 8 hours in men more than 70 years of age. TABLE 3: Mean (SD) Pharmacokinetic Parameters in Healthy Men (ages 18 to 26) Mean (± SD) n=15 *Range Bioavailability 65% (26 to 170%)* Clearance (mL/min) 165 (55) Volume of Distribution (L) 76 (14) TABLE 4: Mean (SD) Noncompartmental Pharmacokinetic Parameters After Multiple Doses of 1 mg/day in Healthy Men (ages 19 to 42) Mean (± SD) (n=12) *First-dose values; all other parameters are last-dose values AUC (ng•hr/mL) 53 (33.8) Peak Concentration (ng/mL) 9.2 (2.6) Time to Peak (hours) 1.3 (0.5) Half-Life (hours)* 4.5 (1.6) Renal Impairment No dosage adjustment is necessary in patients with renal impairment. In patients with chronic renal impairment, with creatinine clearances ranging from 9 to 55 mL/min, AUC, maximum plasma concentration, half-life, and protein binding after a single dose of 14 C-finasteride were similar to those obtained in healthy volunteers. Urinary excretion of metabolites was decreased in patients with renal impairment. This decrease was associated with an increase in fecal excretion of metabolites.

C, maximum plasma concentration, half-life, and protein binding after a single dose of 14 C-finasteride were similar to those obtained in healthy volunteers. Urinary excretion of metabolites was decreased in patients with renal impairment. This decrease was associated with an increase in fecal excretion of metabolites. Plasma concentrations of metabolites were significantly higher in patients with renal impairment (based on a 60% increase in total radioactivity AUC). However, finasteride has been tolerated in men with normal renal function receiving up to 80 mg/day for 12 weeks where exposure of these patients to metabolites would presumably be much greater. Hepatic Impairment The effect of hepatic impairment on finasteride pharmacokinetics has not been studied. Caution should be used in the administration of finasteride in patients with liver function abnormalities, as finasteride is metabolized extensively in the liver.

12.1 Mechanism of Action Finasteride is a competitive and specific inhibitor of Type II 5α-reductase, an intracellular enzyme that converts the androgen testosterone into DHT. Two distinct isozymes are found in mice, rats, monkeys, and humans: Type I and II. Each of these isozymes is differentially expressed in tissues and developmental stages. In humans, Type I 5α-reductase is predominant in the sebaceous glands of most regions of skin, including scalp, and liver. Type I 5α-reductase is responsible for approximately one-third of circulating DHT. The Type II 5α-reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT. In humans, the mechanism of action of finasteride is based on its preferential inhibition of the Type II isozyme. Using native tissues (scalp and prostate), in vitro binding studies examining the potential of finasteride to inhibit either isozyme revealed a 100-fold selectivity for the human Type II 5α-reductase over Type I isozyme (IC 50 =500 and 4.2 nM for Type I and II, respectively). For both isozymes, the inhibition by finasteride is accompanied by reduction of the inhibitor to dihydrofinasteride and adduct formation with NADP+. The turnover for the enzyme complex is slow (t 1/2 approximately 30 days for the Type II enzyme complex and 14 days for the Type I complex). Inhibition of Type II 5α-reductase blocks the peripheral conversion of testosterone to DHT, resulting in significant decreases in serum and tissue DHT concentrations. In men with male pattern hair loss (androgenetic alopecia), the balding scalp contains miniaturized hair follicles and increased amounts of DHT compared with hairy scalp. Administration of finasteride decreases scalp and serum DHT concentrations in these men. The relative contributions of these reductions to the treatment effect of finasteride have not been defined. By this mechanism, finasteride appears to interrupt a key factor in the development of androgenetic alopecia in those patients genetically predisposed.

12.2 Pharmacodynamics Finasteride produces a rapid reduction in serum DHT concentration, reaching 65% suppression within 24 hours of oral dosing with a 1 mg tablet. Mean circulating levels of testosterone and estradiol were increased by approximately 15% as compared to baseline, but these remained within the physiologic range. Finasteride has no affinity for the androgen receptor and has no androgenic, antiandrogenic, estrogenic, antiestrogenic, or progestational effects. The relationship between these pharmacodynamic activities and the mechanisms(s) by which finasteride exerts its clinical effect is unknown. In studies with finasteride, no clinically meaningful changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH) or prolactin were detected. In healthy volunteers, treatment with finasteride did not alter the response of LH and FSH to gonadotropin-releasing hormone indicating that the hypothalamic-pituitary-testicular axis was not affected. Finasteride had no effect on circulating levels of cortisol, thyroid-stimulating hormone, or thyroxine, nor did it affect the plasma lipid profile (e.g., total cholesterol, low-density lipoproteins, high-density lipoproteins and triglycerides) or bone mineral density.

12.3 Pharmacokinetics Absorption In a study in 15 healthy young male subjects, the mean bioavailability of finasteride 1 mg tablets was 65% (range 26 to 170%), based on the ratio of area under the curve (AUC) relative to an intravenous (IV) reference dose. At steady state following dosing with 1 mg/day (n=12), maximum finasteride plasma concentration averaged 9.2 ng/mL (range, 4.9 to 13.7 ng/mL) and was reached 1 to 2 hours postdose; AUC (0-24 hr) was 53 ng•hr/mL (range, 20 to 154 ng•hr/mL). Bioavailability of finasteride was not affected by food. Distribution Mean steady-state volume of distribution was 76 liters (range, 44 to 96 liters; n=15). Approximately 90% of circulating finasteride is bound to plasma proteins. There is a slow accumulation phase for finasteride after multiple dosing. Finasteride has been found to cross the blood-brain barrier. Semen levels have been measured in 35 men taking finasteride 1 mg/day for 6 weeks. In 60% (21 of 35) of the samples, finasteride levels were undetectable (<0.2 ng/mL). The mean finasteride level was 0.26 ng/mL and the highest level measured was 1.52 ng/mL. Using the highest semen level measured and assuming 100% absorption from a 5 mL ejaculate per day, human exposure through vaginal absorption would be up to 7.6 ng per day, which is 650-fold less than the dose of finasteride (5 mcg) that had no effect on circulating DHT levels in men. [See Use in Specific Populations (8.1) .] Metabolism Finasteride is extensively metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme subfamily. Two metabolites, the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites, have been identified that possess no more than 20% of the 5α-reductase inhibitory activity of finasteride. Excretion Following intravenous infusion in healthy young subjects (n=15), mean plasma clearance of finasteride was 165 mL/min (range, 70 to 279 mL/min). Mean terminal half-life in plasma was 4.5 hours (range, 3.3 to 13.4 hours; n=12). Following an oral dose of 14 C-finasteride in man (n=6), a mean of 39% (range, 32 to 46%) of the dose was excreted in the urine in the form of metabolites; 57% (range, 51 to 64%) was excreted in the feces. Mean terminal half-life is approximately 5 to 6 hours in men 18 to 60 years of age and 8 hours in men more than 70 years of age. TABLE 3: Mean (SD) Pharmacokinetic Parameters in Healthy Men (ages 18 to 26) Mean (± SD) n=15 *Range Bioavailability 65% (26 to 170%)* Clearance (mL/min) 165 (55) Volume of Distribution (L) 76 (14) TABLE 4: Mean (SD) Noncompartmental Pharmacokinetic Parameters After Multiple Doses of 1 mg/day in Healthy Men (ages 19 to 42) Mean (± SD) (n=12) *First-dose values; all other parameters are last-dose values AUC (ng•hr/mL) 53 (33.8) Peak Concentration (ng/mL) 9.2 (2.6) Time to Peak (hours) 1.3 (0.5) Half-Life (hours)* 4.5 (1.6) Renal Impairment No dosage adjustment is necessary in patients with renal impairment. In patients with chronic renal impairment, with creatinine clearances ranging from 9 to 55 mL/min, AUC, maximum plasma concentration, half-life, and protein binding after a single dose of 14 C-finasteride were similar to those obtained in healthy volunteers. Urinary excretion of metabolites was decreased in patients with renal impairment. This decrease was associated with an increase in fecal excretion of metabolites.

<table ID="_RefID0EUHAG" cellpadding="0pt" cellspacing="0pt" width="100%"><caption>TABLE 3: Mean (SD) Pharmacokinetic Parameters in Healthy Men (ages 18 to 26) </caption><col width="54%"/><col width="46%"/><thead><tr><th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="top"/><th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="top"><content styleCode="bold">Mean (&#xB1; SD)</content> <content styleCode="bold">n=15</content></th></tr></thead><tfoot><tr><td align="left" colspan="2" valign="top">*Range </td></tr></tfoot><tbody><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph> Bioavailability </paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph> 65% (26 to 170%)* </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Clearance (mL/min) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> 165 (55) </paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Volume of Distribution (L) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph> 76 (14) </paragraph></td></tr></tbody></table>

er" styleCode="Rrule Botrule " valign="top"><paragraph> 165 (55) </paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Volume of Distribution (L) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph> 76 (14) </paragraph></td></tr></tbody></table> <table ID="_RefID0EVJAG" cellpadding="0pt" cellspacing="0pt" width="100%"><caption>TABLE 4: Mean (SD) Noncompartmental Pharmacokinetic Parameters After Multiple Doses of 1 mg/day in Healthy Men (ages 19 to 42) </caption><col width="53%"/><col width="47%"/><thead><tr><th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="top"><content styleCode="bold"> </content></th><th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="top"><content styleCode="bold">Mean (&#xB1; SD)</content> <content styleCode="bold">(n=12)</content></th></tr></thead><tfoot><tr><td align="left" colspan="2" valign="top">*First-dose values; all other parameters are last-dose values </td></tr></tfoot><tbody><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="bottom"><paragraph> AUC (ng&#x2022;hr/mL) </paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>53 (33.8) </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Peak Concentration (ng/mL) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>9.2 (2.6) </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Time to Peak (hours) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.3 (0.5) </paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Half-Life (hours)* </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4.5 (1.6) </paragraph></td></tr></tbody></table>

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No evidence of a tumorigenic effect was observed in a 24-month study in Sprague-Dawley rats receiving doses of finasteride up to 160 mg/kg/day in males and 320 mg/kg/day in females. These doses produced respective systemic exposure in rats of 888 and 2192 times those observed in man receiving the recommended human dose of 1 mg/day. All exposure calculations were based on calculated AUC (0-24 hr) for animals and mean AUC (0-24 hr) for man (0.05 mcg•hr/mL). In a 19-month carcinogenicity study in CD-1 mice, a statistically significant (p≤0.05) increase in the incidence of testicular Leydig cell adenomas was observed at 1824 times the human exposure (250 mg/kg/day). In mice at 184 times the human exposure, estimated (25 mg/kg/day) and in rats at 312 times the human exposure (≥40 mg/kg/day) an increase in the incidence of Leydig cell hyperplasia was observed. A positive correlation between the proliferative changes in the Leydig cells and an increase in serum LH levels (2- to 3-fold above control) has been demonstrated in both rodent species treated with high doses of finasteride. No drug-related Leydig cell changes were seen in either rats or dogs treated with finasteride for 1 year at 240 and 2800 times (20 mg/kg/day and 45 mg/kg/day, respectively), or in mice treated for 19 months at 18.4 times the human exposure, estimated (2.5 mg/kg/day). No evidence of mutagenicity was observed in an in vitro bacterial mutagenesis assay, a mammalian cell mutagenesis assay, or in an in vitro alkaline elution assay. In an in vitro chromosome aberration assay, using Chinese hamster ovary cells, there was a slight increase in chromosome aberrations. In an in vivo chromosome aberration assay in mice, no treatment-related increase in chromosome aberration was observed with finasteride at the maximum tolerated dose of 250 mg/kg/day (1824 times the human exposure) as determined in the carcinogenicity studies. In sexually mature male rabbits treated with finasteride at 4344 times the human exposure (80 mg/kg/day) for up to 12 weeks, no effect on fertility, sperm count, or ejaculate volume was seen. In sexually mature male rats treated with 488 times the human exposure (80 mg/kg/day), there were no significant effects on fertility after 6 or 12 weeks of treatment; however, when treatment was continued for up to 24 or 30 weeks, there was an apparent decrease in fertility, fecundity, and an associated significant decrease in the weights of the seminal vesicles and prostate. All these effects were reversible within 6 weeks of discontinuation of treatment. No drug-related effect on testes or on mating performance has been seen in rats or rabbits. This decrease in fertility in finasteride-treated rats is secondary to its effect on accessory sex organs (prostate and seminal vesicles) resulting in failure to form a seminal plug. The seminal plug is essential for normal fertility in rats but is not relevant in man.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No evidence of a tumorigenic effect was observed in a 24-month study in Sprague-Dawley rats receiving doses of finasteride up to 160 mg/kg/day in males and 320 mg/kg/day in females. These doses produced respective systemic exposure in rats of 888 and 2192 times those observed in man receiving the recommended human dose of 1 mg/day. All exposure calculations were based on calculated AUC (0-24 hr) for animals and mean AUC (0-24 hr) for man (0.05 mcg•hr/mL). In a 19-month carcinogenicity study in CD-1 mice, a statistically significant (p≤0.05) increase in the incidence of testicular Leydig cell adenomas was observed at 1824 times the human exposure (250 mg/kg/day). In mice at 184 times the human exposure, estimated (25 mg/kg/day) and in rats at 312 times the human exposure (≥40 mg/kg/day) an increase in the incidence of Leydig cell hyperplasia was observed. A positive correlation between the proliferative changes in the Leydig cells and an increase in serum LH levels (2- to 3-fold above control) has been demonstrated in both rodent species treated with high doses of finasteride. No drug-related Leydig cell changes were seen in either rats or dogs treated with finasteride for 1 year at 240 and 2800 times (20 mg/kg/day and 45 mg/kg/day, respectively), or in mice treated for 19 months at 18.4 times the human exposure, estimated (2.5 mg/kg/day). No evidence of mutagenicity was observed in an in vitro bacterial mutagenesis assay, a mammalian cell mutagenesis assay, or in an in vitro alkaline elution assay. In an in vitro chromosome aberration assay, using Chinese hamster ovary cells, there was a slight increase in chromosome aberrations. In an in vivo chromosome aberration assay in mice, no treatment-related increase in chromosome aberration was observed with finasteride at the maximum tolerated dose of 250 mg/kg/day (1824 times the human exposure) as determined in the carcinogenicity studies. In sexually mature male rabbits treated with finasteride at 4344 times the human exposure (80 mg/kg/day) for up to 12 weeks, no effect on fertility, sperm count, or ejaculate volume was seen. In sexually mature male rats treated with 488 times the human exposure (80 mg/kg/day), there were no significant effects on fertility after 6 or 12 weeks of treatment; however, when treatment was continued for up to 24 or 30 weeks, there was an apparent decrease in fertility, fecundity, and an associated significant decrease in the weights of the seminal vesicles and prostate. All these effects were reversible within 6 weeks of discontinuation of treatment. No drug-related effect on testes or on mating performance has been seen in rats or rabbits. This decrease in fertility in finasteride-treated rats is secondary to its effect on accessory sex organs (prostate and seminal vesicles) resulting in failure to form a seminal plug. The seminal plug is essential for normal fertility in rats but is not relevant in man.

14 CLINICAL STUDIES 14.1 Studies in Men The efficacy of finasteride was demonstrated in men (88% Caucasian) with mild to moderate androgenetic alopecia (male pattern hair loss) between 18 and 41 years of age. In order to prevent seborrheic dermatitis which might confound the assessment of hair growth in these studies, all men, whether treated with finasteride or placebo, were instructed to use a specified, medicated, tar-based shampoo (Neutrogena T/Gel ® Shampoo) during the first 2 years of the studies. There were three double-blind, randomized, placebo-controlled studies of 12-month duration. The two primary endpoints were hair count and patient self-assessment; the two secondary endpoints were investigator assessment and ratings of photographs. In addition, information was collected regarding sexual function (based on a self-administered questionnaire) and non-scalp body hair growth. The three studies were conducted in 1879 men with mild to moderate, but not complete, hair loss. Two of the studies enrolled men with predominantly mild to moderate vertex hair loss (n=1553). The third enrolled men having mild to moderate hair loss in the anterior mid-scalp area with or without vertex balding (n=326). Studies in Men with Vertex Baldness Of the men who completed the first 12 months of the two vertex baldness trials, 1215 elected to continue in double-blind, placebo-controlled, 12-month extension studies. There were 547 men receiving finasteride for both the initial study and first extension periods (up to 2 years of treatment) and 60 men receiving placebo for the same periods. The extension studies were continued for 3 additional years, with 323 men on finasteride and 23 on placebo entering the fifth year of the study. In order to evaluate the effect of discontinuation of therapy, there were 65 men who received finasteride for the initial 12 months followed by placebo in the first 12-month extension period. Some of these men continued in additional extension studies and were switched back to treatment with finasteride, with 32 men entering the fifth year of the study. Lastly, there were 543 men who received placebo for the initial 12 months followed by finasteride in the first 12-month extension period. Some of these men continued in additional extension studies receiving finasteride, with 290 men entering the fifth year of the study (see Figure 1 below). Hair counts were assessed by photographic enlargements of a representative area of active hair loss. In these two studies in men with vertex baldness, significant increases in hair count were demonstrated at 6 and 12 months in men treated with finasteride, while significant hair loss from baseline was demonstrated in those treated with placebo. At 12 months there was a 107-hair difference from placebo (p<0.001, finasteride [n=679] vs. placebo [n=672]) within a 1-inch diameter circle (5.1 cm 2 ). Hair count was maintained in those men taking finasteride for up to 2 years, resulting in a 138-hair difference between treatment groups (p<0.001, finasteride [n=433] vs. placebo [n=47]) within the same area. In men treated with finasteride, the maximum improvement in hair count compared to baseline was achieved during the first 2 years. Although the initial improvement was followed by a slow decline, hair count was maintained above baseline throughout the 5 years of the studies.

3] vs. placebo [n=47]) within the same area. In men treated with finasteride, the maximum improvement in hair count compared to baseline was achieved during the first 2 years. Although the initial improvement was followed by a slow decline, hair count was maintained above baseline throughout the 5 years of the studies. Furthermore, because the decline in the placebo group was more rapid, the difference between treatment groups also continued to increase throughout the studies, resulting in a 277-hair difference (p<0.001, finasteride [n=219] vs. placebo [n=15]) at 5 years (see Figure 1 below). Patients who switched from placebo to finasteride (n=425) had a decrease in hair count at the end of the initial 12-month placebo period, followed by an increase in hair count after 1 year of treatment with finasteride. This increase in hair count was less (56 hairs above original baseline) than the increase (91 hairs above original baseline) observed after 1 year of treatment in men initially randomized to finasteride. Although the increase in hair count, relative to when therapy was initiated, was comparable between these two groups, a higher absolute hair count was achieved in patients who were started on treatment with finasteride in the initial study. This advantage was maintained through the remaining 3 years of the studies. A change of treatment from finasteride to placebo (n=48) at the end of the initial 12 months resulted in reversal of the increase in hair count 12 months later, at 24 months (see Figure 1 below). At 12 months, 58% of men in the placebo group had further hair loss (defined as any decrease in hair count from baseline), compared with 14% of men treated with finasteride. In men treated for up to 2 years, 72% of men in the placebo group demonstrated hair loss, compared with 17% of men treated with finasteride. At 5 years, 100% of men in the placebo group demonstrated hair loss, compared with 35% of men treated with finasteride. Figure 1 Patient self-assessment was obtained at each clinic visit from a self-administered questionnaire, which included questions on their perception of hair growth, hair loss, and appearance. This self-assessment demonstrated an increase in amount of hair, a decrease in hair loss, and improvement in appearance in men treated with finasteride. Overall improvement compared with placebo was seen as early as 3 months (p<0.05), with improvement maintained over 5 years. Investigator assessment was based on a 7-point scale evaluating increases or decreases in scalp hair at each patient visit. This assessment showed significantly greater increases in hair growth in men treated with finasteride compared with placebo as early as 3 months (p<0.001). At 12 months, the investigators rated 65% of men treated with finasteride as having increased hair growth compared with 37% in the placebo group. At 2 years, the investigators rated 80% of men treated with finasteride as having increased hair growth compared with 47% of men treated with placebo. At 5 years, the investigators rated 77% of men treated with finasteride as having increased hair growth, compared with 15% of men treated with placebo. An independent panel rated standardized photographs of the head in a blinded fashion based on increases or decreases in scalp hair using the same 7-point scale as the investigator assessment. At 12 months, 48% of men treated with finasteride had an increase as compared with 7% of men treated with placebo. At 2 years, an increase in hair growth was demonstrated in 66% of men treated with finasteride, compared with 7% of men treated with placebo.

ir using the same 7-point scale as the investigator assessment. At 12 months, 48% of men treated with finasteride had an increase as compared with 7% of men treated with placebo. At 2 years, an increase in hair growth was demonstrated in 66% of men treated with finasteride, compared with 7% of men treated with placebo. At 5 years, 48% of men treated with finasteride demonstrated an increase in hair growth, 42% were rated as having no change (no further visible progression of hair loss from baseline) and 10% were rated as having lost hair when compared to baseline. In comparison, 6% of men treated with placebo demonstrated an increase in hair growth, 19% were rated as having no change and 75% were rated as having lost hair when compared to baseline. A 48-week, placebo-controlled study designed to assess by phototrichogram the effect of finasteride on total and actively growing (anagen) scalp hairs in vertex baldness enrolled 212 men with androgenetic alopecia. At baseline and 48 weeks, total and anagen hair counts were obtained in a 1 cm 2 target area of the scalp. Men treated with finasteride showed increases from baseline in total and anagen hair counts of 7 hairs and 18 hairs, respectively, whereas men treated with placebo had decreases of 10 hairs and 9 hairs, respectively. These changes in hair counts resulted in a between-group difference of 17 hairs in total hair count (p<0.001) and 27 hairs in anagen hair count (p<0.001), and an improvement in the proportion of anagen hairs from 62% at baseline to 68% for men treated with finasteride. Study in Men with Hair Loss in the Anterior Mid-Scalp Area A study of 12-month duration, designed to assess the efficacy of finasteride in men with hair loss in the anterior mid-scalp area, also demonstrated significant increases in hair count compared with placebo. Increases in hair count were accompanied by improvements in patient self-assessment, investigator assessment, and ratings based on standardized photographs. Hair counts were obtained in the anterior mid-scalp area, and did not include the area of bitemporal recession or the anterior hairline. Summary of Clinical Studies in Men Clinical studies were conducted in men aged 18 to 41 with mild to moderate degrees of androgenetic alopecia. All men treated with finasteride or placebo received a tar-based shampoo (Neutrogena T/Gel ® Shampoo) during the first 2 years of the studies. Clinical improvement was seen as early as 3 months in the patients treated with finasteride and led to a net increase in scalp hair count and hair regrowth. In clinical studies for up to 5 years, treatment with finasteride slowed the further progression of hair loss observed in the placebo group. In general, the difference between treatment groups continued to increase throughout the 5 years of the studies. Ethnic Analysis of Clinical Data from Men In a combined analysis of the two studies on vertex baldness, mean hair count changes from baseline were 91 vs. -19 hairs (finasteride vs. placebo) among Caucasians (n=1185), 49 vs. -27 hairs among Blacks (n=84), 53 vs. -38 hairs among Asians (n=17), 67 vs. 5 hairs among Hispanics (n=45) and 67 vs. -15 hairs among other ethnic groups (n=20). Patient self-assessment showed improvement across racial groups with finasteride treatment, except for satisfaction of the frontal hairline and vertex in Black men, who were satisfied overall. Figure 1 14.2 Study in Women In a study involving 137 postmenopausal women with androgenetic alopecia who were treated with finasteride (n=67) or placebo (n=70) for 12 months, effectiveness could not be demonstrated.

t, except for satisfaction of the frontal hairline and vertex in Black men, who were satisfied overall. Figure 1 14.2 Study in Women In a study involving 137 postmenopausal women with androgenetic alopecia who were treated with finasteride (n=67) or placebo (n=70) for 12 months, effectiveness could not be demonstrated. There was no improvement in hair counts, patient self-assessment, investigator assessment, or ratings of standardized photographs in the women treated with finasteride when compared with the placebo group [see Indications and Usage (1) ] .

16 HOW SUPPLIED/STORAGE AND HANDLING Finasteride Tablets USP, 1 mg are white colored, octagonal, biconvex, film-coated tablets debossed with ‘J’ on one side and ‘81’ on the other side. Bottles of 30 NDC 68788-6875-3 Bottles of 60 NDC 68788-6875-6 Bottles of 90 NDC 68788-6875-9 Storage and Handling Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature]. Keep container closed and protect from moisture. Women should not handle crushed or broken finasteride tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Finasteride tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets are not broken or crushed [see Warnings and Precautions (5.1), Use in Specific Populations (8.1) and Patient Counseling Information (17) ] .

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Exposure of Women — Risk to Male Fetus Physicians should inform patients that women who are pregnant or may potentially be pregnant should not handle crushed or broken finasteride tablets because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Finasteride tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed. If a woman who is pregnant or may potentially be pregnant comes in contact with crushed or broken finasteride tablets, the contact area should be washed immediately with soap and water [see Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1) and How Supplied/Storage and Handling (16) ] . Increased Risk of High-Grade Prostate Cancer Patients should be informed that there was an increase in high-grade prostate cancer in men treated with 5α-reductase inhibitors indicated for BPH treatment, compared to those treated with placebo in studies looking at the use of these drugs to prevent prostate cancer [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ] . Sexual Adverse events Physicians should inform the patients that finasteride may cause symptoms of sexual dysfunction such as decreased libido, erectile dysfunction, and ejaculation disorder, including decreased ejaculate volume. Additional Instructions Physicians should instruct their patients to promptly report any changes in their breasts such as lumps, pain or nipple discharge. Breast changes including breast enlargement, tenderness and neoplasm have been reported [see Adverse Reactions (6.1) ] . Physicians should instruct their patients to read the patient package insert before starting therapy with finasteride and to read it again each time the prescription is renewed so that they are aware of current information for patients regarding finasteride. The brands listed are trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad–500 032, India Revised: 08/2022 Repackaged By: Preferred Pharmaceuticals Inc.

Patient Information Finasteride Tablets, USP (fin as' ter ide) Finasteride tablets are for use by MEN ONLY and should NOT be used by women or children. Read this Patient Information before you start taking finasteride tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment. What are finasteride tablets? Finasteride tablets are a prescription medicine used for the treatment of male pattern hair loss (androgenetic alopecia). It is not known if finasteride tablets work for a receding hairline on either side of and above your forehead (temporal area). Finasteride tablets are not for use by women and children. Who should not take finasteride tablets? Do not take finasteride tablets if you: • are pregnant or may become pregnant. Finasteride tablets may harm your unborn baby. o Finasteride tablets are coated and will prevent contact with the medicine during handling, as long as the tablets are not broken or crushed. Females who are pregnant or who may become pregnant should not come in contact with broken or crushed finasteride tablets. If a pregnant woman comes in contact with crushed or broken finasteride tablets, wash the contact area right away with soap and water. If a woman who is pregnant comes into contact with the active ingredient in finasteride tablets, a healthcare provider should be consulted. o If a woman who is pregnant with a male baby swallows or comes in contact with the medicine in finasteride tablets, the male baby may be born with sex organs that are not normal. • are allergic to any of the ingredients in finasteride tablets. See the end of this leaflet for a complete list of ingredients in finasteride tablets. What should I tell my healthcare provider before taking finasteride tablets? Before taking finasteride tablets, tell your healthcare provider if you: • have any other medical conditions, including problems with your prostate or liver Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take finasteride tablets? • Take finasteride tablets exactly as your healthcare provider tells you to take them. • You may take finasteride tablets with or without food. • If you forget to take finasteride tablets, do not take an extra tablet. Just take the next tablet as usual. Finasteride tablets will not work faster or better if you take them more than once a day. What are the possible side effects of finasteride tablets? • decrease in your blood Prostate Specific Antigen (PSA) levels. Finasteride tablets can affect a blood test called PSA (Prostate Specific Antigen) for the screening of prostate cancer. If you have a PSA test done you should tell your healthcare provider that you are taking finasteride tablets because finasteride tablets decreases PSA levels. Changes in PSA levels will need to be evaluated by your healthcare provider. Any increase in follow-up PSA levels from their lowest point may signal the presence of prostate cancer and should be evaluated, even if the test results are still within the normal range for men not taking finasteride tablets.

ses PSA levels. Changes in PSA levels will need to be evaluated by your healthcare provider. Any increase in follow-up PSA levels from their lowest point may signal the presence of prostate cancer and should be evaluated, even if the test results are still within the normal range for men not taking finasteride tablets. You should also tell your healthcare provider if you have not been taking finasteride tablets as prescribed because this may affect the PSA test results. For more information, talk to your healthcare provider. • There may be an increased risk of a more serious form of prostate cancer in men taking finasteride at 5 times the dose of finasteride tablets. The most common side effects of finasteride tablets include: • decrease in sex drive • trouble getting or keeping an erection • a decrease in the amount of semen The following have been reported in general use with finasteride tablets: • breast tenderness and enlargement. Tell your healthcare provider about any changes in your breasts such as lumps, pain or nipple discharge. • depression; • decrease in sex drive that continued after stopping the medication; • allergic reactions including rash, itching, hives and swelling of the lips, tongue, throat, and face; • problems with ejaculation that continued after stopping medication; • testicular pain; • difficulty in achieving an erection that continued after stopping the medication; • male infertility and/or poor quality of semen. • in rare cases, male breast cancer. 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 finasteride tablets. 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. How should I store finasteride tablets? • Store finasteride tablets at 20º to 25ºC (68º to 77ºF). • Keep finasteride tablets in a closed container and keep finasteride tablets dry (protect from moisture). Keep finasteride tablets and all medicines out of the reach of children. General information about the safe and effective use of finasteride tablets. Medicines are sometimes prescribed for purposes other than those listed in this Patient Information leaflet. Do not use finasteride tablets for a condition for which it was not prescribed. Do not give finasteride tablets to other people, even if they have the same symptoms you have. They may harm them. This Patient Information leaflet summarizes the most important information about finasteride tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about finasteride tablets that is written for health professionals. For more information, call 1-866-850-2876 . What are the ingredients in finasteride tablets? Active ingredient: finasteride. Inactive ingredients: docusate sodium, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinised starch (maize), sodium starch glycolate, talc, and titanium dioxide. This Patient Information has been approved by the U.S. Food and Drug Administration. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 08/2022 Repackaged By: Preferred Pharmaceuticals Inc.

1 INDICATIONS AND USAGE PROSCAR, is a 5α-reductase inhibitor, indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to ( 1.1 ): Improve symptoms Reduce the risk of acute urinary retention Reduce the risk of the need for surgery including transurethral resection of the prostate (TURP) and prostatectomy. PROSCAR administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of BPH (a confirmed ≥4 point increase in American Urological Association (AUA) symptom score) ( 1.2 ). Limitations of Use : PROSCAR is not approved for the prevention of prostate cancer ( 1.3 ). 1.1 Monotherapy PROSCAR ® is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to: - Improve symptoms - Reduce the risk of acute urinary retention - Reduce the risk of the need for surgery including transurethral resection of the prostate (TURP) and prostatectomy. 1.2 Combination with Alpha-Blocker PROSCAR administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of BPH (a confirmed ≥4 point increase in American Urological Association (AUA) symptom score). 1.3 Limitations of Use PROSCAR is not approved for the prevention of prostate cancer.

2 DOSAGE AND ADMINISTRATION PROSCAR may be administered with or without meals. PROSCAR may be administered with or without meals ( 2 ). Monotherapy: One tablet (5 mg) taken once a day ( 2.1 ). Combination with Doxazosin: One tablet (5 mg) taken once a day in combination with the alpha-blocker doxazosin ( 2.2 ). 2.1 Monotherapy The recommended dose of PROSCAR is one tablet (5 mg) taken once a day [see Clinical Studies (14.1) ] . 2.2 Combination with Alpha-Blocker The recommended dose of PROSCAR is one tablet (5 mg) taken once a day in combination with the alpha-blocker doxazosin [see Clinical Studies (14.2) ].

4 CONTRAINDICATIONS PROSCAR is contraindicated in the following: Hypersensitivity to any component of this medication. Pregnancy. Finasteride use is contraindicated in females when they are or may potentially be pregnant. Because of the ability of Type II 5α-reductase inhibitors to inhibit the conversion of testosterone to 5α-dihydrotestosterone (DHT), finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant female who receives finasteride. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant female should be apprised of the potential hazard to the male fetus. [See also Warnings and Precautions (5.3) , Use in Specific Populations (8.1) , and How Supplied/Storage and Handling (16) .] In female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring. Hypersensitivity to any components of this product ( 4 ). Females who are or may potentially be pregnant ( 4 , 5.3 , 8.1 , 16 ).

5 WARNINGS AND PRECAUTIONS PROSCAR reduces serum prostate specific antigen (PSA) levels by approximately 50%. However, any confirmed increase in PSA while on PROSCAR may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for men not taking a 5α-reductase inhibitor ( 5.1 ). PROSCAR may increase the risk of high-grade prostate cancer ( 5.2 , 6.1 ). Females should not handle crushed or broken PROSCAR tablets when they are pregnant or may potentially be pregnant due to potential risk to a male fetus ( 5.3 , 8.1 , 16 ). PROSCAR is not indicated for use in pediatric patients or females ( 5.4 , 8.1 , 8.2 , 8.4 , 12.3 ). Prior to initiating treatment with PROSCAR for BPH, consideration should be given to other urological conditions that may cause similar symptoms ( 5.6 ). 5.1 Effects on Prostate Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection In clinical studies, PROSCAR reduced serum PSA concentration by approximately 50% within six months of treatment. This decrease is predictable over the entire range of PSA values in patients with symptomatic BPH, although it may vary in individuals. For interpretation of serial PSAs in men taking PROSCAR, a new PSA baseline should be established at least six months after starting treatment and PSA monitored periodically thereafter. Any confirmed increase from the lowest PSA value while on PROSCAR may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5α-reductase inhibitor. Non-compliance with PROSCAR therapy may also affect PSA test results. To interpret an isolated PSA value in patients treated with PROSCAR for six months or more, PSA values should be doubled for comparison with normal ranges in untreated men. These adjustments preserve the utility of PSA to detect prostate cancer in men treated with PROSCAR. PROSCAR may also cause decreases in serum PSA in the presence of prostate cancer. The ratio of free to total PSA (percent free PSA) remains constant even under the influence of PROSCAR. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men undergoing finasteride therapy, no adjustment to its value appears necessary. 5.2 Increased Risk of High-Grade Prostate Cancer Men aged 55 and over with a normal digital rectal examination and PSA ≤3.0 ng/mL at baseline taking finasteride 5 mg/day in the 7-year Prostate Cancer Prevention Trial (PCPT) had an increased risk of Gleason score 8-10 prostate cancer (finasteride 1.8% vs placebo 1.1%). [See Indications and Usage (1.3) and Adverse Reactions (6.1) .] Similar results were observed in a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART) (1% dutasteride vs 0.5% placebo). 5α-reductase inhibitors may increase the risk of development of high-grade prostate cancer. Whether the effect of 5α-reductase inhibitors to reduce prostate volume, or study-related factors, impacted the results of these studies has not been established. 5.3 Exposure of Females — Risk to Male Fetus PROSCAR is contraindicated in pregnant females and in females who may potentially be pregnant and not indicated for use in females. Based on animal studies and the mechanism of action, PROSCAR may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female.

— Risk to Male Fetus PROSCAR is contraindicated in pregnant females and in females who may potentially be pregnant and not indicated for use in females. Based on animal studies and the mechanism of action, PROSCAR may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female. Females who are pregnant or may potentially be pregnant should not handle crushed or broken PROSCAR tablets. PROSCAR tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed. If a pregnant female comes in contact with crushed or broken PROSCAR tablets, the contact area should be washed immediately with soap and water. [See Contraindications (4) , Use in Specific Populations (8.1) , Clinical Pharmacology (12.1 and 12.3) , and How Supplied/Storage and Handling (16) .] 5.4 Pediatric Patients and Females PROSCAR is not indicated for use in pediatric patients [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3) ] or females [see also Warnings and Precautions (5.3) , Use in Specific Populations (8.1) , Clinical Pharmacology (12.3) , and How Supplied/Storage and Handling (16) ]. 5.5 Effect on Semen Characteristics Treatment with PROSCAR for 24 weeks to evaluate semen parameters in healthy male volunteers revealed no clinically meaningful effects on sperm concentration, mobility, morphology, or pH. A 0.6 mL (22.1%) median decrease in ejaculate volume with a concomitant reduction in total sperm per ejaculate was observed. These parameters remained within the normal range and were reversible upon discontinuation of therapy with an average time to return to baseline of 84 weeks. 5.6 Consideration of Other Urological Conditions Prior to initiating treatment with PROSCAR, consideration should be given to other urological conditions that may cause similar symptoms. In addition, prostate cancer and BPH may coexist. Patients with large residual urinary volume and/or severely diminished urinary flow should be carefully monitored for obstructive uropathy. These patients may not be candidates for finasteride therapy.

6 ADVERSE REACTIONS The drug-related adverse reactions, reported in ≥1% in patients treated with PROSCAR and greater than in patients treated with placebo over a 4-year study are: impotence, decreased libido, decreased volume of ejaculate, breast enlargement, breast tenderness and rash ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Organon LLC, a subsidiary of Organon & Co., at 1-844-674-3200 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 clinical practice. 4-Year Placebo-Controlled Study (PLESS) In PLESS, 1524 patients treated with PROSCAR and 1516 patients treated with placebo were evaluated for safety over a period of 4 years. The most frequently reported adverse reactions were related to sexual function. 3.7% (57 patients) treated with PROSCAR and 2.1% (32 patients) treated with placebo discontinued therapy as a result of adverse reactions related to sexual function, which are the most frequently reported adverse reactions. Table 1 presents the only clinical adverse reactions considered possibly, probably or definitely drug related by the investigator, for which the incidence on PROSCAR was ≥1% and greater than placebo over the 4 years of the study. In years 2-4 of the study, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder. Table 1: Drug-Related Adverse Experiences Year 1 (%) Years 2, 3 and 4 Combined Years 2-4 (%) Finasteride Placebo Finasteride Placebo N = 1524 and 1516, finasteride vs placebo, respectively Impotence 8.1 3.7 5.1 5.1 Decreased Libido 6.4 3.4 2.6 2.6 Decreased Volume of Ejaculate 3.7 0.8 1.5 0.5 Ejaculation Disorder 0.8 0.1 0.2 0.1 Breast Enlargement 0.5 0.1 1.8 1.1 Breast Tenderness 0.4 0.1 0.7 0.3 Rash 0.5 0.2 0.5 0.1 Phase III Studies and 5-Year Open Extensions The adverse experience profile in the 1-year, placebo-controlled, Phase III studies, the 5-year open extensions, and PLESS were similar. Medical Therapy of Prostatic Symptoms (MTOPS) Study In the MTOPS study, 3047 men with symptomatic BPH were randomized to receive PROSCAR 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), the combination of PROSCAR 5 mg/day and doxazosin 4 or 8 mg/day (n=786), or placebo (n=737) for 4 to 6 years. [See Clinical Studies (14.2) .] The incidence rates of drug-related adverse experiences reported by ≥2% of patients in any treatment group in the MTOPS Study are listed in Table 2 . The individual adverse effects which occurred more frequently in the combination group compared to either drug alone were: asthenia, postural hypotension, peripheral edema, dizziness, decreased libido, rhinitis, abnormal ejaculation, impotence and abnormal sexual function (see Table 2 ). Of these, the incidence of abnormal ejaculation in patients receiving combination therapy was comparable to the sum of the incidences of this adverse experience reported for the two monotherapies. Combination therapy with finasteride and doxazosin was associated with no new clinical adverse experience. Four patients in MTOPS reported the adverse experience breast cancer. Three of these patients were on finasteride only and one was on combination therapy.

his adverse experience reported for the two monotherapies. Combination therapy with finasteride and doxazosin was associated with no new clinical adverse experience. Four patients in MTOPS reported the adverse experience breast cancer. Three of these patients were on finasteride only and one was on combination therapy. [See Long-Term Data .] The MTOPS Study was not specifically designed to make statistical comparisons between groups for reported adverse experiences. In addition, direct comparisons of safety data between the MTOPS study and previous studies of the single agents may not be appropriate based upon differences in patient population, dosage or dose regimen, and other procedural and study design elements. Table 2: Incidence ≥2% in One or More Treatment Groups Drug-Related Clinical Adverse Experiences in MTOPS Adverse Experience Placebo (N=737) (%) Doxazosin 4 mg or 8 mg Doxazosin dose was achieved by weekly titration (1 to 2 to 4 to 8 mg). The final tolerated dose (4 mg or 8 mg) was administered at end-Week 4. Only those patients tolerating at least 4 mg were kept on doxazosin. The majority of patients received the 8-mg dose over the duration of the study. (N=756) (%) Finasteride (N=768) (%) Combination (N=786) (%) Body as a whole Asthenia 7.1 15.7 5.3 16.8 Headache 2.3 4.1 2.0 2.3 Cardiovascular Hypotension 0.7 3.4 1.2 1.5 Postural Hypotension 8.0 16.7 9.1 17.8 Metabolic and Nutritional Peripheral Edema 0.9 2.6 1.3 3.3 Nervous Dizziness 8.1 17.7 7.4 23.2 Libido Decreased 5.7 7.0 10.0 11.6 Somnolence 1.5 3.7 1.7 3.1 Respiratory Dyspnea 0.7 2.1 0.7 1.9 Rhinitis 0.5 1.3 1.0 2.4 Urogenital Abnormal Ejaculation 2.3 4.5 7.2 14.1 Gynecomastia 0.7 1.1 2.2 1.5 Impotence 12.2 14.4 18.5 22.6 Sexual Function Abnormal 0.9 2.0 2.5 3.1 Long-Term Data High-Grade Prostate Cancer The PCPT trial was a 7-year randomized, double-blind, placebo-controlled trial that enrolled 18,882 men ≥55 years of age with a normal digital rectal examination and a PSA ≤3.0 ng/mL. Men received either PROSCAR (finasteride 5 mg) or placebo daily. Patients were evaluated annually with PSA and digital rectal exams. Biopsies were performed for elevated PSA, an abnormal digital rectal exam, or the end of study. The incidence of Gleason score 8-10 prostate cancer was higher in men treated with finasteride (1.8%) than in those treated with placebo (1.1%) [see Indications and Usage (1.3) and Warnings and Precautions (5.2) ]. In a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART), similar results for Gleason score 8-10 prostate cancer were observed (1% dutasteride vs 0.5% placebo). No clinical benefit has been demonstrated in patients with prostate cancer treated with PROSCAR. Breast Cancer During the 4- to 6-year placebo- and comparator-controlled MTOPS study that enrolled 3047 men, there were 4 cases of breast cancer in men treated with finasteride but no cases in men not treated with finasteride. During the 4-year, placebo-controlled PLESS study that enrolled 3040 men, there were 2 cases of breast cancer in placebo-treated men but no cases in men treated with finasteride. During the 7-year placebo-controlled Prostate Cancer Prevention Trial (PCPT) that enrolled 18,882 men, there was 1 case of breast cancer in men treated with finasteride, and 1 case of breast cancer in men treated with placebo. The relationship between long-term use of finasteride and male breast neoplasia is currently unknown. Sexual Function There is no evidence of increased sexual adverse experiences with increased duration of treatment with PROSCAR. New reports of drug-related sexual adverse experiences decreased with duration of therapy. 6.2 Postmarketing Experience The following additional adverse events have been reported in postmarketing experience with PROSCAR.

evidence of increased sexual adverse experiences with increased duration of treatment with PROSCAR. New reports of drug-related sexual adverse experiences decreased with duration of therapy. 6.2 Postmarketing Experience The following additional adverse events have been reported in postmarketing experience with PROSCAR. Because these events 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: - hypersensitivity reactions, such as pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face) - testicular pain - hematospermia - sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, decreased libido and ejaculation disorders (e.g. reduced ejaculate volume). These events were reported rarely in men taking PROSCAR for the treatment of BPH. Most men were older and were taking concomitant medications and/or had co-morbid conditions. The independent role of PROSCAR in these events is unknown. - male infertility and/or poor seminal quality were reported rarely in men taking PROSCAR for the treatment of BPH. Normalization or improvement of poor seminal quality has been reported after discontinuation of finasteride. The independent role of PROSCAR in these events is unknown. - depression - suicidal ideation - male breast cancer. The following additional adverse event related to sexual dysfunction that continued after discontinuation of treatment has been reported in postmarketing experience with finasteride at lower doses used to treat male pattern baldness. Because the event is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to drug exposure: - orgasm disorders

<table width="618.000" ID="Table1"><caption>Table 1: Drug-Related Adverse Experiences</caption><col width="22.7%"/><col width="20.9%"/><col width="17.8%"/><col width="21.2%"/><col width="17.4%"/><thead><tr><th align="center" valign="top" styleCode="Toprule Lrule Rrule"/><th align="center" valign="top" colspan="2" styleCode="Botrule Lrule Rrule">Year 1 (%)</th><th align="center" valign="top" colspan="2" styleCode="Botrule Lrule Rrule">Years 2, 3 and 4<footnote ID="id-e6b4235e-8c63-40c4-a09e-78f5556536ad">Combined Years 2-4</footnote> (%)</th></tr><tr><th align="center" valign="top" styleCode="Botrule Lrule Rrule"/><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Finasteride</th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Placebo</th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Finasteride</th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Placebo</th></tr></thead><tfoot><tr><td align="left" valign="top" colspan="5">N = 1524 and 1516, finasteride vs placebo, respectively</td></tr></tfoot><tbody><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Impotence</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">8.1</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">3.7</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">5.1</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">5.1</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Decreased Libido</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">6.4</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">3.4</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">2.6</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">2.6</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Decreased Volume of Ejaculate</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule"> 3.7</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule"> 0.8</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule"> 1.5</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule"> 0.5</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Ejaculation Disorder</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.8</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.1</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.2</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.1</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Breast Enlargement</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.5</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.1</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">1.8</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">1.1</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Breast Tenderness</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.4</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.1</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.7

n="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Breast Tenderness</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.4</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.1</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.7 </td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.3</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Rash</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.5</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.2</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.5</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.1</td></tr></tbody></table> <table width="730.000" ID="Table2"><caption>Table 2: Incidence &#x2265;2% in One or More Treatment Groups Drug-Related Clinical Adverse Experiences in MTOPS</caption><col width="30%"/><col width="15%"/><col width="15%"/><col width="20%"/><col width="20%"/><thead><tr><th align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule">Adverse Experience</th><th align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">Placebo (N=737) (%)</th><th align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">Doxazosin 4 mg or 8 mg<footnote ID="t2f1">Doxazosin dose was achieved by weekly titration (1 to 2 to 4 to 8 mg). The final tolerated dose (4 mg or 8 mg) was administered at end-Week 4. Only those patients tolerating at least 4 mg were kept on doxazosin.

lign="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">Doxazosin 4 mg or 8 mg<footnote ID="t2f1">Doxazosin dose was achieved by weekly titration (1 to 2 to 4 to 8 mg). The final tolerated dose (4 mg or 8 mg) was administered at end-Week 4. Only those patients tolerating at least 4 mg were kept on doxazosin. The majority of patients received the 8-mg dose over the duration of the study.</footnote> (N=756) (%)</th><th align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">Finasteride (N=768) (%)</th><th align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">Combination (N=786) (%)</th></tr></thead><tbody><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule"> Body as a whole</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Toprule Lrule Rrule"> Asthenia</td><td align="center" valign="top" styleCode="Toprule Lrule Rrule">7.1</td><td align="center" valign="top" styleCode="Toprule Lrule Rrule">15.7</td><td align="center" valign="top" styleCode="Toprule Lrule Rrule">5.3</td><td align="center" valign="top" styleCode="Toprule Lrule Rrule">16.8</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Headache</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">2.3</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">4.1</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">2.0</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">2.3</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Cardiovascular</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Hypotension</td><td align="center" valign="top" styleCode="Lrule Rrule">0.7</td><td align="center" valign="top" styleCode="Lrule Rrule">3.4</td><td align="center" valign="top" styleCode="Lrule Rrule">1.2</td><td align="center" valign="top" styleCode="Lrule Rrule">1.5</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Postural Hypotension</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">8.0</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">16.7</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">9.1</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">17.8</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Metabolic and Nutritional</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Peripheral Edema</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">0.9</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">2.6</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">1.3</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">3.3</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Nervous</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lru

Toprule Lrule Rrule">1.3</td><td align="center" valign="top" styleCode="Botrule Toprule Lrule Rrule">3.3</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Nervous</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lru le Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Dizziness</td><td align="center" valign="top" styleCode="Lrule Rrule">8.1</td><td align="center" valign="top" styleCode="Lrule Rrule">17.7</td><td align="center" valign="top" styleCode="Lrule Rrule">7.4</td><td align="center" valign="top" styleCode="Lrule Rrule">23.2</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Libido Decreased</td><td align="center" valign="top" styleCode="Lrule Rrule">5.7</td><td align="center" valign="top" styleCode="Lrule Rrule">7.0</td><td align="center" valign="top" styleCode="Lrule Rrule">10.0</td><td align="center" valign="top" styleCode="Lrule Rrule">11.6</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Somnolence</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">1.5</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">3.7</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">1.7</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">3.1</td></tr><tr><td align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"> Respiratory</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Dyspnea</td><td align="center" valign="top" styleCode="Lrule Rrule">0.7</td><td align="center" valign="top" styleCode="Lrule Rrule">2.1</td><td align="center" valign="top" styleCode="Lrule Rrule">0.7</td><td align="center" valign="top" styleCode="Lrule Rrule">1.9</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Rhinitis</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.5</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">1.3</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">1.0</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">2.4</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Urogenital</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Abnormal Ejaculation</td><td align="center" valign="top" styleCode="Lrule Rrule">2.3</td><td align="center" valign="top" styleCode="Lrule Rrule">4.5</td><td align="center" valign="top" styleCode="Lrule Rrule">7.2</td><td align="center" valign="top" styleCode="Lrule Rrule">14.1</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Gynecomastia</td><td align="center" valign="top" styleCode="Lrule Rrule">0.7</td><td align="center" valign="top" styleCode="Lrule Rrule">1.1</td><td align="center" valign="top" styleCode="Lrule Rrule">2.2</td><td align="center" valign="top" styleCode="Lrule Rrule">1.5</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Impotence</td><td align="center" valign="top" styleCode="Lrule Rrule">12.2</td><td align="center" valign="top" styleCode="Lrule Rrule">14.4</td><td al

ign="top" styleCode="Lrule Rrule">2.2</td><td align="center" valign="top" styleCode="Lrule Rrule">1.5</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Impotence</td><td align="center" valign="top" styleCode="Lrule Rrule">12.2</td><td align="center" valign="top" styleCode="Lrule Rrule">14.4</td><td al ign="center" valign="top" styleCode="Lrule Rrule">18.5</td><td align="center" valign="top" styleCode="Lrule Rrule">22.6</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Sexual Function Abnormal</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.9</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">2.0</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">2.5</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">3.1</td></tr></tbody></table>

7 DRUG INTERACTIONS 7.1 Cytochrome P450-Linked Drug Metabolizing Enzyme System No drug interactions of clinical importance have been identified. Finasteride does not appear to affect the cytochrome P450-linked drug metabolizing enzyme system. Compounds that have been tested in man have included antipyrine, digoxin, propranolol, theophylline, and warfarin and no clinically meaningful interactions were found. 7.2 Other Concomitant Therapy Although specific interaction studies were not performed, PROSCAR was concomitantly used in clinical studies with acetaminophen, acetylsalicylic acid, α-blockers, angiotensin-converting enzyme (ACE) inhibitors, analgesics, anti-convulsants, beta-adrenergic blocking agents, diuretics, calcium channel blockers, cardiac nitrates, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, H 2 antagonists and quinolone anti-infectives without evidence of clinically significant adverse interactions.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary PROSCAR is contraindicated in pregnant females and not indicated for use in females. Based on animal studies and the mechanism of action, PROSCAR may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.1) ]. In an embryo-fetal development study in rats, there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring of pregnant rats administered oral finasteride during the period of major organogenesis at doses approximately 0.1 to 86 times the maximum recommended human dose (MRHD) of 5 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day). Decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development were also observed in male offspring at oral maternal doses approximately 0.03 times the MRHD (based on AUC at animal dose of 0.03 mg/kg/day), along with decreased anogenital distance in male offspring at oral maternal doses approximately 0.003 times the MRHD (based on AUC at animal dose of 0.003 mg/kg/day). PROSCAR is a Type II 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. 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 the male fetus. Abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (DHT) is inhibited by 5α-reductase inhibitors. These outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. Females could be exposed to finasteride through contact with crushed or broken PROSCAR tablets or semen from a male partner taking PROSCAR. With regard to finasteride exposure through the skin, PROSCAR tablets are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. Females who are pregnant or may potentially be pregnant should not handle crushed or broken PROSCAR tablets because of possible exposure of a male fetus. With regard to potential finasteride exposure through semen, three studies have been conducted that measured finasteride concentrations in semen in men receiving PROSCAR 5 mg/day. In these studies the highest amount of finasteride in semen was estimated to be 50- to 100-fold less than the dose of finasteride (5 μg) that had no effect on circulating DHT levels in men [see Data and Clinical Pharmacology (12.3) ]. Data Human Data In 2 studies of healthy subjects (n=69) receiving PROSCAR 5 mg/day for 6-24 weeks, finasteride concentrations in semen ranged from undetectable (<0.1 ng/mL) to 10.54 ng/mL. In an earlier study using a less sensitive assay, finasteride concentrations in semen of 16 subjects receiving PROSCAR 5 mg/day ranged from undetectable (<1.0 ng/mL) to 21 ng/mL. Using the highest semen level measured and assuming 100% absorption would be up to 105 ng per day, which is 50- to 100-fold less than the dose of finasteride (5 μg) that had no effect on circulating DHT levels in men [see Clinical Pharmacology (12.3) ] . Animal Data In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17).

ng per day, which is 50- to 100-fold less than the dose of finasteride (5 μg) that had no effect on circulating DHT levels in men [see Clinical Pharmacology (12.3) ] . Animal Data In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). At maternal doses of oral finasteride approximately 0.1 to 86 times the maximum recommended human dose (MRHD) of 5 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. Exposure multiples were estimated using data from nonpregnant rats. Days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia. At oral maternal doses approximately 0.03 times the MRHD (based on AUC at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. Decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.003 times the MRHD (based on AUC at animal dose of 0.003 mg/kg/day). No abnormalities were observed in female offspring at any maternal dose of finasteride. No developmental abnormalities were observed in the offspring of untreated females mated with finasteride treated male rats that received approximately 61 times the MRHD (based on AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 3 times the MRHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. No effects on fertility were seen in female offspring under these conditions. No evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6-18) at maternal oral doses up to 100 mg/kg/day, (finasteride exposure levels were not measured in rabbits). However, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. The fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20-100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. Intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/mL or about 143 times the highest estimated exposure of pregnant females to finasteride from semen of men taking 5 mg/day) resulted in no abnormalities in male fetuses. In confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 18,000 times the highest estimated blood levels of finasteride from semen of men taking 5 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. No other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose. 8.2 Lactation Risk Summary PROSCAR is not indicated for use in females. 8.3 Females and Males of Reproductive Potential Infertility Females PROSCAR is not indicated for use in females. Males Treatment with PROSCAR for 24 weeks to evaluate semen parameters in healthy male volunteers revealed no clinically meaningful effects on sperm concentration, mobility, morphology, or pH. A 0.6 mL (22.1%) median decrease in ejaculate volume with a concomitant reduction in total sperm per ejaculate was observed.

s. Males Treatment with PROSCAR for 24 weeks to evaluate semen parameters in healthy male volunteers revealed no clinically meaningful effects on sperm concentration, mobility, morphology, or pH. A 0.6 mL (22.1%) median decrease in ejaculate volume with a concomitant reduction in total sperm per ejaculate was observed. These parameters remained within the normal range and were reversible upon discontinuation of therapy with an average time to return to baseline of 84 weeks [see Warnings and Precautions (5.5) ]. There have been postmarketing reports of male infertility and/or poor seminal quality; normalization or improvement of seminal quality has been reported after discontinuation of finasteride [see Adverse Reactions (6.2) ]. 8.4 Pediatric Use PROSCAR is not indicated for use in pediatric patients. Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of subjects included in PLESS, 1480 and 105 subjects were 65 and over and 75 and over, respectively. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. No dosage adjustment is necessary in the elderly [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] . 8.6 Hepatic Impairment Caution should be exercised in the administration of PROSCAR in those patients with liver function abnormalities, as finasteride is metabolized extensively in the liver [see Clinical Pharmacology (12.3) ]. 8.7 Renal Impairment No dosage adjustment is necessary in patients with renal impairment [see Clinical Pharmacology (12.3) ] .

8.1 Pregnancy Risk Summary PROSCAR is contraindicated in pregnant females and not indicated for use in females. Based on animal studies and the mechanism of action, PROSCAR may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.1) ]. In an embryo-fetal development study in rats, there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring of pregnant rats administered oral finasteride during the period of major organogenesis at doses approximately 0.1 to 86 times the maximum recommended human dose (MRHD) of 5 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day). Decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development were also observed in male offspring at oral maternal doses approximately 0.03 times the MRHD (based on AUC at animal dose of 0.03 mg/kg/day), along with decreased anogenital distance in male offspring at oral maternal doses approximately 0.003 times the MRHD (based on AUC at animal dose of 0.003 mg/kg/day). PROSCAR is a Type II 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. 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 the male fetus. Abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (DHT) is inhibited by 5α-reductase inhibitors. These outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. Females could be exposed to finasteride through contact with crushed or broken PROSCAR tablets or semen from a male partner taking PROSCAR. With regard to finasteride exposure through the skin, PROSCAR tablets are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. Females who are pregnant or may potentially be pregnant should not handle crushed or broken PROSCAR tablets because of possible exposure of a male fetus. With regard to potential finasteride exposure through semen, three studies have been conducted that measured finasteride concentrations in semen in men receiving PROSCAR 5 mg/day. In these studies the highest amount of finasteride in semen was estimated to be 50- to 100-fold less than the dose of finasteride (5 μg) that had no effect on circulating DHT levels in men [see Data and Clinical Pharmacology (12.3) ]. Data Human Data In 2 studies of healthy subjects (n=69) receiving PROSCAR 5 mg/day for 6-24 weeks, finasteride concentrations in semen ranged from undetectable (<0.1 ng/mL) to 10.54 ng/mL. In an earlier study using a less sensitive assay, finasteride concentrations in semen of 16 subjects receiving PROSCAR 5 mg/day ranged from undetectable (<1.0 ng/mL) to 21 ng/mL. Using the highest semen level measured and assuming 100% absorption would be up to 105 ng per day, which is 50- to 100-fold less than the dose of finasteride (5 μg) that had no effect on circulating DHT levels in men [see Clinical Pharmacology (12.3) ] . Animal Data In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17).

ng per day, which is 50- to 100-fold less than the dose of finasteride (5 μg) that had no effect on circulating DHT levels in men [see Clinical Pharmacology (12.3) ] . Animal Data In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). At maternal doses of oral finasteride approximately 0.1 to 86 times the maximum recommended human dose (MRHD) of 5 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. Exposure multiples were estimated using data from nonpregnant rats. Days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia. At oral maternal doses approximately 0.03 times the MRHD (based on AUC at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. Decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.003 times the MRHD (based on AUC at animal dose of 0.003 mg/kg/day). No abnormalities were observed in female offspring at any maternal dose of finasteride. No developmental abnormalities were observed in the offspring of untreated females mated with finasteride treated male rats that received approximately 61 times the MRHD (based on AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 3 times the MRHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. No effects on fertility were seen in female offspring under these conditions. No evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6-18) at maternal oral doses up to 100 mg/kg/day, (finasteride exposure levels were not measured in rabbits). However, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. The fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20-100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. Intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/mL or about 143 times the highest estimated exposure of pregnant females to finasteride from semen of men taking 5 mg/day) resulted in no abnormalities in male fetuses. In confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 18,000 times the highest estimated blood levels of finasteride from semen of men taking 5 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. No other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose.

8.5 Geriatric Use Of the total number of subjects included in PLESS, 1480 and 105 subjects were 65 and over and 75 and over, respectively. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. No dosage adjustment is necessary in the elderly [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] .

10 OVERDOSAGE Patients have received single doses of PROSCAR up to 400 mg and multiple doses of PROSCAR up to 80 mg/day for three months without adverse effects. Until further experience is obtained, no specific treatment for an overdose with PROSCAR can be recommended. Significant lethality was observed in male and female mice at single oral doses of 1500 mg/m 2 (500 mg/kg) and in female and male rats at single oral doses of 2360 mg/m 2 (400 mg/kg) and 5900 mg/m 2 (1000 mg/kg), respectively.

11 DESCRIPTION PROSCAR (finasteride), a synthetic 4-azasteroid compound, is a specific inhibitor of steroid Type II 5α-reductase, an intracellular enzyme that converts the androgen testosterone into 5α-dihydrotestosterone (DHT). Finasteride is 4-azaandrost-1-ene-17-carboxamide, N-(1,1-dimethylethyl)-3-oxo-,(5α,17ß)-. The empirical formula of finasteride is C 23 H 36 N 2 O 2 and its molecular weight is 372.55. Its structural formula is: Finasteride is a white crystalline powder with a melting point near 250°C. It is freely soluble in chloroform and in lower alcohol solvents, but is practically insoluble in water. PROSCAR (finasteride) tablets for oral administration are film-coated tablets that contain 5 mg of finasteride and the following inactive ingredients: hydrous lactose, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, hydroxypropyl cellulose LF, hydroxypropyl methylcellulose, titanium dioxide, magnesium stearate, talc, docusate sodium, FD&C Blue 2 aluminum lake and yellow iron oxide. image of finasteride chemical structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The development and enlargement of the prostate gland is dependent on the potent androgen, 5α-dihydrotestosterone (DHT). Type II 5α-reductase metabolizes testosterone to DHT in the prostate gland, liver and skin. DHT induces androgenic effects by binding to androgen receptors in the cell nuclei of these organs. Finasteride is a competitive and specific inhibitor of Type II 5α-reductase with which it slowly forms a stable enzyme complex. Turnover from this complex is extremely slow (t ½ ~ 30 days). This has been demonstrated both in vivo and in vitro . Finasteride has no affinity for the androgen receptor. In man, the 5α-reduced steroid metabolites in blood and urine are decreased after administration of finasteride. 12.2 Pharmacodynamics In man, a single 5-mg oral dose of PROSCAR produces a rapid reduction in serum DHT concentration, with the maximum effect observed 8 hours after the first dose. The suppression of DHT is maintained throughout the 24-hour dosing interval and with continued treatment. Daily dosing of PROSCAR at 5 mg/day for up to 4 years has been shown to reduce the serum DHT concentration by approximately 70%. The median circulating level of testosterone increased by approximately 10-20% but remained within the physiologic range. In a separate study in healthy men treated with finasteride 1 mg per day (n=82) or placebo (n=69), mean circulating levels of testosterone and estradiol were increased by approximately 15% as compared to baseline, but these remained within the physiologic range. In patients receiving PROSCAR 5 mg/day, increases of about 10% were observed in luteinizing hormone (LH) and follicle-stimulating hormone (FSH), but levels remained within the normal range. In healthy volunteers, treatment with PROSCAR did not alter the response of LH and FSH to gonadotropin-releasing hormone indicating that the hypothalamic-pituitary-testicular axis was not affected. In patients with BPH, PROSCAR has no effect on circulating levels of cortisol, prolactin, thyroid-stimulating hormone, or thyroxine. No clinically meaningful effect was observed on the plasma lipid profile (i.e., total cholesterol, low density lipoproteins, high density lipoproteins and triglycerides) or bone mineral density. Adult males with genetically inherited Type II 5α-reductase deficiency also have decreased levels of DHT. Except for the associated urogenital defects present at birth, no other clinical abnormalities related to Type II 5α-reductase deficiency have been observed in these individuals. These individuals have a small prostate gland throughout life and do not develop BPH. In patients with BPH treated with finasteride (1-100 mg/day) for 7-10 days prior to prostatectomy, an approximate 80% lower DHT content was measured in prostatic tissue removed at surgery, compared to placebo; testosterone tissue concentration was increased up to 10 times over pretreatment levels, relative to placebo. Intraprostatic content of PSA was also decreased. In healthy male volunteers treated with PROSCAR for 14 days, discontinuation of therapy resulted in a return of DHT levels to pretreatment levels in approximately 2 weeks. In patients treated for three months, prostate volume, which declined by approximately 20%, returned to close to baseline value after approximately three months of discontinuation of therapy.

SCAR for 14 days, discontinuation of therapy resulted in a return of DHT levels to pretreatment levels in approximately 2 weeks. In patients treated for three months, prostate volume, which declined by approximately 20%, returned to close to baseline value after approximately three months of discontinuation of therapy. 12.3 Pharmacokinetics Absorption In a study of 15 healthy young subjects, the mean bioavailability of finasteride 5-mg tablets was 63% (range 34-108%), based on the ratio of area under the curve (AUC) relative to an intravenous (IV) reference dose. Maximum finasteride plasma concentration averaged 37 ng/mL (range, 27-49 ng/mL) and was reached 1-2 hours postdose. Bioavailability of finasteride was not affected by food. Distribution Mean steady-state volume of distribution was 76 liters (range, 44-96 liters). Approximately 90% of circulating finasteride is bound to plasma proteins. There is a slow accumulation phase for finasteride after multiple dosing. After dosing with 5 mg/day of finasteride for 17 days, plasma concentrations of finasteride were 47 and 54% higher than after the first dose in men 45-60 years old (n=12) and ≥70 years old (n=12), respectively. Mean trough concentrations after 17 days of dosing were 6.2 ng/mL (range, 2.4-9.8 ng/mL) and 8.1 ng/mL (range, 1.8-19.7 ng/mL), respectively, in the two age groups. Although steady state was not reached in this study, mean trough plasma concentration in another study in patients with BPH (mean age, 65 years) receiving 5 mg/day was 9.4 ng/mL (range, 7.1-13.3 ng/mL; n=22) after over a year of dosing. Finasteride has been shown to cross the blood brain barrier but does not appear to distribute preferentially to the CSF. In 2 studies of healthy subjects (n=69) receiving PROSCAR 5 mg/day for 6-24 weeks, finasteride concentrations in semen ranged from undetectable (<0.1 ng/mL) to 10.54 ng/mL. In an earlier study using a less sensitive assay, finasteride concentrations in the semen of 16 subjects receiving PROSCAR 5 mg/day ranged from undetectable (<1.0 ng/mL) to 21 ng/mL. Thus, based on a 5-mL ejaculate volume, the amount of finasteride in semen was estimated to be 50- to 100-fold less than the dose of finasteride (5 μg) that had no effect on circulating DHT levels in men [see also Use in Specific Populations (8.1) ] . Metabolism Finasteride is extensively metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme subfamily. Two metabolites, the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites, have been identified that possess no more than 20% of the 5α-reductase inhibitory activity of finasteride. Excretion In healthy young subjects (n=15), mean plasma clearance of finasteride was 165 mL/min (range, 70-279 mL/min) and mean elimination half-life in plasma was 6 hours (range, 3-16 hours). Following an oral dose of 14 C-finasteride in man (n=6), a mean of 39% (range, 32-46%) of the dose was excreted in the urine in the form of metabolites; 57% (range, 51-64%) was excreted in the feces. The mean terminal half-life of finasteride in subjects ≥70 years of age was approximately 8 hours (range, 6-15 hours; n=12), compared with 6 hours (range, 4-12 hours; n=12) in subjects 45-60 years of age. As a result, mean AUC (0-24 hr) after 17 days of dosing was 15% higher in subjects ≥70 years of age than in subjects 45-60 years of age (p=0.02). Table 3: Mean (SD) Pharmacokinetic Parameters in Healthy Young Subjects (n=15) Mean (± SD) Bioavailability 63% (34-108%) Range Clearance (mL/min) 165 (55) Volume of Distribution (L) 76 (14) Half-Life (hours) 6.2 (2.1) Pediatric Finasteride pharmacokinetics have not been investigated in patients <18 years of age.

0.02). Table 3: Mean (SD) Pharmacokinetic Parameters in Healthy Young Subjects (n=15) Mean (± SD) Bioavailability 63% (34-108%) Range Clearance (mL/min) 165 (55) Volume of Distribution (L) 76 (14) Half-Life (hours) 6.2 (2.1) Pediatric Finasteride pharmacokinetics have not been investigated in patients <18 years of age. Finasteride is not indicated for use in pediatric patients [see Warnings and Precautions (5.4) , Use in Specific Populations (8.4) ]. Gender Finasteride is not indicated for use in females [see Contraindications (4) , Warnings and Precautions (5.3 and 5.4 ), Use in Specific Populations (8.1) , and How Supplied/Storage and Handling (16) ] . Geriatric No dosage adjustment is necessary in the elderly. Although the elimination rate of finasteride is decreased in the elderly, these findings are of no clinical significance. [See Clinical Pharmacology (12.3) and Use in Specific Populations (8.5) .] Table 4: Mean (SD) Noncompartmental Pharmacokinetic Parameters After Multiple Doses of 5 mg/day in Older Men Mean (± SD) 45-60 years old (n=12) ≥70 years old (n=12) AUC (ng•hr/mL) 389 (98) 463 (186) Peak Concentration (ng/mL) 46.2 (8.7) 48.4 (14.7) Time to Peak (hours) 1.8 (0.7) 1.8 (0.6) Half-Life (hours) First-dose values; all other parameters are last-dose values 6.0 (1.5) 8.2 (2.5) Race The effect of race on finasteride pharmacokinetics has not been studied. Hepatic Impairment The effect of hepatic impairment on finasteride pharmacokinetics has not been studied. Caution should be exercised in the administration of PROSCAR in those patients with liver function abnormalities, as finasteride is metabolized extensively in the liver. Renal Impairment No dosage adjustment is necessary in patients with renal impairment. In patients with chronic renal impairment, with creatinine clearances ranging from 9.0 to 55 mL/min, AUC, maximum plasma concentration, half-life, and protein binding after a single dose of 14 C-finasteride were similar to values obtained in healthy volunteers. Urinary excretion of metabolites was decreased in patients with renal impairment. This decrease was associated with an increase in fecal excretion of metabolites. Plasma concentrations of metabolites were significantly higher in patients with renal impairment (based on a 60% increase in total radioactivity AUC). However, finasteride has been well tolerated in BPH patients with normal renal function receiving up to 80 mg/day for 12 weeks, where exposure of these patients to metabolites would presumably be much greater.

12.1 Mechanism of Action The development and enlargement of the prostate gland is dependent on the potent androgen, 5α-dihydrotestosterone (DHT). Type II 5α-reductase metabolizes testosterone to DHT in the prostate gland, liver and skin. DHT induces androgenic effects by binding to androgen receptors in the cell nuclei of these organs. Finasteride is a competitive and specific inhibitor of Type II 5α-reductase with which it slowly forms a stable enzyme complex. Turnover from this complex is extremely slow (t ½ ~ 30 days). This has been demonstrated both in vivo and in vitro . Finasteride has no affinity for the androgen receptor. In man, the 5α-reduced steroid metabolites in blood and urine are decreased after administration of finasteride.

12.2 Pharmacodynamics In man, a single 5-mg oral dose of PROSCAR produces a rapid reduction in serum DHT concentration, with the maximum effect observed 8 hours after the first dose. The suppression of DHT is maintained throughout the 24-hour dosing interval and with continued treatment. Daily dosing of PROSCAR at 5 mg/day for up to 4 years has been shown to reduce the serum DHT concentration by approximately 70%. The median circulating level of testosterone increased by approximately 10-20% but remained within the physiologic range. In a separate study in healthy men treated with finasteride 1 mg per day (n=82) or placebo (n=69), mean circulating levels of testosterone and estradiol were increased by approximately 15% as compared to baseline, but these remained within the physiologic range. In patients receiving PROSCAR 5 mg/day, increases of about 10% were observed in luteinizing hormone (LH) and follicle-stimulating hormone (FSH), but levels remained within the normal range. In healthy volunteers, treatment with PROSCAR did not alter the response of LH and FSH to gonadotropin-releasing hormone indicating that the hypothalamic-pituitary-testicular axis was not affected. In patients with BPH, PROSCAR has no effect on circulating levels of cortisol, prolactin, thyroid-stimulating hormone, or thyroxine. No clinically meaningful effect was observed on the plasma lipid profile (i.e., total cholesterol, low density lipoproteins, high density lipoproteins and triglycerides) or bone mineral density. Adult males with genetically inherited Type II 5α-reductase deficiency also have decreased levels of DHT. Except for the associated urogenital defects present at birth, no other clinical abnormalities related to Type II 5α-reductase deficiency have been observed in these individuals. These individuals have a small prostate gland throughout life and do not develop BPH. In patients with BPH treated with finasteride (1-100 mg/day) for 7-10 days prior to prostatectomy, an approximate 80% lower DHT content was measured in prostatic tissue removed at surgery, compared to placebo; testosterone tissue concentration was increased up to 10 times over pretreatment levels, relative to placebo. Intraprostatic content of PSA was also decreased. In healthy male volunteers treated with PROSCAR for 14 days, discontinuation of therapy resulted in a return of DHT levels to pretreatment levels in approximately 2 weeks. In patients treated for three months, prostate volume, which declined by approximately 20%, returned to close to baseline value after approximately three months of discontinuation of therapy.

12.3 Pharmacokinetics Absorption In a study of 15 healthy young subjects, the mean bioavailability of finasteride 5-mg tablets was 63% (range 34-108%), based on the ratio of area under the curve (AUC) relative to an intravenous (IV) reference dose. Maximum finasteride plasma concentration averaged 37 ng/mL (range, 27-49 ng/mL) and was reached 1-2 hours postdose. Bioavailability of finasteride was not affected by food. Distribution Mean steady-state volume of distribution was 76 liters (range, 44-96 liters). Approximately 90% of circulating finasteride is bound to plasma proteins. There is a slow accumulation phase for finasteride after multiple dosing. After dosing with 5 mg/day of finasteride for 17 days, plasma concentrations of finasteride were 47 and 54% higher than after the first dose in men 45-60 years old (n=12) and ≥70 years old (n=12), respectively. Mean trough concentrations after 17 days of dosing were 6.2 ng/mL (range, 2.4-9.8 ng/mL) and 8.1 ng/mL (range, 1.8-19.7 ng/mL), respectively, in the two age groups. Although steady state was not reached in this study, mean trough plasma concentration in another study in patients with BPH (mean age, 65 years) receiving 5 mg/day was 9.4 ng/mL (range, 7.1-13.3 ng/mL; n=22) after over a year of dosing. Finasteride has been shown to cross the blood brain barrier but does not appear to distribute preferentially to the CSF. In 2 studies of healthy subjects (n=69) receiving PROSCAR 5 mg/day for 6-24 weeks, finasteride concentrations in semen ranged from undetectable (<0.1 ng/mL) to 10.54 ng/mL. In an earlier study using a less sensitive assay, finasteride concentrations in the semen of 16 subjects receiving PROSCAR 5 mg/day ranged from undetectable (<1.0 ng/mL) to 21 ng/mL. Thus, based on a 5-mL ejaculate volume, the amount of finasteride in semen was estimated to be 50- to 100-fold less than the dose of finasteride (5 μg) that had no effect on circulating DHT levels in men [see also Use in Specific Populations (8.1) ] . Metabolism Finasteride is extensively metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme subfamily. Two metabolites, the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites, have been identified that possess no more than 20% of the 5α-reductase inhibitory activity of finasteride. Excretion In healthy young subjects (n=15), mean plasma clearance of finasteride was 165 mL/min (range, 70-279 mL/min) and mean elimination half-life in plasma was 6 hours (range, 3-16 hours). Following an oral dose of 14 C-finasteride in man (n=6), a mean of 39% (range, 32-46%) of the dose was excreted in the urine in the form of metabolites; 57% (range, 51-64%) was excreted in the feces. The mean terminal half-life of finasteride in subjects ≥70 years of age was approximately 8 hours (range, 6-15 hours; n=12), compared with 6 hours (range, 4-12 hours; n=12) in subjects 45-60 years of age. As a result, mean AUC (0-24 hr) after 17 days of dosing was 15% higher in subjects ≥70 years of age than in subjects 45-60 years of age (p=0.02). Table 3: Mean (SD) Pharmacokinetic Parameters in Healthy Young Subjects (n=15) Mean (± SD) Bioavailability 63% (34-108%) Range Clearance (mL/min) 165 (55) Volume of Distribution (L) 76 (14) Half-Life (hours) 6.2 (2.1) Pediatric Finasteride pharmacokinetics have not been investigated in patients <18 years of age.

<table width="385.000" ID="Table3"><caption>Table 3: Mean (SD) Pharmacokinetic Parameters in Healthy Young Subjects (n=15)</caption><col width="51.4%"/><col width="48.6%"/><thead><tr><th align="left" valign="top" styleCode="Botrule Lrule Rrule"> </th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Mean (&#xB1; SD)</th></tr></thead><tbody><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Bioavailability</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">63% (34-108%)<footnote ID="t3f1">Range</footnote></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Clearance (mL/min)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">165 (55)</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Volume of Distribution (L)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">76 (14)</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Half-Life (hours)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">6.2 (2.1)</td></tr></tbody></table>

trule Lrule Rrule"> Volume of Distribution (L)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">76 (14)</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Half-Life (hours)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">6.2 (2.1)</td></tr></tbody></table> <table width="500.000" ID="Table4"><caption>Table 4: Mean (SD) Noncompartmental Pharmacokinetic Parameters After Multiple Doses of 5 mg/day in Older Men</caption><col width="42.8%"/><col width="29.8%"/><col width="27.4%"/><thead><tr><th align="left" valign="top" styleCode="Lrule Rrule"/><th align="center" valign="top" colspan="2" styleCode="Botrule Lrule Rrule">Mean (&#xB1; SD)</th></tr><tr><th align="left" valign="top" styleCode="Botrule Lrule Rrule"/><th align="center" valign="top" styleCode="Botrule Lrule Rrule">45-60 years old (n=12)</th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">&#x2265;70 years old (n=12)</th></tr></thead><tbody><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> AUC (ng&#x2022;hr/mL)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">389 (98)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">463 (186)</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Peak Concentration (ng/mL)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">46.2 (8.7)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">48.4 (14.7)</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Time to Peak (hours)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">1.8 (0.7)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">1.8 (0.6)</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Half-Life (hours)<footnote ID="t4f1">First-dose values; all other parameters are last-dose values</footnote></td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">6.0 (1.5)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">8.2 (2.5)</td></tr></tbody></table>

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No evidence of a tumorigenic effect was observed in a 24-month study in Sprague-Dawley rats receiving doses of finasteride up to 160 mg/kg/day in males and 320 mg/kg/day in females. These doses produced respective systemic exposure in rats of 111 and 274 times those observed in man receiving the recommended human dose of 5 mg/day. All exposure calculations were based on calculated AUC (0 -24 hr) for animals and mean AUC (0 -24 hr) for man (0.4 μg•hr/mL). In a 19-month carcinogenicity study in CD-1 mice, a statistically significant (p≤0.05) increase in the incidence of testicular Leydig cell adenomas was observed at 228 times the human exposure (250 mg/kg/day). In mice at 23 times the human exposure, estimated (25 mg/kg/day) and in rats at 39 times the human exposure (40 mg/kg/day) an increase in the incidence of Leydig cell hyperplasia was observed. A positive correlation between the proliferative changes in the Leydig cells and an increase in serum LH levels (2- to 3-fold above control) has been demonstrated in both rodent species treated with high doses of finasteride. No drug-related Leydig cell changes were seen in either rats or dogs treated with finasteride for 1 year at 30 and 350 times (20 mg/kg/day and 45 mg/kg/day, respectively) or in mice treated for 19 months at 2.3 times the human exposure, estimated (2.5 mg/kg/day). Mutagenesis No evidence of mutagenicity was observed in an in vitro bacterial mutagenesis assay, a mammalian cell mutagenesis assay, or in an in vitro alkaline elution assay. In an in vitro chromosome aberration assay, using Chinese hamster ovary cells, there was a slight increase in chromosome aberrations. These concentrations correspond to 4000-5000 times the peak plasma levels in man given a total dose of 5 mg. In an in vivo chromosome aberration assay in mice, no treatment-related increase in chromosome aberration was observed with finasteride at the maximum tolerated dose of 250 mg/kg/day (228 times the human exposure) as determined in the carcinogenicity studies. Impairment of Fertility In sexually mature male rabbits treated with finasteride at 543 times the human exposure (80 mg/kg/day) for up to 12 weeks, no effect on fertility, sperm count, or ejaculate volume was seen. In sexually mature male rats treated with 61 times the human exposure (80 mg/kg/day), there were no significant effects on fertility after 6 or 12 weeks of treatment; however, when treatment was continued for up to 24 or 30 weeks, there was an apparent decrease in fertility, fecundity and an associated significant decrease in the weights of the seminal vesicles and prostate. All these effects were reversible within 6 weeks of discontinuation of treatment. No drug-related effect on testes or on mating performance has been seen in rats or rabbits. This decrease in fertility in finasteride-treated rats is secondary to its effect on accessory sex organs (prostate and seminal vesicles) resulting in failure to form a seminal plug. The seminal plug is essential for normal fertility in rats and is not relevant in man.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No evidence of a tumorigenic effect was observed in a 24-month study in Sprague-Dawley rats receiving doses of finasteride up to 160 mg/kg/day in males and 320 mg/kg/day in females. These doses produced respective systemic exposure in rats of 111 and 274 times those observed in man receiving the recommended human dose of 5 mg/day. All exposure calculations were based on calculated AUC (0 -24 hr) for animals and mean AUC (0 -24 hr) for man (0.4 μg•hr/mL). In a 19-month carcinogenicity study in CD-1 mice, a statistically significant (p≤0.05) increase in the incidence of testicular Leydig cell adenomas was observed at 228 times the human exposure (250 mg/kg/day). In mice at 23 times the human exposure, estimated (25 mg/kg/day) and in rats at 39 times the human exposure (40 mg/kg/day) an increase in the incidence of Leydig cell hyperplasia was observed. A positive correlation between the proliferative changes in the Leydig cells and an increase in serum LH levels (2- to 3-fold above control) has been demonstrated in both rodent species treated with high doses of finasteride. No drug-related Leydig cell changes were seen in either rats or dogs treated with finasteride for 1 year at 30 and 350 times (20 mg/kg/day and 45 mg/kg/day, respectively) or in mice treated for 19 months at 2.3 times the human exposure, estimated (2.5 mg/kg/day). Mutagenesis No evidence of mutagenicity was observed in an in vitro bacterial mutagenesis assay, a mammalian cell mutagenesis assay, or in an in vitro alkaline elution assay. In an in vitro chromosome aberration assay, using Chinese hamster ovary cells, there was a slight increase in chromosome aberrations. These concentrations correspond to 4000-5000 times the peak plasma levels in man given a total dose of 5 mg. In an in vivo chromosome aberration assay in mice, no treatment-related increase in chromosome aberration was observed with finasteride at the maximum tolerated dose of 250 mg/kg/day (228 times the human exposure) as determined in the carcinogenicity studies. Impairment of Fertility In sexually mature male rabbits treated with finasteride at 543 times the human exposure (80 mg/kg/day) for up to 12 weeks, no effect on fertility, sperm count, or ejaculate volume was seen. In sexually mature male rats treated with 61 times the human exposure (80 mg/kg/day), there were no significant effects on fertility after 6 or 12 weeks of treatment; however, when treatment was continued for up to 24 or 30 weeks, there was an apparent decrease in fertility, fecundity and an associated significant decrease in the weights of the seminal vesicles and prostate. All these effects were reversible within 6 weeks of discontinuation of treatment. No drug-related effect on testes or on mating performance has been seen in rats or rabbits. This decrease in fertility in finasteride-treated rats is secondary to its effect on accessory sex organs (prostate and seminal vesicles) resulting in failure to form a seminal plug. The seminal plug is essential for normal fertility in rats and is not relevant in man.

14 CLINICAL STUDIES 14.1 Monotherapy PROSCAR 5 mg/day was initially evaluated in patients with symptoms of BPH and enlarged prostates by digital rectal examination in two 1-year, placebo-controlled, randomized, double-blind studies and their 5-year open extensions. PROSCAR was further evaluated in the PROSCAR Long-Term Efficacy and Safety Study (PLESS), a double-blind, randomized, placebo-controlled, 4-year, multicenter study. 3040 patients between the ages of 45 and 78, with moderate to severe symptoms of BPH and an enlarged prostate upon digital rectal examination, were randomized into the study (1524 to finasteride, 1516 to placebo) and 3016 patients were evaluable for efficacy. 1883 patients completed the 4-year study (1000 in the finasteride group, 883 in the placebo group). Effect on Symptom Score Symptoms were quantified using a score similar to the American Urological Association Symptom Score, which evaluated both obstructive symptoms (impairment of size and force of stream, sensation of incomplete bladder emptying, delayed or interrupted urination) and irritative symptoms (nocturia, daytime frequency, need to strain or push the flow of urine) by rating on a 0 to 5 scale for six symptoms and a 0 to 4 scale for one symptom, for a total possible score of 34. Patients in PLESS had moderate to severe symptoms at baseline (mean of approximately 15 points on a 0-34 point scale). Patients randomized to PROSCAR who remained on therapy for 4 years had a mean (± 1 SD) decrease in symptom score of 3.3 (± 5.8) points compared with 1.3 (± 5.6) points in the placebo group. (See Figure 1 .) A statistically significant improvement in symptom score was evident at 1 year in patients treated with PROSCAR vs placebo (–2.3 vs –1.6), and this improvement continued through Year 4. Figure 1 Symptom Score in PLESS Results seen in earlier studies were comparable to those seen in PLESS. Although an early improvement in urinary symptoms was seen in some patients, a therapeutic trial of at least 6 months was generally necessary to assess whether a beneficial response in symptom relief had been achieved. The improvement in BPH symptoms was seen during the first year and maintained throughout an additional 5 years of open extension studies. Effect on Acute Urinary Retention and the Need for Surgery In PLESS, efficacy was also assessed by evaluating treatment failures. Treatment failure was prospectively defined as BPH-related urological events or clinical deterioration, lack of improvement and/or the need for alternative therapy. BPH-related urological events were defined as urological surgical intervention and acute urinary retention requiring catheterization. Complete event information was available for 92% of the patients. The following table ( Table 5 ) summarizes the results.

on, lack of improvement and/or the need for alternative therapy. BPH-related urological events were defined as urological surgical intervention and acute urinary retention requiring catheterization. Complete event information was available for 92% of the patients. The following table ( Table 5 ) summarizes the results. Table 5: All Treatment Failures in PLESS Patients (%) patients with multiple events may be counted more than once for each type of event Event Placebo N=1503 Finasteride N=1513 Relative Risk Hazard ratio based on log rank test 95% CI P Value All Treatment Failures 37.1 26.2 0.68 (0.57 to 0.79) <0.001 Surgical Interventions for BPH 10.1 4.6 0.45 (0.32 to 0.63) <0.001 Acute Urinary Retention Requiring Catheterization 6.6 2.8 0.43 (0.28 to 0.66) <0.001 Two consecutive symptom scores ≥20 9.2 6.7 Bladder Stone 0.4 0.5 Incontinence 2.1 1.7 Renal Failure 0.5 0.6 UTI 5.7 4.9 Discontinuation due to worsening of BPH, lack of improvement, or to receive other medical treatment 21.8 13.3 Compared with placebo, PROSCAR was associated with a significantly lower risk for acute urinary retention or the need for BPH-related surgery [13.2% for placebo vs 6.6% for PROSCAR; 51% reduction in risk, 95% CI: (34 to 63%)]. Compared with placebo, PROSCAR was associated with a significantly lower risk for surgery [10.1% for placebo vs 4.6% for PROSCAR; 55% reduction in risk, 95% CI: (37 to 68%)] and with a significantly lower risk of acute urinary retention [6.6% for placebo vs 2.8% for PROSCAR; 57% reduction in risk, 95% CI: (34 to 72%)]; see Figures 2 and 3 . Figure 2 Percent of Patients Having Surgery for BPH, Including TURP Figure 3 Percent of Patients Developing Acute Urinary Retention (Spontaneous and Precipitated) Effect on Maximum Urinary Flow Rate In the patients in PLESS who remained on therapy for the duration of the study and had evaluable urinary flow data, PROSCAR increased maximum urinary flow rate by 1.9 mL/sec compared with 0.2 mL/sec in the placebo group. There was a clear difference between treatment groups in maximum urinary flow rate in favor of PROSCAR by month 4 (1.0 vs 0.3 mL/sec) which was maintained throughout the study. In the earlier 1-year studies, increase in maximum urinary flow rate was comparable to PLESS and was maintained through the first year and throughout an additional 5 years of open extension studies. Effect on Prostate Volume In PLESS, prostate volume was assessed yearly by magnetic resonance imaging (MRI) in a subset of patients. In patients treated with PROSCAR who remained on therapy, prostate volume was reduced compared with both baseline and placebo throughout the 4-year study. PROSCAR decreased prostate volume by 17.9% (from 55.9 cc at baseline to 45.8 cc at 4 years) compared with an increase of 14.1% (from 51.3 cc to 58.5 cc) in the placebo group (p<0.001). (See Figure 4 .) Results seen in earlier studies were comparable to those seen in PLESS. Mean prostate volume at baseline ranged between 40-50 cc. The reduction in prostate volume was seen during the first year and maintained throughout an additional five years of open extension studies. Figure 4 Prostate Volume in PLESS Prostate Volume as a Predictor of Therapeutic Response A meta-analysis combining 1-year data from seven double-blind, placebo-controlled studies of similar design, including 4491 patients with symptomatic BPH, demonstrated that, in patients treated with PROSCAR, the magnitude of symptom response and degree of improvement in maximum urinary flow rate were greater in patients with an enlarged prostate at baseline.

om seven double-blind, placebo-controlled studies of similar design, including 4491 patients with symptomatic BPH, demonstrated that, in patients treated with PROSCAR, the magnitude of symptom response and degree of improvement in maximum urinary flow rate were greater in patients with an enlarged prostate at baseline. 14.2 Combination with Alpha-Blocker Therapy The Medical Therapy of Prostatic Symptoms (MTOPS) Trial was a double-blind, randomized, placebo-controlled, multicenter, 4- to 6-year study (average 5 years) in 3047 men with symptomatic BPH, who were randomized to receive PROSCAR 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), the combination of PROSCAR 5 mg/day and doxazosin 4 or 8 mg/day (n=786), or placebo (n=737). All participants underwent weekly titration of doxazosin (or its placebo) from 1 to 2 to 4 to 8 mg/day. Only those who tolerated the 4 or 8 mg dose level were kept on doxazosin (or its placebo) in the study. The participant's final tolerated dose (either 4 mg or 8 mg) was administered beginning at end-Week 4. The final doxazosin dose was administered once per day, at bedtime. The mean patient age at randomization was 62.6 years (±7.3 years). Patients were Caucasian (82%), African American (9%), Hispanic (7%), Asian (1%) or Native American (<1%). The mean duration of BPH symptoms was 4.7 years (±4.6 years). Patients had moderate to severe BPH symptoms at baseline with a mean AUA symptom score of approximately 17 out of 35 points. Mean maximum urinary flow rate was 10.5 mL/sec (±2.6 mL/sec). The mean prostate volume as measured by transrectal ultrasound was 36.3 mL (±20.1 mL). Prostate volume was ≤20 mL in 16% of patients, ≥50 mL in 18% of patients and between 21 and 49 mL in 66% of patients. The primary endpoint was a composite measure of the first occurrence of any of the following five outcomes: a ≥4 point confirmed increase from baseline in symptom score, acute urinary retention, BPH-related renal insufficiency (creatinine rise), recurrent urinary tract infections or urosepsis, or incontinence. Compared to placebo, treatment with PROSCAR, doxazosin, or combination therapy resulted in a reduction in the risk of experiencing one of these five outcome events by 34% (p=0.002), 39% (p<0.001), and 67% (p<0.001), respectively. Combination therapy resulted in a significant reduction in the risk of the primary endpoint compared to treatment with PROSCAR alone (49%; p≤0.001) or doxazosin alone (46%; p≤0.001). (See Table 6 .) Table 6: Count and Percent Incidence of Primary Outcome Events by Treatment Group in MTOPS Treatment Group Placebo Doxazosin Finasteride Combination Total N=737 N=756 N=768 N=786 N=3047 Event N (%) N (%) N (%) N (%) N (%) AUA 4-point rise 100 (13.6) 59 (7.8) 74 (9.6) 41 (5.2) 274 (9.0) Acute urinary retention 18 (2.4) 13 (1.7) 6 (0.8) 4 (0.5) 41 (1.3) Incontinence 8 (1.1) 11 (1.5) 9 (1.2) 3 (0.4) 31 (1.0) Recurrent UTI/urosepsis 2 (0.3) 2 (0.3) 0 (0.0) 1 (0.1) 5 (0.2) Creatinine rise 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Total Events 128 (17.4) 85 (11.2) 89 (11.6) 49 (6.2) 351 (11.5) The majority of the events (274 out of 351; 78%) was a confirmed ≥4 point increase in symptom score, referred to as symptom score progression. The risk of symptom score progression was reduced by 30% (p=0.016), 46% (p<0.001), and 64% (p<0.001) in patients treated with PROSCAR, doxazosin, or the combination, respectively, compared to patients treated with placebo (see Figure 5 ). Combination therapy significantly reduced the risk of symptom score progression compared to the effect of PROSCAR alone (p<0.001) and compared to doxazosin alone (p=0.037).

(p<0.001) in patients treated with PROSCAR, doxazosin, or the combination, respectively, compared to patients treated with placebo (see Figure 5 ). Combination therapy significantly reduced the risk of symptom score progression compared to the effect of PROSCAR alone (p<0.001) and compared to doxazosin alone (p=0.037). Figure 5 Cumulative Incidence of a 4-Point Rise in AUA Symptom Score by Treatment Group Treatment with PROSCAR, doxazosin or the combination of PROSCAR with doxazosin, reduced the mean symptom score from baseline at year 4. Table 7 provides the mean change from baseline for AUA symptom score by treatment group for patients who remained on therapy for four years. Table 7: Change From Baseline in AUA Symptom Score by Treatment Group at Year 4 in MTOPS Placebo N=534 Doxazosin N=582 Finasteride N=565 Combination N=598 Baseline Mean (SD) 16.8 (6.0) 17.0 (5.9) 17.1 (6.0) 16.8 (5.8) Mean Change AUA Symptom Score (SD) -4.9 (5.8) -6.6 (6.1) -5.6 (5.9) -7.4 (6.3) Comparison to Placebo (95% CI) -1.8 (-2.5, -1.1) -0.7 (-1.4, 0.0) -2.5 (-3.2, -1.8) Comparison to Doxazosin alone (95% CI) -0.7 (-1.4, 0.0) Comparison to Finasteride alone (95% CI) -1.8 (-2.5, -1.1) The results of MTOPS are consistent with the findings of the 4-year, placebo-controlled study PLESS [see Clinical Studies (14.1) ] in that treatment with PROSCAR reduces the risk of acute urinary retention and the need for BPH-related surgery. In MTOPS, the risk of developing acute urinary retention was reduced by 67% in patients treated with PROSCAR compared to patients treated with placebo (0.8% for PROSCAR and 2.4% for placebo). Also, the risk of requiring BPH-related invasive therapy was reduced by 64% in patients treated with PROSCAR compared to patients treated with placebo (2.0% for PROSCAR and 5.4% for placebo). 14.3 Summary of Clinical Studies The data from these studies, showing improvement in BPH-related symptoms, reduction in treatment failure (BPH-related urological events), increased maximum urinary flow rates, and decreasing prostate volume, suggest that PROSCAR arrests the disease process of BPH in men with an enlarged prostate. Image of Figure 1 Image of Figure 2 Image of Figure 3 Image of Figure 4 Image of Figure 5

<table ID="fig1" width="100%" styleCode="Noautorules"><caption>Figure 1 Symptom Score in PLESS</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM2"/></td></tr></tbody></table>

<table ID="fig1" width="100%" styleCode="Noautorules"><caption>Figure 1 Symptom Score in PLESS</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM2"/></td></tr></tbody></table> <table width="663.000" ID="Table5"><caption>Table 5: All Treatment Failures in PLESS</caption><col width="22.3%"/><col width="14.9%"/><col width="15.7%"/><col width="15.7%"/><col width="15.7%"/><col width="15.7%"/><thead><tr><th align="left" valign="top" styleCode="Botrule Lrule Rrule"/><th align="center" valign="top" colspan="2" styleCode="Botrule Lrule Rrule">Patients (%)<footnote ID="t5f1">patients with multiple events may be counted more than once for each type of event</footnote></th><th align="center" valign="top" styleCode="Botrule Lrule Rrule"/><th align="center" valign="top" styleCode="Botrule Lrule Rrule"/><th align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Event</th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Placebo N=1503</th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Finasteride N=1513</th><th align="left" valign="top" styleCode="Botrule Lrule Rrule">Relative Risk<footnote ID="t5f2">Hazard ratio based on log rank test</footnote></th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">95% CI</th><th align="center" valign="top" styleCode="Botrule Lrule Rrule">P Value<footnoteRef IDREF="t5f2"/></th></tr></thead><tbody><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">All Treatment Failures </td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">37.1</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">26.2</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.68</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">(0.57 to 0.79)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">&lt;0.001</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Surgical Interventions for BPH </td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">10.1</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">4.6</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.45</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">(0.32 to 0.63)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">&lt;0.001</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Acute Urinary Retention Requiring Catheterization</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">6.6</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">2.8</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.43</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">(0.28 to 0.66)</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">&lt;0.001</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Two consecutive symptom scores &#x2265;20</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">9.2</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">6.7</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Bladder Stone</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.4</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.5</td><td align="center" valign="top" styleCode="Botrule Lrule R

Code="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Bladder Stone</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.4</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.5</td><td align="center" valign="top" styleCode="Botrule Lrule R rule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Incontinence</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">2.1</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">1.7</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Renal Failure</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.5</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.6</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> UTI</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">5.7</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">4.9</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Discontinuation due to worsening of BPH, lack of improvement, or to receive other medical treatment</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">21.8</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">13.3</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr></tbody></table>

"Botrule Lrule Rrule">21.8</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule">13.3</td><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/></tr></tbody></table> <table ID="fig2" width="100%" styleCode="Noautorules"><caption>Figure 2 Percent of Patients Having Surgery for BPH, Including TURP</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM3"/></td></tr></tbody></table> <table ID="fig3" width="100%" styleCode="Noautorules"><caption>Figure 3 Percent of Patients Developing Acute Urinary Retention (Spontaneous and Precipitated)</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM4"/></td></tr></tbody></table> <table ID="fig4" width="100%" styleCode="Noautorules"><caption>Figure 4 Prostate Volume in PLESS</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM5"/></td></tr></tbody></table>

<table ID="fig3" width="100%" styleCode="Noautorules"><caption>Figure 3 Percent of Patients Developing Acute Urinary Retention (Spontaneous and Precipitated)</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM4"/></td></tr></tbody></table> <table ID="fig4" width="100%" styleCode="Noautorules"><caption>Figure 4 Prostate Volume in PLESS</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM5"/></td></tr></tbody></table> <table width="697.000" ID="Table6"><caption>Table 6: Count and Percent Incidence of Primary Outcome Events by Treatment Group in MTOPS</caption><col width="28.4%"/><col width="14.9%"/><col width="14.2%"/><col width="13.3%"/><col width="14.9%"/><col width="14.2%"/><thead><tr><th align="center" valign="bottom" styleCode="Toprule Lrule Rrule"/><th align="center" valign="bottom" colspan="5" styleCode="Botrule Lrule Rrule">Treatment Group</th></tr><tr><th align="center" valign="bottom" styleCode="Lrule Rrule"/><th align="center" valign="bottom" styleCode="Lrule Rrule">Placebo</th><th align="center" valign="bottom" styleCode="Lrule Rrule">Doxazosin</th><th align="center" valign="bottom" styleCode="Lrule Rrule">Finasteride</th><th align="center" valign="bottom" styleCode="Lrule Rrule">Combination</th><th align="center" valign="bottom" styleCode="Lrule Rrule">Total</th></tr><tr><th align="center" valign="bottom" styleCode="Lrule Rrule"/><th align="center" valign="bottom" styleCode="Lrule Rrule">N=737</th><th align="center" valign="bottom" styleCode="Lrule Rrule">N=756</th><th align="center" valign="bottom" styleCode="Lrule Rrule">N=768</th><th align="center" valign="bottom" styleCode="Lrule Rrule">N=786</th><th align="center" valign="bottom" styleCode="Lrule Rrule">N=3047</th></tr><tr><th align="center" valign="bottom" styleCode="Botrule Lrule Rrule">Event</th><th align="center" valign="bottom" styleCode="Botrule Rrule">N (%)</th><th align="center" valign="bottom" styleCode="Botrule Rrule">N (%)</th><th align="center" valign="bottom" styleCode="Botrule Rrule">N (%)</th><th align="center" valign="bottom" styleCode="Botrule Rrule">N (%)</th><th align="center" valign="bottom" styleCode="Botrule Lrule Rrule">N (%)</th></tr></thead><tbody><tr><td align="left" valign="top" styleCode="Lrule Rrule">AUA 4-point rise</td><td align="center" valign="bottom" styleCode="Rrule">100 (13.6)</td><td align="center" valign="bottom" styleCode="Rrule">59 (7.8)</td><td align="center" valign="bottom" styleCode="Rrule">74 (9.6)</td><td align="center" valign="bottom" styleCode="Rrule">41 (5.2)</td><td align="center" valign="bottom" styleCode="Lrule Rrule">274 (9.0)</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule">Acute urinary retention</td><td align="center" valign="bottom" styleCode="Rrule">18 (2.4)</td><td align="center" valign="bottom" styleCode="Rrule">13 (1.7)</td><td align="center" valign="bottom" styleCode="Rrule">6 (0.8)</td><td align="center" valign="bottom" styleCode="Rrule">4 (0.5)</td><td align="center" valign="bottom" styleCode="Lrule Rrule">41 (1.3)</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule">Incontinence</td><td align="center" valign="bottom" styleCode="Rrule">8 (1.1)</td><td align="center" valign="bottom" styleCode="Rrule">11 (1.5)</td><td align="center" valign="bottom" styleCode="Rrule">9 (1.2)</td><td align="center" valign="bottom" styleCode="Rrule">3 (0.4)</td><td align="center" valign="bottom" styleCode="Lrule Rrule">31 (1.0)</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule">Recurrent UTI/urosepsis</td><td align="center" valign="bottom" styleCode="Rrule">2 (0.3)</td><td align="center" valign="bottom" styleCode="Rrule">2 (0.3)</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Rrule">1 (0.1)</td><td align="center" valign="bottom" styleCode="Lrule Rrule">5 (0.2)</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule">Cre

enter" valign="bottom" styleCode="Rrule">2 (0.3)</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Rrule">1 (0.1)</td><td align="center" valign="bottom" styleCode="Lrule Rrule">5 (0.2)</td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule">Cre atinine rise</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Lrule Rrule">0 (0.0)</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Total Events</td><td align="center" valign="bottom" styleCode="Rrule">128 (17.4)</td><td align="center" valign="bottom" styleCode="Rrule">85 (11.2)</td><td align="center" valign="bottom" styleCode="Rrule">89 (11.6)</td><td align="center" valign="bottom" styleCode="Rrule">49 (6.2)</td><td align="center" valign="bottom" styleCode="Botrule Lrule Rrule">351 (11.5)</td></tr></tbody></table> <table ID="fig5" width="100%" styleCode="Noautorules"><caption>Figure 5 Cumulative Incidence of a 4-Point Rise in AUA Symptom Score by Treatment Group</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM6"/></td></tr></tbody></table>

atinine rise</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Rrule">0 (0.0)</td><td align="center" valign="bottom" styleCode="Lrule Rrule">0 (0.0)</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Total Events</td><td align="center" valign="bottom" styleCode="Rrule">128 (17.4)</td><td align="center" valign="bottom" styleCode="Rrule">85 (11.2)</td><td align="center" valign="bottom" styleCode="Rrule">89 (11.6)</td><td align="center" valign="bottom" styleCode="Rrule">49 (6.2)</td><td align="center" valign="bottom" styleCode="Botrule Lrule Rrule">351 (11.5)</td></tr></tbody></table> <table ID="fig5" width="100%" styleCode="Noautorules"><caption>Figure 5 Cumulative Incidence of a 4-Point Rise in AUA Symptom Score by Treatment Group</caption><col width="100%" align="center" valign="top"/><tbody><tr><td><renderMultiMedia referencedObject="MM6"/></td></tr></tbody></table> <table width="626.000" ID="Table7"><caption>Table 7: Change From Baseline in AUA Symptom Score by Treatment Group at Year 4 in MTOPS</caption><col width="35.9%"/><col width="16.6%"/><col width="15.8%"/><col width="15.8%"/><col width="15.8%"/><thead><tr><th align="left" valign="top" styleCode="Botrule Toprule Lrule Rrule"/><th align="center" valign="top" styleCode="Botrule Lrule Rrule">Placebo N=534</th><th align="center" valign="top" styleCode="Botrule Rrule">Doxazosin N=582</th><th align="center" valign="top" styleCode="Botrule Rrule">Finasteride N=565</th><th align="center" valign="top" styleCode="Botrule Rrule">Combination N=598</th></tr></thead><tbody><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule">Baseline Mean (SD) </td><td align="center" valign="middle" styleCode="Botrule Rrule">16.8 (6.0) </td><td align="center" valign="middle" styleCode="Botrule Rrule">17.0 (5.9)</td><td align="center" valign="middle" styleCode="Botrule Rrule">17.1 (6.0)</td><td align="center" valign="middle" styleCode="Botrule Rrule">16.8 (5.8)</td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule">Mean Change AUA Symptom Score (SD)</td><td align="center" valign="middle" styleCode="Botrule Rrule">-4.9 (5.8)</td><td align="center" valign="middle" styleCode="Botrule Rrule">-6.6 (6.1)</td><td align="center" valign="middle" styleCode="Botrule Rrule">-5.6 (5.9)</td><td align="center" valign="middle" styleCode="Botrule Rrule">-7.4 (6.3)</td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule">Comparison to Placebo (95% CI)</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule">-1.8 (-2.5, -1.1)</td><td align="center" valign="top" styleCode="Botrule Rrule">-0.7 (-1.4, 0.0)</td><td align="center" valign="top" styleCode="Botrule Rrule">-2.5 (-3.2, -1.8)</td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule">Comparison to Doxazosin alone (95% CI)</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule">-0.7 (-1.4, 0.0)</td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule">Comparison to Finasteride alone (95% CI)</td><td align="center" valign="top" styleCode="Rrule"/><td align="center" valign="top" styleCode="Rrule"/><td align="center" valign="top" styleCode="Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule">-1.8 (-2.5, -1.1)</td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING PROSCAR tablets 5 mg are blue, modified apple-shaped, film-coated tablets, with the code MSD 72 on one side and PROSCAR on the other. They are supplied as follows: NDC 78206-153-01 unit of use bottles of 30 NDC 78206-153-02 unit of use bottles of 100. Storage and Handling Store at room temperatures below 30°C (86°F). Protect from light and keep container tightly closed. Females should not handle crushed or broken PROSCAR tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1) ].

Storage and Handling Store at room temperatures below 30°C (86°F). Protect from light and keep container tightly closed. Females should not handle crushed or broken PROSCAR tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1) ].

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Increased Risk of High-Grade Prostate Cancer Patients should be informed that there was an increase in high-grade prostate cancer in men treated with 5α-reductase inhibitors indicated for BPH treatment, including PROSCAR, compared to those treated with placebo in studies looking at the use of these drugs to prevent prostate cancer [see Indications and Usage (1.3) , Warnings and Precautions (5.2) , and Adverse Reactions (6.1) ]. Exposure of Females — Risk to Male Fetus Physicians should inform patients that females who are pregnant or may potentially be pregnant should not handle crushed or broken PROSCAR tablets because of the possibility of absorption of finasteride and the subsequent potential risk to the male fetus. PROSCAR tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed. If a female who is pregnant or may potentially be pregnant comes in contact with crushed or broken PROSCAR tablets, the contact area should be washed immediately with soap and water [see Contraindications (4) , Warnings and Precautions (5.3) , Use in Specific Populations (8.1) and How Supplied/Storage and Handling (16) ]. Additional Instructions Physicians should inform patients that the volume of ejaculate may be decreased in some patients during treatment with PROSCAR. This decrease does not appear to interfere with normal sexual function. However, impotence and decreased libido may occur in patients treated with PROSCAR [see Adverse Reactions (6.1) ] . Physicians should instruct their patients to promptly report any changes in their breasts such as lumps, pain or nipple discharge. Breast changes including breast enlargement, tenderness and neoplasm have been reported [see Adverse Reactions (6.1) ] . Physicians should instruct their patients to read the patient package insert before starting therapy with PROSCAR and to reread it each time the prescription is renewed so that they are aware of current information for patients regarding PROSCAR.

Dist. by: Organon LLC, a subsidiary of ORGANON & Co., Jersey City, NJ 07302, USA For patent information: www.organon.com/our-solutions/patent/ © 2026 Organon group of companies. All rights reserved. uspi-og0906-5t-2603r004 Dist. by: Organon LLC, a subsidiary of ORGANON & Co., Jersey City, NJ 07302, USA For patent information: www.organon.com/our-solutions/patent/ © 2026 Organon group of companies. All rights reserved. Revised: 03/2026 usppi-og0906-5t-2603r003

PROSCAR ® (finasteride) Tablets Patient Information about PROSCAR ® (Prahs-car) Generic name: finasteride (fin-AS-tur-eyed) PROSCAR is for use by men only. Please read this leaflet before you start taking PROSCAR. Also, read it each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss PROSCAR when you start taking your medication and at regular checkups. What is PROSCAR? PROSCAR is a medication used to treat symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate. PROSCAR may also be used to reduce the risk of a sudden inability to pass urine and the need for surgery related to BPH in men with an enlarged prostate. PROSCAR may be prescribed along with another medicine, an alpha-blocker called doxazosin, to help you better manage your BPH symptoms. Who should NOT take PROSCAR? PROSCAR is for use by MEN only. Do Not Take PROSCAR if you are: a woman who is pregnant or may potentially be pregnant. PROSCAR may harm your unborn baby. Do not touch or handle crushed or broken PROSCAR tablets (see " A warning about PROSCAR and pregnancy " ). allergic to finasteride or any of the ingredients in PROSCAR. See the end of this leaflet for a complete list of ingredients in PROSCAR. A warning about PROSCAR and pregnancy: Women who are or may potentially be pregnant must not use PROSCAR. They should also not handle crushed or broken tablets of PROSCAR. PROSCAR tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets are not broken or crushed. If a woman who is pregnant with a male baby absorbs the active ingredient in PROSCAR after oral use or through the skin, it may cause the male baby to be born with abnormalities of the sex organs. If a woman who is pregnant comes into contact with the active ingredient in PROSCAR, a doctor should be consulted. How should I take PROSCAR? Follow your doctor's instruction. Take one tablet by mouth each day. To avoid forgetting to take PROSCAR, you can take it at the same time every day. If you forget to take PROSCAR, do not take an extra tablet. Just take the next tablet as usual. You may take PROSCAR with or without food. Do not share PROSCAR with anyone else; it was prescribed only for you. What are the possible side effects of PROSCAR? PROSCAR may increase the chance of a more serious form of prostate cancer. The most common side effects of PROSCAR include: trouble getting or keeping an erection (impotence) decrease in sex drive decreased volume of ejaculate ejaculation disorders enlarged or painful breast. You should promptly report to your doctor any changes in your breasts such as lumps, pain or nipple discharge. The following have been reported in general use with PROSCAR and/or finasteride at lower doses: allergic reactions, including rash, itching, hives, and swelling of the lips, tongue, throat, and face rarely, some men may have testicular pain blood in semen trouble getting or keeping an erection that continued after stopping the medication problems with ejaculation that continued after stopping the medication male infertility and/or poor quality of semen. Improvement in the quality of semen has been reported after stopping the medication.

ve testicular pain blood in semen trouble getting or keeping an erection that continued after stopping the medication problems with ejaculation that continued after stopping the medication male infertility and/or poor quality of semen. Improvement in the quality of semen has been reported after stopping the medication. depression suicidal thoughts decrease in sex drive that continued after stopping the medication in rare cases, male breast cancer has been reported. You should discuss side effects with your doctor before taking PROSCAR and anytime you think you are having a side effect. These are not all the possible side effects with PROSCAR. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at: 1-800-FDA-1088. What you need to know while taking PROSCAR: You should see your doctor regularly while taking PROSCAR. Follow your doctor's advice about when to have these checkups. Checking for prostate cancer. Your doctor has prescribed PROSCAR for BPH and not for treatment of prostate cancer — but a man can have BPH and prostate cancer at the same time. Your doctor may continue checking for prostate cancer while you take PROSCAR. About Prostate-Specific Antigen (PSA). Your doctor may have done a blood test called PSA for the screening of prostate cancer. Because PROSCAR decreases PSA levels, you should tell your doctor(s) that you are taking PROSCAR. Changes in PSA levels will need to be evaluated by your doctor(s). Any increase in follow-up PSA levels from their lowest point may signal the presence of prostate cancer and should be evaluated, even if the test results are still within the normal range. You should also tell your doctor if you have not been taking PROSCAR as prescribed because this may affect the PSA test results. For more information, talk to your doctor. How should I store PROSCAR? Store PROSCAR tablets in a dry place at room temperature. Keep PROSCAR in the original container and keep the container closed. PROSCAR tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets are not broken or crushed. Keep PROSCAR and all medications out of the reach of children. Do not give your PROSCAR tablets to anyone else. It has been prescribed only for you. For more information call 1-844-674-3200. What are the ingredients in PROSCAR? Active ingredients: finasteride Inactive ingredients: hydrous lactose, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, hydroxypropyl cellulose LF, hydroxypropyl methylcellulose, titanium dioxide, magnesium stearate, talc, docusate sodium, FD&C Blue 2 aluminum lake and yellow iron oxide. What is BPH? BPH is an enlargement of the prostate gland. The prostate is located below the bladder. As the prostate enlarges, it may slowly restrict the flow of urine. This can lead to symptoms such as: a weak or interrupted urinary stream a feeling that you cannot empty your bladder completely a feeling of delay or hesitation when you start to urinate a need to urinate often, especially at night a feeling that you must urinate right away. In some men, BPH can lead to serious problems, including urinary tract infections, a sudden inability to pass urine (acute urinary retention), as well as the need for surgery. What PROSCAR does: PROSCAR lowers levels of a hormone called DHT (dihydrotestosterone), which is a cause of prostate growth. Lowering DHT leads to shrinkage of the enlarged prostate gland in most men. This can lead to gradual improvement in urine flow and symptoms over the next several months. PROSCAR will help reduce the risk of developing a sudden inability to pass urine and the need for surgery related to an enlarged prostate.

ate growth. Lowering DHT leads to shrinkage of the enlarged prostate gland in most men. This can lead to gradual improvement in urine flow and symptoms over the next several months. PROSCAR will help reduce the risk of developing a sudden inability to pass urine and the need for surgery related to an enlarged prostate. However, since each case of BPH is different, you should know that: Even though the prostate shrinks, you may NOT notice an improvement in urine flow or symptoms. You may need to take PROSCAR for six (6) months or more to see whether it improves your symptoms. Therapy with PROSCAR may reduce your risk for a sudden inability to pass urine and the need for surgery for an enlarged prostate.

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