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DESCRIPTION Norethindrone acetate tablets, USP - 5 mg oral tablets. Norethindrone acetate, USP (17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one acetate), a synthetic, orally active progestin, is the acetic acid ester of norethindrone, USP. It is a white, or creamy white, crystalline powder. Norethindrone acetate tablets, USP contain the following inactive ingredients: lactose, magnesium stearate, and microcrystalline cellulose. cd236b39-figure-01

CLINICAL PHARMACOLOGY Norethindrone acetate induces secretory changes in an estrogen-primed endometrium. On a weight basis, it is twice as potent as norethindrone. Pharmacokinetics Absorption Norethindrone acetate is completely and rapidly deacetylated to norethindrone (NET) after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate is rapidly absorbed from norethindrone acetate tablets, with maximum plasma concentration of norethindrone generally occurring at about 2 hours post-dose. The pharmacokinetic parameters of norethindrone following single oral administration of norethindrone acetate in 29 healthy female volunteers are summarized in Table 1. Table 1.Pharmacokinetic Parameters after a Single Dose of Norethindrone Acetate in Healthy Women Norethindrone Acetate (n=29) Arithmetic Mean ± SD Norethindrone (NET) AUC = area under the curve, C max = maximum plasma concentration, t max = time at maximum plasma concentration, t 1/2 = half-life, SD = standard deviation AUC (0-inf) (ng/ml*h) 166.90 ± 56.28 C max (ng/ml) 26.19 ± 6.19 t max (h) 1.83 ± 0.58 t 1/2 (h) 8.51 ± 2.19 Figure 1. Mean Plasma Concentration Profile after a Single Dose of 5 mg Administered to 29 Healthy Female Volunteers under Fasting Conditions Effect of Food The effect of food administration on the pharmacokinetics of norethindrone acetate has not been studied. Distribution Norethindrone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Volume of distribution of norethindrone is about 4 L/kg. Metabolism Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites. Excretion Plasma clearance value for norethindrone is approximately 0.4 L/hr/kg. Norethindrone is excreted in both urine and feces, primarily as metabolites. The mean terminal elimination half-life of norethindrone following a single dose administration of norethindrone acetate is approximately 9 hours. Special Populations Geriatrics The effect of age on the pharmacokinetics of norethindrone after norethindrone acetate administration has not been evaluated. Race The effect of race on the disposition of norethindrone after norethindrone acetate administration has not been evaluated. Renal Insufficiency The effect of renal disease on the disposition of norethindrone after norethindrone acetate administration has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma norethindrone concentration was unchanged compared to concentrations in premenopausal women with normal renal function. Hepatic Insufficiency The effect of hepatic disease on the disposition of norethindrone after norethindrone acetate administration has not been evaluated. However, norethindrone acetate is contraindicated in markedly impaired liver function or liver disease. Drug Interactions No pharmacokinetic drug interaction studies investigating any drug-drug interactions with norethindrone acetate have been conducted. cd236b39-figure-02

INDICATIONS AND USAGE Norethindrone acetate tablets, USP is indicated for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. Norethindrone acetate tablets, USP are not intended, recommended or approved to be used with concomitant estrogen therapy in postmenopausal women for endometrial protection.

CONTRAINDICATIONS Known or suspected pregnancy. There is no indication for norethindrone acetate, USP in pregnancy. (See PRECAUTIONS .) Undiagnosed vaginal bleeding Known, suspected or history of cancer of the breast Active deep vein thrombosis, pulmonary embolism or history of these conditions Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction) Impaired liver function or liver disease As a diagnostic test for pregnancy Hypersensitivity to any of the drug components

WARNINGS 1. Cardiovascular disorders Patients with risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. 2. Visual abnormalities Discontinue medication pending examination if there is a sudden partial or complete loss of vision or if there is sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, medication should be discontinued.

PRECAUTIONS General Precautions Because this drug may cause some degree of fluid retention, conditions which might be influenced by this factor, such as epilepsy, migraine, cardiac or renal dysfunctions, require careful observation. In cases of breakthrough bleeding, and in all cases of irregular bleeding per vagina, nonfunctional causes should be borne in mind. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures are indicated. Patients who have a history of clinical depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree. Data suggest that progestin therapy may have adverse effects on lipid and carbohydrate metabolism. The choice of progestin, its dose, and its regimen may be important in minimizing these adverse effects, but these issues will require further study before they are clarified. Women with hyperlipidemias and/or diabetes should be monitored closely during progestin therapy. The pathologist should be advised of progestin therapy when relevant specimens are submitted. Information for the Patient Healthcare providers are advised to discuss the PATIENT INFORMATION leaflet with patients for whom they prescribe norethindrone acetate. Drug/Laboratory Test Interactions The following laboratory test results may be altered by the use of estrogen/progestin combination drugs: Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor X a and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T 4 levels (by column or by radioimmunoassay) or T 3 levels by radioimmunoassay. T 3 resin uptake is decreased, reflecting the elevated TBG. Free T 4 and free T 3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone. Other binding proteins may be elevated in serum (i.e., corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG)) leading to increased circulating corticosteroid and sex steroids, respectively. Free or biologically active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin). Increased plasma HDL and HDL 2 cholesterol subfraction concentrations, reduced LDL cholesterol concentration, increased triglycerides levels. Impaired glucose metabolism. Reduced response to metyrapone test. Carcinogenesis, Mutagenesis, Impairment of Fertility Some beagle dogs treated with medroxyprogesterone acetate developed mammary nodules. Although nodules occasionally appeared in control animals, they were intermittent in nature, whereas nodules in treated animals were larger and more numerous, and persisted. There is no general agreement as to whether the nodules are benign or malignant. Their significance with respect to humans has not been established. Pregnancy Pregnancy Category X Norethindrone acetate is contraindicated during pregnancy as it may cause fetal harm when administered to pregnant women.

us, and persisted. There is no general agreement as to whether the nodules are benign or malignant. Their significance with respect to humans has not been established. Pregnancy Pregnancy Category X Norethindrone acetate is contraindicated during pregnancy as it may cause fetal harm when administered to pregnant women. Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and congenital abnormalities in male and female fetuses. Some progestational drugs induce mild virilization of the external genitalia of female fetuses. Nursing Mothers Detectable amounts of progestins have been identified in the milk of mothers receiving them. Caution should be exercised when progestins are administered to a nursing woman. Pediatric Use Norethindrone acetate tablets are not indicated in children.

ADVERSE REACTIONS See WARNINGS and PRECAUTIONS . The following adverse reactions have been observed in women taking progestins: Breakthrough bleeding Spotting Change in menstrual flow Amenorrhea Edema Changes in weight (decreases, increases) Changes in the cervical squamo-columnar junction and cervical secretions Cholestatic jaundice Rash (allergic) with and without pruritus Melasma or chloasma Clinical depression Acne Breast enlargement/tenderness Headache/migraine Urticaria Abnormalities of liver tests (i.e., AST, ALT, Bilirubin) Decreased HDL cholesterol and increased LDL/HDL ratio Mood swings Nausea Insomnia Anaphylactic/anaphylactoid reactions Thrombotic and thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, cerebral thrombosis and embolism) Optic neuritis (which may lead to partial or complete loss of vision) To report SUSPECTED ADVERSE REACTIONS contact AvKARE at 1-855-361-3993; email drugsafety@avkare.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DOSAGE AND ADMINISTRATION Therapy with norethindrone acetate tablets, USP must be adapted to the specific indications and therapeutic response of the individual patient. Secondary amenorrhea, abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology: 2.5 to 10 mg norethindrone acetate, USP may be given daily for 5 to 10 days to produce secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing norethindrone acetate, USP therapy. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with norethindrone acetate tablets, USP. Endometriosis: Initial daily dosage of 5 mg norethindrone acetate, USP for two weeks. Dosage should be increased by 2.5 mg per day every two weeks until 15 mg per day of norethindrone acetate, USP is reached. Therapy may be held at this level for six to nine months or until annoying breakthrough bleeding demands temporary termination.

HOW SUPPLIED Norethindrone acetate tablets, USP, 5 mg, are supplied as white to off-white oval, biconvex tablets debossed with “AN” bisect “475” on one side and plain on the other side. They are available as follows: Bottles of 90: NDC 42291-650-90 Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. All registered trademarks in this document are the property of their respective owners.

PATIENT INFORMATION Norethindrone Acetate Tablets Read this PATIENT INFORMATION before you start taking norethindrone acetate tablets and read what you get each time you refill norethindrone acetate tablets. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition. What is the most important information I should know about norethindrone acetate (A Progestin Hormone) tablets? Do not use norethindrone acetate if you are pregnant, breastfeeding or are trying to conceive. Do not use norethindrone acetate if you have had a previous blood clot, stroke, or heart attack. Do not use norethindrone acetate if you are postmenopausal. What is norethindrone acetate? Norethindrone acetate is similar to the progesterone hormones naturally produced by the body. What are norethindrone acetate tablets used for? Norethindrone acetate tablets are used for the treatment of secondary amenorrhea (absence of menstrual periods in women who have previously had a menstrual period who are not pregnant), the treatment of endometriosis, and the treatment of irregular menstrual periods due to hormone imbalance. Who should not take norethindrone acetate tablets? You should not take norethindrone acetate tablets if you are postmenopausal, pregnant or breast-feeding. You should not take norethindrone acetate tablets if you have the following conditions: Known or suspected pregnancy . Norethindrone acetate tablets are not indicated during pregnancy as it may cause fetal harm when administered to pregnant women. There is an increased risk of minor birth defects in children whose mothers take norethindrone acetate during the first 4 months of pregnancy (mild masculinization of the external genitalia of the female fetus, as well as hypospadias in the male fetus). If you take norethindrone acetate and later find out you were pregnant, talk with your healthcare provider right away. History of blood clots in the legs, lungs, eyes, brain, or elsewhere, or a past history of these conditions Liver impairment or disease Known or suspected cancer of the breast. If you have or had cancer of the breast, talk with your healthcare provider about whether you should take norethindrone acetate. Undiagnosed vaginal bleeding Hypersensitivity to norethindrone acetate tablets. See the end of this leaflet for a list of all of the ingredients in norethindrone acetate tablets. What are the risks associated with norethindrone acetate tablets? Risk to the Fetus Norethindrone acetate tablets should not be used if you are pregnant. Norethindrone acetate tablets are contraindicated during pregnancy as it may cause fetal harm when administered to pregnant women. There is an increased risk of minor birth defects in children whose mothers take this drug during the first 4 months of pregnancy. Several reports suggest an association between mothers who take these drugs in the first trimester of pregnancy and congenital abnormalities in male and female babies. Although it is not clear that these events were drug related, you should check with your healthcare provider about the risks to your unborn child of any medication taken during pregnancy. You should avoid using norethindrone acetate tablets during pregnancy. If you take norethindrone acetate tablets and later find you were pregnant when you took it, be sure to discuss this with your healthcare provider as soon as possible.

er about the risks to your unborn child of any medication taken during pregnancy. You should avoid using norethindrone acetate tablets during pregnancy. If you take norethindrone acetate tablets and later find you were pregnant when you took it, be sure to discuss this with your healthcare provider as soon as possible. Abnormal Blood Clotting Use of progestational drugs, such as norethindrone acetate, has been associated with changes in the blood-clotting system. These changes allow the blood to clot more easily, possibly allowing clots to form in the bloodstream. If blood clots do form in your bloodstream, they can cut off the blood supply to vital organs, causing serious problems. These problems may include a stroke (by cutting off blood to part of the brain), a heart attack (by cutting off blood to part of the heart), a pulmonary embolus (by cutting off blood to part of the lungs), visual loss or blindness (by cutting off blood vessels in the eye), or other problems. Any of these conditions may cause death or serious long-term disability. Call your healthcare provider right away if you suspect you have any of these conditions. He or she may advise you to stop using the drug. Eye Abnormalities Discontinue norethindrone acetate tablets and call your healthcare provider right away if you experience sudden partial or complete loss of vision, blurred vision, or sudden onset of bulging eyes, double vision, or migraine. These are some of the warning signs of serious side effects with progestin therapy Breast lumps Dizziness and faintness Changes in speech Severe headaches Chest pain Shortness of breath Pains in your legs Changes in vision Call your healthcare provider right away if you get any of these warning signs, or any other unusual symptom that concerns you. Common side effects include Headache Breast pain Irregular vaginal bleeding or spotting Stomach/abdominal cramps/bloating Nausea and vomiting Hair loss Other side effects include High blood pressure Liver problems High blood sugar Fluid retention Enlargements of benign tumors of the uterus (“fibroids”) Vaginal yeast infections Mental depression These are not all the possible side effects of progestin and/or estrogen therapy. For more information, ask your healthcare provider or pharmacist. What can I do to lower my chances of getting a serious side effect with norethindrone acetate? Talk with your healthcare provider regularly about whether you should continue taking norethindrone acetate. Have a breast exam and mammogram (breast x-ray) every year unless your healthcare provider tells you something else. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often. If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease. Ask your healthcare provider for ways to lower your chances of getting heart attacks. General information about the safe and effective use of norethindrone acetate tablets Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not take norethindrone acetate tablets for conditions for which it was not prescribed. Do not give norethindrone acetate tablets to other people, even if they have the same symptoms you have. It may harm them. Keep norethindrone acetate tablets out of the reach of children. This leaflet provides a summary of the most important information about progestin and/or estrogen therapy. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about norethindrone acetate that is written for health professionals.

out of the reach of children. This leaflet provides a summary of the most important information about progestin and/or estrogen therapy. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about norethindrone acetate that is written for health professionals. What are the ingredients in norethindrone acetate tablets? Norethindrone acetate tablets contain the following inactive ingredients: lactose, magnesium stearate, and microcrystalline cellulose.

DESCRIPTION Each tablet contains 0.35 mg norethindrone, USP. Inactive ingredients include colloidal silicon dioxide, corn starch, D&C Yellow No. 10, ethyl cellulose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, methylene chloride, isopropyl alcohol and talc. structure

CLINICAL PHARMACOLOGY 1. Mode of Action Norethindrone progestin-only oral contraceptives prevent conception by suppressing ovulation in approximately half of users, thickening the cervical mucus to inhibit sperm penetration, lowering the midcycle LH and FSH peaks, slowing the movement of the ovum through the fallopian tubes and altering the endometrium. 2. Pharmacokinetics Serum progestin levels peak about two hours after oral administration, followed by rapid distribution and elimination. By 24 hours after drug ingestion, serum levels are near baseline, making efficacy dependent upon rigid adherence to the dosing schedule. There are large variations in serum levels among individual users. Progestin-only administration results in lower steady-state serum progestin levels and a shorter elimination half-life than concomitant administration with estrogens.

1. Mode of Action Norethindrone progestin-only oral contraceptives prevent conception by suppressing ovulation in approximately half of users, thickening the cervical mucus to inhibit sperm penetration, lowering the midcycle LH and FSH peaks, slowing the movement of the ovum through the fallopian tubes and altering the endometrium.

2. Pharmacokinetics Serum progestin levels peak about two hours after oral administration, followed by rapid distribution and elimination. By 24 hours after drug ingestion, serum levels are near baseline, making efficacy dependent upon rigid adherence to the dosing schedule. There are large variations in serum levels among individual users. Progestin-only administration results in lower steady-state serum progestin levels and a shorter elimination half-life than concomitant administration with estrogens.

INDICATIONS AND USAGE 1. Indications Progestin-only oral contraceptives are indicated for the prevention of pregnancy. 2. Efficacy If used perfectly, the first-year failure rate for progestin-only oral contraceptives is 0.3%. However, the typical failure rate is estimated to be closer to 9%, due to late or omitted pills. Table 1 lists the pregnancy rates for users of all major methods of contraception. Table 1: Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year. United States. Emergency Contraception: Emergency contraceptive pills or insertion of a copper intrauterine contraceptive after unprotected intercourse substantially reduces the risk of pregnancy. 9 (See Chapter 6.). Lactational Amenorrhea Method: LAM is highly effective, temporary method of contraception 10 (See Chapter 18.). Source: Trussell J. Contraceptive Efficacy. In Hatcher RA, Trussell J, Nelson AL, Cates W, Kowal D, Policar M. Contraceptive Techology: Twentieth Revised Edition. New York NY: Ardent Media, 2011. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year Method (1) Typical Use (2) Perfect Use (3) (4) No method 4 85 85 Spermicides 28 18 42 Fertility awareness-based methods 24 47 Standard Days method 6 5 TwoDay method 6 4 Ovulation method 6 3 Symptothermal method 6 0.4 Withdrawal 22 4 46 Sponge 36 Parous women 24 20 Nulliparous women 12 9 Condom 7 Female (fc) 21 5 41 Male 18 2 43 Diaphragm 8 12 6 57 Combined pill and progestin-only pill 9 0.3 67 Norelgestromin and ethinyl estradiol patch 9 0.3 67 NuvaRing 9 0.3 67 Depo-Provera 6 0.2 56 Intrauterine contraceptives ParaGard (copper T) 0.8 0.6 78 Mirena (LNg) 0.2 0.2 80 Implanon 0.05 0.05 84 Female sterilization 0.5 0.5 100 Male sterilization 0.15 0.10 100 Notes: 1. Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. Estimates of the probability of pregnancy during the first year of typical use for spermicides, withdrawal, fertility awareness-based methods, the diaphragm, the male condom, the oral contraceptive pill, and Depo-Provera are taken from the 1995 National Survey of Family Growth corrected for underreporting of abortion; see the text for the derivation of estimates for the other methods. 2. Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. See the text for the derivation of the estimate for each method. 3. Among couples attempting to avoid pregnancy, the percentage who continue to use a method for 1 year. 4. The percentages becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within 1 year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within 1 year among women now relying on reversible methods of contraception if they abandoned contraception altogether. 5.

tion in order to become pregnant. Among such populations, about 89% become pregnant within 1 year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within 1 year among women now relying on reversible methods of contraception if they abandoned contraception altogether. 5. Foams, creams, gels, vaginal suppositories, and vaginal film. 6. The Ovulation and TwoDay methods are based on evaluation of cervical mucus. The Standard Days method avoids intercourse on cycle days 8 through 19. The Symptothermal method is a double-check method based on evaluation of cervical mucus to determine the first fertile day and evaluation of cervical mucus and temperature to determine the last fertile day. 7. Without spermicides. 8. With spermicidal cream or jelly. 9. ella, Plan B One-Step and Next Choice are the only dedicated products specifically marketed for emergency contraception. The label for Plan B One-Step (one dose is 1 white pill) says to take the pill within 72 hours after unprotected intercourse. Research has shown that all of the brands listed here are effective when used within 120 hours after unprotected sex. The label for Next Choice (one dose is 1 peach pill) says to take 1 pill within 72 hours after unprotected intercourse and another pill 12 hours later. Research has shown that both pills can be taken at the same time with no decrease in efficacy or increase in side effects and that they are effective when used within 120 hours after unprotected sex. The FDA has in addition declared the following 19 brands of oral contraceptives to be safe and effective for emergency contraception: Ogestrel (1 dose is 2 white pills), Nordette (1 dose is 4 light-orange pills), Cryselle, Levora, Low-Ogestrel, Lo/Ovral, or Quasence (1 dose is 4 white pills), Jolessa, Portia, Seasonale or Trivora (1 dose is 4 pink pills), Seasonique (1 dose is 4 light-blue-green pills), Enpresse (one dose is 4 orange pills), Lessina (1 dose is 5 pink pills), Aviane or LoSeasonique (one dose is 5 orange pills), Lutera or Sronyx (one dose is 5 white pills), and Lybrel (one dose is 6 yellow pills). Norethindrone tablets have not been studied for and are not indicated for use in emergency contraception.

<table ID="_Refid_644c1e8f-2a03-4a2f-b0f2-d6e6cab18" width="100%"><caption>Table 1: Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year. United States.</caption><col width="38%"/><col width="19%"/><col width="19%"/><col width="23%"/><tfoot><tr><td align="left" colspan="4" valign="top">Emergency Contraception: Emergency contraceptive pills or insertion of a copper intrauterine contraceptive after unprotected intercourse substantially reduces the risk of pregnancy.⁹(See Chapter 6.). </td></tr><tr><td align="left" colspan="4" valign="top">Lactational Amenorrhea Method: LAM is highly effective, temporary method of contraception 10 (See Chapter 18.). </td></tr><tr><td align="left" colspan="4" valign="top">Source: Trussell J. Contraceptive Efficacy. In Hatcher RA, Trussell J, Nelson AL, Cates W, Kowal D, Policar M. Contraceptive Techology: Twentieth Revised Edition.

l Amenorrhea Method: LAM is highly effective, temporary method of contraception 10 (See Chapter 18.). </td></tr><tr><td align="left" colspan="4" valign="top">Source: Trussell J. Contraceptive Efficacy. In Hatcher RA, Trussell J, Nelson AL, Cates W, Kowal D, Policar M. Contraceptive Techology: Twentieth Revised Edition. New York NY: Ardent Media, 2011.</td></tr></tfoot><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph> </paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>% of Women Experiencing an Unintended Pregnancy within the First Year of Use</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>% of Women Continuing Use at One Year</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Method </paragraph><paragraph>(1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Typical Use</paragraph><paragraph>(2)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Perfect Use</paragraph><paragraph>(3)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>(4)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>No method⁴</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>85</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>85</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Spermicides</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>42</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fertility awareness-based methods </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>24</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>47</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Standard Days method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> TwoDay method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Ovulation method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Symptothermal method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><t

Lrule Botrule " valign="top"><paragraph> Symptothermal method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><t r><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Withdrawal </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>46</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Sponge</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Parous women </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>20</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Nulliparous women </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Condom⁷</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Female (fc) </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>41</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Male </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>43</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diaphragm⁸</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>57</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Combined pill and progestin-only pill </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>67</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Norelgestromin and ethinyl estradiol pat

td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>67</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Norelgestromin and ethinyl estradiol pat ch </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>67</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>NuvaRing </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>67</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Depo-Provera </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>56</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Intrauterine contraceptives </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> ParaGard (copper T) </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>78</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Mirena (LNg) </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>80</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Implanon </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.05</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.05</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>84</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Female sterilization </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>100</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Male sterilization </paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.15</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragra

erilization </paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.15</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragra ph>100</paragraph></td></tr></tbody></table>

CONTRAINDICATIONS Progestin-only oral contraceptives (POPs) should not be used by women who currently have the following conditions: • Known or suspected pregnancy • Known or suspected carcinoma of the breast. • Undiagnosed abnormal genital bleeding • Hypersensitivity to any component of this product • Benign or malignant liver tumors • Acute liver disease

WARNINGS Cigarette smoking increases the risk of serious cardiovascular disease. Women who use oral contraceptives should be strongly advised not to smoke. Norethindrone tablets do not contain estrogen and, therefore, this insert does not discuss the serious health risks that have been associated with the estrogen component of combined oral contraceptives (COCs). The healthcare professional is referred to the prescribing information of combined oral contraceptives for a discussion of those risks. The relationship between progestin-only oral contraceptives and these risks is not fully defined. The healthcare professional should remain alert to the earliest manifestation of symptoms of any serious disease and discontinue oral contraceptive therapy when appropriate. 1. Ectopic Pregnancy The incidence of ectopic pregnancies for progestin-only oral contraceptive users is 5 per 1000 woman-years. Up to 10% of pregnancies reported in clinical studies of progestin-only oral contraceptive users are extrauterine. Although symptoms of ectopic pregnancy should be watched for, a history of ectopic pregnancy need not be considered a contraindication to use of this contraceptive method. Healthcare professionals should be alert to the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain while on progestin-only oral contraceptives. 2. Delayed Follicular Atresia/Ovarian Cysts If follicular development occurs, atresia of the follicle is sometimes delayed and the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally these enlarged follicles disappear spontaneously. Often they are asymptomatic; in some cases they are associated with mild abdominal pain. Rarely they may twist or rupture, requiring surgical intervention. 3. Irregular Genital Bleeding Irregular menstrual patterns are common among women using progestin-only oral contraceptives. If genital bleeding is suggestive of infection, malignancy or other abnormal conditions, such nonpharmacologic causes should be ruled out. If prolonged amenorrhea occurs, the possibility of pregnancy should be evaluated. 4. Carcinoma of the Breast and Reproductive Organs Some epidemiological studies of oral contraceptive users have reported an increased relative risk of developing breast cancer, particularly at a younger age and apparently related to duration of use. These studies have predominantly involved combined oral contraceptives and there is insufficient data to determine whether the use of POPs similarly increases the risk. A meta-analysis of 54 studies found a small increase in the frequency of having breast cancer diagnosed for women who were currently using combined oral contraceptives or had used them within the past ten years. This increase in the frequency of breast cancer diagnosis, within ten years of stopping use, was generally accounted for by cancers localized to the breast. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of use. Women with breast cancer should not use oral contraceptives because the role of female hormones in breast cancer has not been fully determined. Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women.

on of use. Women with breast cancer should not use oral contraceptives because the role of female hormones in breast cancer has not been fully determined. Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. There is insufficient data to determine whether the use of POPs increases the risk of developing cervical intraepithelial neoplasia. 5. Hepatic Neoplasia Benign hepatic adenomas are associated with combined oral contraceptive use, although the incidence of benign tumors is rare in the United States. Rupture of benign, hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in combined oral contraceptive users. However, these cancers are rare in the U.S. There is insufficient data to determine whether POPs increase the risk of developing hepatic neoplasia.

PRECAUTIONS 1. General Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. 2. Physical Examination and Follow up It is considered good medical practice for sexually active women using oral contraceptives to have annual history and physical examinations. The physical examination may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the healthcare professional. 3. Carbohydrate and Lipid Metabolism Some users may experience slight deterioration in glucose tolerance, with increases in plasma insulin but women with diabetes mellitus who use progestin-only oral contraceptives do not generally experience changes in their insulin requirements. Nonetheless, prediabetic and diabetic women in particular should be carefully monitored while taking POPs. Lipid metabolism is occasionally affected in that HDL, HDL2, and apolipoprotein A-I and A-II may be decreased; hepatic lipase may be increased. There is usually no effect on total cholesterol, HDL 3 , LDL, or VLDL. 4. Drug Interactions Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. • Effects of Other Drugs on Hormonal Contraceptives Substances decreasing the systemic concentrations of hormonal contraceptives (HCs) and potentially diminishing the efficacy of HCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the systemic concentrations of HCs and potentially diminish the effectiveness of HCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of HCs include efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between HCs and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative non-hormonal method of contraception or a back-up method when enzyme inducers are used with HCs, and to continue back-up non-hormonal contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Substances increasing the systemic concentrations of HCs: Co-administration of certain HCs and strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase the systemic concentrations of progestins, including norethindrone. Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) protease inhibitors and nonnucleoside reverse transcriptase inhibitors: Significant decreases in systemic concentrations of progestin have been noted in cases of co-administration with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine, efavirenz). In contrast, significant increases in systemic exposure of the progestin have been noted in cases of co-administration with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine).

s (e.g., nevirapine, efavirenz). In contrast, significant increases in systemic exposure of the progestin have been noted in cases of co-administration with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine). These changes may be clinically relevant in some cases. Consult the prescribing information of anti-viral and anti-retroviral concomitant medications to identify potential interactions. • Effects of Hormonal Contraceptives on Other Drugs Hormonal contraceptives may affect the metabolism of other drugs. Consequently, systemic concentrations may either increase (for example, cyclosporine) or decrease. Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. • Interactions between ulipristal and hormonal contraceptives Effectiveness of progestin-containing hormonal contraceptives and emergency contraceptive ulipristal acetate may be decreased if progestin-containing hormonal contraceptives are used within five days after ulipristal acetate dosing. Therefore, if a woman wishes to use norethindrone tablets after using ulipristal acetate, she should do so no sooner than 5 days after the intake of ulipristal acetate and she should use a reliable barrier method for subsequent acts of intercourse until her next menstrual period. 5. Interactions with Laboratory Tests The following endocrine tests may be affected by progestin-only oral contraceptive use: • Sex hormone-binding globulin (SHBG) concentrations may be decreased. • Thyroxine concentrations may be decreased, due to a decrease in thyroid binding globulin (TBG). 6. Carcinogenesis See WARNINGS . 7. Pregnancy Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. The few studies of infant growth and development that have been conducted have not demonstrated significant adverse effects. It is nonetheless prudent to rule out suspected pregnancy before initiating any hormonal contraceptive use. 8. Nursing Mothers In general, no adverse effects have been found on breastfeeding performance or on the health, growth, or development of the infant. However, isolated post-marketing cases of decreased milk production have been reported. Small amounts of progestins pass into the breast milk of nursing mothers, resulting in detectable steroid levels in infant plasma. 9. Pediatric Use Safety and efficacy of norethindrone tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated. 10. Fertility Following Discontinuation The limited available data indicate a rapid return of normal ovulation and fertility following discontinuation of progestin-only oral contraceptives. 11. Headache The onset or exacerbation of migraine or development of severe headache with focal neurological symptoms which is recurrent or persistent requires discontinuation of progestin-only contraceptives and evaluation of the cause. INFORMATION FOR THE PATIENT • See “Detailed Patient Labeling” for detailed information. • Counseling issues The following points should be discussed with prospective users before prescribing progestin-only oral contraceptives: • The necessity of taking pills at the same time every day, including throughout all bleeding episodes. • The need to use a backup method such as a condom and spermicide for the next 48 hours whenever a progestin-only oral contraceptive is taken 3 or more hours late.

fore prescribing progestin-only oral contraceptives: • The necessity of taking pills at the same time every day, including throughout all bleeding episodes. • The need to use a backup method such as a condom and spermicide for the next 48 hours whenever a progestin-only oral contraceptive is taken 3 or more hours late. • The potential side effects of progestin-only oral contraceptives, particularly menstrual irregularities. • The need to inform the healthcare professional of prolonged episodes of bleeding, amenorrhea or severe abdominal pain. • The importance of using a barrier method in addition to progestin-only oral contraceptives if a woman is at risk of contracting or transmitting STDs/HIV.

4. Drug Interactions Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. • Effects of Other Drugs on Hormonal Contraceptives Substances decreasing the systemic concentrations of hormonal contraceptives (HCs) and potentially diminishing the efficacy of HCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the systemic concentrations of HCs and potentially diminish the effectiveness of HCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of HCs include efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between HCs and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative non-hormonal method of contraception or a back-up method when enzyme inducers are used with HCs, and to continue back-up non-hormonal contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Substances increasing the systemic concentrations of HCs: Co-administration of certain HCs and strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase the systemic concentrations of progestins, including norethindrone. Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) protease inhibitors and nonnucleoside reverse transcriptase inhibitors: Significant decreases in systemic concentrations of progestin have been noted in cases of co-administration with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine, efavirenz). In contrast, significant increases in systemic exposure of the progestin have been noted in cases of co-administration with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine). These changes may be clinically relevant in some cases. Consult the prescribing information of anti-viral and anti-retroviral concomitant medications to identify potential interactions. • Effects of Hormonal Contraceptives on Other Drugs Hormonal contraceptives may affect the metabolism of other drugs. Consequently, systemic concentrations may either increase (for example, cyclosporine) or decrease. Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. • Interactions between ulipristal and hormonal contraceptives Effectiveness of progestin-containing hormonal contraceptives and emergency contraceptive ulipristal acetate may be decreased if progestin-containing hormonal contraceptives are used within five days after ulipristal acetate dosing.

l for enzyme alterations. • Interactions between ulipristal and hormonal contraceptives Effectiveness of progestin-containing hormonal contraceptives and emergency contraceptive ulipristal acetate may be decreased if progestin-containing hormonal contraceptives are used within five days after ulipristal acetate dosing. Therefore, if a woman wishes to use norethindrone tablets after using ulipristal acetate, she should do so no sooner than 5 days after the intake of ulipristal acetate and she should use a reliable barrier method for subsequent acts of intercourse until her next menstrual period.

7. Pregnancy Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. The few studies of infant growth and development that have been conducted have not demonstrated significant adverse effects. It is nonetheless prudent to rule out suspected pregnancy before initiating any hormonal contraceptive use.

8. Nursing Mothers In general, no adverse effects have been found on breastfeeding performance or on the health, growth, or development of the infant. However, isolated post-marketing cases of decreased milk production have been reported. Small amounts of progestins pass into the breast milk of nursing mothers, resulting in detectable steroid levels in infant plasma.

9. Pediatric Use Safety and efficacy of norethindrone tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

INFORMATION FOR THE PATIENT • See “Detailed Patient Labeling” for detailed information. • Counseling issues The following points should be discussed with prospective users before prescribing progestin-only oral contraceptives: • The necessity of taking pills at the same time every day, including throughout all bleeding episodes. • The need to use a backup method such as a condom and spermicide for the next 48 hours whenever a progestin-only oral contraceptive is taken 3 or more hours late. • The potential side effects of progestin-only oral contraceptives, particularly menstrual irregularities. • The need to inform the healthcare professional of prolonged episodes of bleeding, amenorrhea or severe abdominal pain. • The importance of using a barrier method in addition to progestin-only oral contraceptives if a woman is at risk of contracting or transmitting STDs/HIV.

ADVERSE REACTIONS Adverse reactions reported with the use of POPs include: • Menstrual irregularity is the most frequently reported side effect. • Frequent and irregular bleeding are common, while long duration of bleeding episodes and amenorrhea are less likely. • Headache, breast tenderness, nausea, and dizziness are increased among progestin-only oral contraceptive users in some studies. • Androgenic side effects such as acne, hirsutism, and weight gain occur rarely. The following adverse reactions were also reported in clinical trials or during post-marketing experience: Gastrointestinal Disorders: vomiting, abdominal pain; General Disorders and Administration Site Conditions: fatigue, edema; Psychiatric Disorders: depression, nervousness; Musculoskeletal and Connective Tissue Disorders : pain in extremity; Reproductive System and Breast Disorders: genital discharge; breast pain, menstruation delayed, suppressed lactation, vaginal hemorrhage, menorrhagia, withdrawal bleed when product is stopped; Immune System Disorders: anaphylactic/anaphylactoid reaction, hypersensitivity; Hepatobiliary Disorders: hepatitis, jaundice cholestatic; Skin and Subcutaneous Tissue Disorders: alopecia, rash, rash pruritic.

DOSAGE AND ADMINISTRATION To achieve maximum contraceptive effectiveness, norethindrone tablets must be taken exactly as directed. One tablet is taken every day, at the same time. Administration is continuous, with no interruption between pill packs. See Detailed Patient Labeling for detailed instruction.

HOW SUPPLIED Norethindrone tablets, USP 0.35 mg are available in cartons (NDC 68462-305-29) of 3 blisters (NDC 68462-305-84), each containing 28 light yellow to yellow round, flat faced, bevelled edged, uncoated tablets with ‘305’ debossed on one side and ‘G’ on the other side.

REFERENCES 1. McCann M, and Potter L. Progestin-Only Oral Contraceptives: A Comprehensive Review. Contraception, 50:60 (Suppl. 1), December 1994. 2. Van Giersbergen PLM, Halabi A, Dingemanse J. Pharmacokinetic interaction between bosentan and the oral contraceptives norethisterone and ethinyl estradiol. Int J Clin Pharmacol Ther 2006;44(3):113-118. 3. Truitt ST, Fraser A, Gallo ME, Lopez LM, Grimes DA and Schulz KF. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation (Review). The Cochrane Collaboration. 2007, Issue 3. 4. Halderman, LD and Nelson AL. Impact of early postpartum administration of progestin-only hormonal contraceptives compared with nonhormonal contraceptives on short-term breast feeding patterns. Am J Obstet Gynecol.; 186 (6): 1250-1258. 5. Ostrea EM, Mantaring III JB, Silvestre MA. Drugs that affect the fetus and newborn infant via the placenta or breast milk. Pediatr Clin N Am; 51 (2004): 539-579. 6. Cooke ID, Back DJ, Shroff NE: Norethisterone concentration in breast milk and infant and maternal plasma during ethynodiol diactetate administration. Contraception 1985; 31:611-21. 7. 2008 USPC Official:12/1/08-4/30/09, USP Monographs: Norethindrone Tablets (page 1 of 5) Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com July 2025 logo

DETAILED PATIENT LABELING Norethindrone Tablets, USP 0.35 mg This product (like all oral contraceptives) is used to prevent pregnancy. It does not protect against HIV infection (AIDS) or other sexually transmitted diseases. DESCRIPTION Norethindrone tablets, USP 0.35 mg Each tablet contains 0.35 mg norethindrone USP. Inactive ingredients include colloidal silicon dioxide, corn starch, D&C Yellow No. 10, ethyl cellulose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, methylene chloride, isopropyl alcohol and talc. INTRODUCTION This leaflet is about birth control pills that contain one hormone, a progestin. Please read this leaflet before you begin to take your pills. It is meant to be used along with talking with your healthcare professional. Progestin-only pills are often called “POPs” or “the minipill”. POPs have less progestin than the combined birth control pill (or “the pill”) which contains both an estrogen and a progestin. HOW EFFECTIVE ARE POPs? About 1 in 200 POP users will get pregnant in the first year if they all take POPs perfectly (that is, on time, every day). About 1 in 20 “typical” POP users (including women who are late taking pills or miss pills) gets pregnant in the first year of use. Table 2 will help you compare the efficacy of different methods. Table 2: Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year. United States. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year Method (1) Typical Use (2) Perfect Use (3) (4) No method 4 85 85 Spermicides 28 18 42 Fertility awareness-based methods 24 47 Standard Days method 6 5 TwoDay method 6 4 Ovulation method 6 3 Symptothermal method 6 0.4 Withdrawal 22 4 46 Sponge 36 Parous women 24 20 Nulliparous women 12 9 Condom 7 Female (fc) 21 5 41 Male 18 2 43 Diaphragm 8 12 6 57 Combined pill and progestin-only pill 9 0.3 67 Norelgestromin and ethinyl estradiol patch 9 0.3 67 NuvaRing 9 0.3 67 Depo-Provera 6 0.2 56 Intrauterine contraceptives ParaGard (copper T) 0.8 0.6 78 Mirena (LNg) 0.2 0.2 80 Implanon 0.05 0.05 84 Female sterilization 0.5 0.5 100 Male sterilization 0.15 0.10 100 Emergency Contraception: Emergency contraceptive pills or insertion of a copper intrauterine contraceptive after unprotected intercourse substantially reduces the risk of pregnancy. 9 (See Chapter 6.). Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraception.10 (See Chapter 18.) Source: Trussell J. Contraceptive Efficacy. In Hatcher RA, Trussell J, Nelson AL, Cates W, Kowal D, Policar M. Contraceptive Techology: Twentieth Revised Edition. New York NY: Ardent Media, 2011. Notes: 1. Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. Estimates of the probability of pregnancy during the first year of typical use for spermicides, withdrawal, fertility awareness-based methods, the diaphragm, the male condom, the oral contraceptive pill, and Depo-Provera are taken from the 1995 National Survey of Family Growth corrected for underreporting of abortion; see the text for the derivation of estimates for the other methods. 2.

ical use for spermicides, withdrawal, fertility awareness-based methods, the diaphragm, the male condom, the oral contraceptive pill, and Depo-Provera are taken from the 1995 National Survey of Family Growth corrected for underreporting of abortion; see the text for the derivation of estimates for the other methods. 2. Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. See the text for the derivation of the estimate for each method. 3. Among couples attempting to avoid pregnancy, the percentage who continue to use a method for 1 year. 4. The percentages becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within 1 year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within 1 year among women now relying on reversible methods of contraception if they abandoned contraception altogether. 5. Foams, creams, gels, vaginal suppositories, and vaginal film. 6. The Ovulation and TwoDay methods are based on evaluation of cervical mucus. The Standard Days method avoids intercourse on cycle days 8 through 19. The Symptothermal method is a double-check method based on evaluation of cervical mucus to determine the first fertile day and evaluation of cervical mucus and temperature to determine the last fertile day. 7. Without spermicides. 8. With spermicidal cream or jelly. 9. ella, Plan B One-Step and Next Choice are the only dedicated products specifically marketed for emergency contraception. The label for Plan B One-Step (one dose is 1 white pill) says to take the pill within 72 hours after unprotected intercourse. Research has shown that all of the brands listed here are effective when used within 120 hours after unprotected sex. The label for Next Choice (one dose is 1 peach pill) says to take 1 pill within 72 hours after unprotected intercourse and another pill 12 hours later. Research has shown that both pills can be taken at the same time with no decrease in efficacy or increase in side effects and that they are effective when used within 120 hours after unprotected sex. The FDA has in addition declared the following 19 brands of oral contraceptives to be safe and effective for emergency contraception: Ogestrel (1 dose is 2 white pills), Nordette (1 dose is 4 light-orange pills), Cryselle, Levora, Low-Ogestrel, Lo/Ovral, or Quasence (1 dose is 4 white pills), Jolessa, Portia, Seasonale or Trivora (1 dose is 4 pink pills), Seasonique (1 dose is 4 light-blue-green pills), Enpresse (one dose is 4 orange pills), Lessina (1 dose is 5 pink pills), Aviane or LoSeasonique (one dose is 5 orange pills), Lutera or Sronyx (one dose is 5 white pills), and Lybrel (one dose is 6 yellow pills). 10. However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age. Norethindrone tablets have not been studied for and are not indicated for use in emergency contraception. HOW DO POPs WORK?

another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age. Norethindrone tablets have not been studied for and are not indicated for use in emergency contraception. HOW DO POPs WORK? POPs can prevent pregnancy in different ways including: • They make the cervical mucus at the entrance to the womb (the uterus) too thick for the sperm to get through to the egg • They prevent ovulation (release of the egg from the ovary) in about half of the cycles • They also affect other hormones, the fallopian tubes and the lining of the uterus YOU SHOULD NOT TAKE POPs • If there is any chance you may be pregnant. • If you have breast cancer • If you have bleeding between your periods that has not been diagnosed • If you are hypersensitive, or allergic, to any component of this product. • If you have liver tumors, either benign or cancerous. • If you have acute liver disease. RISKS OF TAKING POPs Cigarette smoking greatly increases the possibility of suffering heart attacks and strokes. Women who use oral contraceptives are strongly advised not to smoke. WARNING: If you have sudden or severe pain in your lower abdomen or stomach area, you may have an ectopic pregnancy or an ovarian cyst. If this happens, you should contact your healthcare professional immediately. Ectopic Pregnancy An ectopic pregnancy is a pregnancy outside the womb. Because POPs protect against pregnancy, the chance of having a pregnancy outside the womb is very low. If you do get pregnant while taking POPs, you have a slightly higher chance that the pregnancy will be ectopic than do users of some other birth control methods. Ovarian Cysts These cysts are small sacs of fluid in the ovary. They are more common among POP users than among users of most other birth control methods. They usually disappear without treatment and rarely cause problems. Cancer of the Reproductive Organs and Breasts Some studies in women who use combined oral contraceptives that contain both estrogen and a progestin have reported an increase in the risk of developing breast cancer, particularly at a younger age and apparently related to duration of use. There is insufficient data to determine whether the use of POPs similarly increases this risk. A meta-analysis of 54 studies found a small increase in the frequency of having breast cancer diagnosed for women who were currently using combined oral contraceptives or had used them within the past ten years. This increase in the frequency of breast cancer diagnosis, within ten years of stopping use, was generally accounted for by cancers localized to the breast. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of use. Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives and there is insufficient data to determine whether the use of POPs increases the risk of developing cancer of the cervix. Liver Tumors In rare cases, combined oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, some studies report an increased risk of developing liver cancer among women who use combined oral contraceptives. However, liver cancers are rare. There is insufficient data to determine whether POPs increase the risk of liver tumors. Diabetic Women Diabetic women taking POPs do not generally require changes in the amount of insulin they are taking. However, your healthcare professional may monitor you more closely under these conditions.

liver cancers are rare. There is insufficient data to determine whether POPs increase the risk of liver tumors. Diabetic Women Diabetic women taking POPs do not generally require changes in the amount of insulin they are taking. However, your healthcare professional may monitor you more closely under these conditions. SEXUALLY TRANSMITTED DISEASES (STDs) WARNING: POPs do not protect against getting or giving someone HIV (AIDS) or any other STD, such as chlamydia, gonorrhea, genital warts or herpes SIDE EFFECTS Irregular Bleeding: The most common side effect of POPs is a change in menstrual bleeding. Your periods may be either early or late, and you may have some spotting between periods. Taking your pills late or missing pills can result in some spotting or bleeding. Other Side Effects Less common side effects include headaches, tender breasts, nausea, vomiting, dizziness, and fatigue. Depression, nervousness, leg pain, vaginal discharge, fluid retention, allergic reactions, jaundice or a yellowing of the skin or eyeballs, loss of scalp hair, rash/itchy rash, weight gain, acne and extra hair on your face and body have been reported, but are rare. If you are concerned about any of these side effects, check with your healthcare professional. USING POPs WITH OTHER MEDICINES Before taking a POP, inform your healthcare professional of any other medication, including over-the-counter medicine, that you may be taking. These medicines can make POPs less effective: Medicines for seizures such as: • Phenytoin • Carbamazepine • Phenobarbital • Felbamate • Oxcarbazepine • Rufinamide Medicine for nausea and vomiting caused by certain anti-cancer (chemotherapy) medicines: • (Fos)aprepitant Medicines for tuberculosis (TB): • Rifampin and rifabutin Medicine for fungal infections such as: • Griseofulvin Medicine for pulmonary hypertension such as: • Bosentan Medicines used for the treatment of HIV infections or AIDS and infections due to Hepatitis C such as: • Efavirenz, nevirapine, nelfinavir, and some ritonavir-containing drugs Herbal products such as: • St. John’s wort These medicines and substances can increase your exposure to POPs: Grapefruit juice Medicines for fungal infections such as: • Itraconazole • Voriconazole • Fluconazole • Ketoconazole Before you begin taking any new medicines be sure your healthcare professional knows you are taking a progestin-only birth control pill. HOW TO TAKE POPs IMPORTANT POINTS TO REMEMBER • POPs must be taken at the same time every day, so choose a time and then take the pill at that same time every day. Every time you take a pill late, and especially if you miss a pill, you are more likely to get pregnant. • Start the next pack the day after the last pack is finished. There is no break between packs. Always have your next pack of pills ready. • You may have some menstrual spotting between periods. Do not stop taking your pills if this happens. • If you vomit soon after taking a pill, use a backup method (such as a condom and/or a spermicide) for 48 hours. • If you want to stop taking POPs, you can do so at any time, but, if you remain sexually active and don’t wish to become pregnant, be certain to use another birth control method. • If you are not sure about how to take POPs, ask your healthcare professional. STARTING POPs • It’s best to take your first POP on the first day of your menstrual period. • If you decide to take your first POP on another day, use a backup method (such as a condom and/or a spermicide) every time you have sex during the next 48 hours. • If you have had a miscarriage or an abortion, you can start POPs the next day.

It’s best to take your first POP on the first day of your menstrual period. • If you decide to take your first POP on another day, use a backup method (such as a condom and/or a spermicide) every time you have sex during the next 48 hours. • If you have had a miscarriage or an abortion, you can start POPs the next day. IF YOU ARE LATE OR MISS TAKING YOUR POPs • If you are more than 3 hours late or you miss one or more POPs: • TAKE a missed pill as soon as you remember that you missed it, • THEN go back to taking POPs at your regular time, • BUT be sure to use a backup method (such as a condom and/or a spermicide) every time you have sex for the next 48 hours. • If you are not sure what to do about the pills you have missed, keep taking POPs and use a backup method until you can talk to your healthcare professional. IF YOU ARE BREASTFEEDING • If you are fully breastfeeding (not giving your baby any food or formula), you may start your pills 6 weeks after delivery. • If you are partially breastfeeding (giving your baby some food or formula), you should start taking pills by 3 weeks after delivery. IF YOU ARE SWITCHING PILLS • If you are switching from the combined pills to POPs, take the first POP the day after you finish the last active combined pill. Do not take any of the 7 inactive pills from the combined pill pack. You should know that many women have irregular periods after switching to POPs, but this is normal and to be expected. • If you are switching from POPs to the combined pills, take the first active combined pill on the first day of your period, even if your POPs pack is not finished. • If you switch to another brand of POPs, start the new brand anytime. • If you are breastfeeding, you can switch to another method of birth control at any time, except do not switch to the combined pills until you stop breastfeeding or at least until 6 months after delivery. PREGNANCY WHILE ON THE PILL If you think you are pregnant, contact your healthcare professional. Even though research has shown that POPs do not cause harm to the unborn baby, it is always best not to take any drugs or medicines that you don’t need when you are pregnant. You should get a pregnancy test: • If your period is late and you took one or more pills late or missed taking them and had sex without a backup method. • Anytime it has been more than 45 days since the beginning of your last period. WILL POPs AFFECT YOUR ABILITY TO GET PREGNANT LATER? If you want to become pregnant, simply stop taking POPs. POPs will not delay your ability to get pregnant. BREASTFEEDING If you are breastfeeding, POPs will not affect the quality or amount of your breast milk or the health of your nursing baby. However, isolated cases of decreased milk production have been reported. OVERDOSE No serious problems have been reported when many pills were taken by accident, even by a small child, so there is usually no reason to treat an overdose. OTHER QUESTIONS OR CONCERNS If you have any questions or concerns, check with your healthcare professional. You can also ask for the more detailed “Professional Labeling” written for doctors and other healthcare professionals. HOW TO STORE YOUR POPs Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep out of reach of children. Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com July 2025 logo1

<table ID="_RefID0EOXAE" width="100%"><caption>Table 2: Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year.

<table ID="_RefID0EOXAE" width="100%"><caption>Table 2: Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year. United States.</caption><col width="38%"/><col width="19%"/><col width="19%"/><col width="23%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph> </paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>% of Women Experiencing an Unintended Pregnancy within the First Year of Use</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>% of Women Continuing Use at One Year</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Method </paragraph><paragraph>(1)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Typical Use</paragraph><paragraph>(2)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Perfect Use</paragraph><paragraph>(3)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>(4)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>No method⁴</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>85</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>85</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Spermicides</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>42</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fertility awareness-based methods </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>24</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>47</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Standard Days method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> TwoDay method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Ovulation method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Symptothermal method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td styleCode="Rrule

" valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Symptothermal method⁶</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.4</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Withdrawal </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>46</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Sponge</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Parous women </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>20</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Nulliparous women </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Condom⁷</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Female (fc) </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>41</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Male </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>43</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diaphragm⁸</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>57</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Combined pill and progestin-only pill </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>67</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><para

rule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>67</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><para graph>Norelgestromin and ethinyl estradiol patch </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>67</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>NuvaRing </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>67</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Depo-Provera </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>56</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Intrauterine contraceptives </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> ParaGard (copper T) </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.6</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>78</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Mirena (LNg) </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>80</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Implanon </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.05</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.05</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>84</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Female sterilization </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>100</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Male sterilization </paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.15</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.10</paragraph></td><td align="center" styleCode="Rrule

rule Toprule " valign="top"><paragraph>Male sterilization </paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.15</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>100</paragraph></td></tr></tbody></table>