Norethindrone Acetate And Ethinyl Estradiol

Description

11 DESCRIPTION Jinteli ® (norethindrone acetate and ethinyl estradiol tablets, USP) are a continuous dosage regimen of a progestin-estrogen combination for oral administration. Each white tablet contains 1 mg norethindrone acetate, USP [19-Norpregn-4-en-20-yn-3-one,7(acetyloxy)-, (17α)-] and 5 mcg ethinyl estradiol, USP [19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17α)-]. Each tablet also contains the following inactive ingredients: calcium stearate, lactose monohydrate, microcrystalline cellulose, pregelatinized corn starch, and sodium starch glycolate. The structural formulas are as follows: Norethindrone Acetate, USP Ethinyl Estradiol, USP C 22 H 28 O 3 M.W. 340.46 C 20 H 24 O 2 M.W. 296.40 new

What Is Norethindrone Acetate And Ethinyl Estradiol Used For?

1 INDICATIONS AND USAGE Jinteli is a combination of an estrogen and progestin indicated in a woman with a uterus for: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) Prevention of Postmenopausal Osteoporosis ( 1.2 ) 1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause 1.2 Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Use estrogen, alone or in combination with a progestogen, at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman. Re-evaluate postmenopausal women periodically as clinically appropriate to determine whether treatment is still necessary. One tablet orally once daily ( 2.1 , 2.2 ) 2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Take a single Jinteli, 1 mg/5 mcg, orally once daily. 2.2 Prevention of Postmenopausal Osteoporosis Take a single Jinteli tablet 1 mg/5 mcg, orally once daily.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions ( 5.1 )] . Malignant Neoplasms [see Boxed Warning, Warnings and Precautions ( 5.2 )] . The most common adverse reactions with Jinteli (incidence greater than or equal to 5 percent) are: headache, abdominal pain, breast pain, and edema (generalized) ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions reported by ≥ 5 percent of women in controlled clinical studies of Jinteli are shown in Table 1. Table 1. Associated Adverse Reactions Reported by ≥ 5 Percent of Women by Body System* BODY SYSTEM/ Adverse Reaction Number (Percent) of Subjects Placebo Jinteli 0.5/2.5 Jinteli 1/5 N = 247 N = 244 N = 258 BODY AS A WHOLE 23 (12.8) 30 (16.9) 30 (15.7) Edema - Generalized 10 (4.0) 12 (4.9) 11 (4.3) Headache 12 (4.9) 14 (5.7) 16 (6.2) DIGESTIVE SYSTEM 8 (4.4) 17 (9.6) 25 (13.1) Abdominal Pain 3 (1.2) 13 (5.3) 14 (6.8) UROGENITAL SYSTEM 20 (11.1) 34 (19.2) 45 (23.6) Breast Pain 9 (3.6) 22 (9.0) 20 (7.8) * The total number of women for each body system may be less than the number of women with AEs in that body system because a woman may have had more than one AE per body system 6.2 Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of Jinteli. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Genitourinary System Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; increase in size of uterine leiomyomata, vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer; uterine cancer; vaginal hemorrhage; ovarian cyst; irregular menstruation; metrorrhagia; menorrhagia; dysmenorrhea; uterine enlargement. Breasts Tenderness, enlargement, breast pain, nipple pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer; breast disorder; breast mass; breast enlargement. Cardiovascular Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; thrombosis; chest pain; myocardial infarction; cerebrovascular accident (stroke); transient ischemic attack; hemiparesis; increase in blood pressure; irregular heart rate; palpitations; dyspnea. Gastrointestinal Nausea, vomiting; cholestatic jaundice; pancreatitis, enlargement of hepatic hemangiomas; bloating, abdominal cramps; abdominal pain; increased incidence of gallbladder disease; cholecystitis; cholelithiasis. Skin Chloasma or melasma that may persist when drug is discontinued; generalized erythema; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; rash, pruritus. Eyes Retinal vascular thrombosis; visual impairment; intolerance to contact lenses. Central Nervous System (CNS) Headache; migraine; dizziness; depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia; paresthesia; insomnia. Miscellaneous Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgias; leg cramps; back pain; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides; blood glucose abnormal; fatigue; myalgia; hypersensitivity.

Drug Interactions

7 DRUG INTERACTIONS In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen and progestin drug metabolism. Inducers of CYP3A4 such as St. John’s wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine and rifampin may decrease the plasma concentration of estrogens and progestins, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase the plasma concentration of the estrogen or the progestin or both and may result in adverse reactions. Coadministration of atorvastatin and certain hormonal products containing ethinyl estradiol increase AUC values for ethinyl estradiol approximately 20 percent. Ascorbic acid and acetaminophen may increase the plasma ethinyl estradiol concentration, possibly by inhibition of conjugation. Combination hormonal products have been shown to significantly decrease the plasma concentration of lamotrigine likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. ( 7 )

Contraindications

4 CONTRAINDICATIONS Jinteli is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding [see Warnings and Precautions ( 5.2 )]. Breast cancer or a history of breast cancer [see Warnings and Pr ecautions ( 5.2 )]. Estrogen-dependent neoplasia [see Warnings and Precautions ( 5.2 )]. Active DVT, PE or a history of these conditions [see Warnings and Precautions ( 5.1 )]. Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions [see Warnings and Precautions ( 5.1 )]. Known anaphylactic reaction, angioedema, or hypersensitivity to Jinteli Hepatic impairment or disease. Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Undiagnosed abnormal genital bleeding ( 4 , 5.2 ) Breast cancer or a history of breast cancer ( 4 , 5.2 ) Estrogen-dependent neoplasia ( 4 , 5.2 ) Active DVT, PE, or history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions ( 4 , 5.1 ) Known anaphylactic reaction, angioedema, or hypersensitivity to Jinteli ( 4 ) Hepatic impairment or disease ( 4 , 5.10 ) Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Jinteli is not indicated for use in pregnancy. There are no data with the use of Jinteli in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined (estrogens and progestins) product before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

8.2 Lactation Risk Summary Estrogens plus progestogens are present in human milk and can reduce milk production in breastfeeding women. This reduction can occur at any time but is less likely to occur once breastfeeding is well-established. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Jinteli and any potential adverse effects on the breastfed child from Jinteli or from the underlying maternal condition.

Overdosage

10 OVERDOSAGE Overdosage of estrogen plus progestogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of Jinteli therapy with institution of appropriate symptomatic care.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Jinteli ® (norethindrone acetate and ethinyl estradiol tablets, USP) is available in the following strength and package sizes: 1 mg/5 mcg - White, round, flat-faced, beveled-edge, unscored tablets, debossed with stylized b on one side and 125 on the other side. Bottle of 90 tablets (NDC 0093- 3122 -98) 5 Blister Cards of 28 tablets per carton (NDC 0093- 3122 -42) 16.2 Storage and Handling Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep this and all medications out of the reach of children.