Norethindrone Acetate

INDICATIONS AND USAGE Norethindrone acetate 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 is not intended, recommended or approved to be used with concomitant estrogen therapy in postmenopausal women for endometrial protection.

DOSAGE AND ADMINISTRATION Therapy with norethindrone acetate 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 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 therapy. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with norethindrone acetate. Endometriosis: Initial daily dosage of 5 mg norethindrone acetate for two weeks. Dosage should be increased by 2.5 mg per day every two weeks until 15 mg per day of norethindrone acetate is reached. Therapy may be held at this level for six to nine months or until annoying breakthrough bleeding demands temporary termination.

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.

CONTRAINDICATIONS • Known or suspected pregnancy. There is no indication for norethindrone acetate 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

5. 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.

6. 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.

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)