Norethindrone acetate 5 mg Tablet, 50-count — NDC 50742-267-50 (Billing 50742-0267-50)

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.

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, please call Ingenus Pharmaceuticals, LLC toll-free at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

3 Drug/Laboratory Tests 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 radio immunoassay) or T 3 levels by radio immunoassay. 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.

PRECAUTIONS 1 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 2 Information for the Patient Healthcare providers are advised to discuss the PATIENT INFORMATION leaflet with patients for whom they prescribe norethindrone acetate tablets.

3 Drug/Laboratory Tests 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 radio immunoassay) or T 3 levels by radio immunoassay. 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. 4 Carcinogenesis, Mutagenesis, and 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. 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. 7 Pediatric Use Norethindrone acetate tablets ar… [Excerpted — this section continues on DailyMed.]