An increased risk of the following adverse reactions has been reported with the use of progestin-only oral contraceptives (POCs) such as norethindrone POC: menstrual irregularity, changes in menstrual flow, breakthrough bleeding or spotting, dysmenorrhea, amenorrhea, or prolonged menstrual-like bleeding. Irregular menstrual patterns are the most common side effect among users of POCs and are usually described as vaginal bleeding which, in the judgment of the subject, does not have the characteristics of pre-treatment menstrual periods in duration, amount or appearance. Breakthrough bleeding and spotting are most commonly reported for these events. A long duration of bleeding episodes and amenorrhea are less likely. The following adverse reactions were also reported in clinical trials or during postmarketing experience with POCs: delayed menstruation, vaginal hemorrhage, menorrhagia, withdrawal bleed when the POC is stopped. If uterine vaginal bleeding together with the clinical history is suggestive of infection, malignancy, pregnancy, or other conditions, rule out these conditions. If amenorrhea occurs, consider the possibility of pregnancy. During POC use, atresia of the follicle is sometimes delayed after follicle development (if it occurs), and the follicle may continue to grow beyond the size it would attain in a normal cycle and become an ovarian cyst. Generally, an ovarian cyst will disappear spontaneously. Often they are asymptomatic; in some cases they are associated with pain, and rarely these may twist or rupture, requiring surgical intervention.[57588] HORMONAL THERAPY (norethindrone acetate): The following menstrual-related side effects have been reported in women taking progestins: breakthrough bleeding or spotting, changes in menstrual flow, and amenorrhea. In cases of breakthrough bleeding, and in all cases of irregular vaginal bleeding, nonfunctional causes should be borne in mind. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures are indicated.[48333]

Breast tenderness has been reported to be increased with the use of progestin-only oral contraceptives (POCs) in some studies. The following additional adverse reactions were reported by individuals taking POCs such as norethindrone in clinical trials or during postmarketing experience: genital or vaginal discharge; breast pain (mastalgia), and lactation suppression.[57588] HORMONE THERAPY (norethindrone acetate): Progestins have been reported to cause changes in the cervical secretions (leukorrhea) and breast enlargement/tenderness in women.[48333]

Headache and dizziness are increased among progestin-only contraceptive (POC) users in some studies. The onset or exacerbation of migraine or development of severe headache with focal neurological symptoms which is recurrent or persistent requires discontinuation of the POC and evaluation of the cause.[57588] Although findings on the risk for venous thromboembolism with use of POCs in otherwise healthy users is inconsistent, any small increased risk for thromboembolism is substantially less than that with combined oral contraceptive agents. POC recipients do not appear to have an increased risk for ischemic strokes compared with nonusers.[48201] HORMONAL THERAPY (norethindrone acetate): Thrombotic and thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, retinal thrombosis, and cerebral thrombosis, embolism and stroke) have been reported in women treated with progestins.[48333]

The following general adverse reactions were reported in clinical trials or during postmarketing experience with progestin-only contraceptives (POCs): fatigue, edema, and/or fluid retention.[57588] HORMONAL THERAPY (norethindrone acetate): Edema has been reported in women taking progestins.

Androgenic side effects of progestin-only oral contraceptives (POCs), such as acne vulgaris, hirsutism, and weight gain occur rarely. The following dermatologic and allergic adverse reactions were also reported in clinical trials or during postmarketing experience with POCs: anaphylactic/anaphylactoid reactions, hypersensitivity, alopecia, rash, and pruritic rash.[57588] HORMONAL THERAPY (norethindrone acetate): The following have been reported in women taking progestins: changes in weight (decreases, increases), rash (allergic) with and without pruritus, melasma or chloasma, acne, urticaria, and anaphylactic/anaphylactoid reactions.[48333]

Nausea is increased among progestin-only oral contraceptive (POC) users in some studies. The following adverse reactions were also reported in clinical trials or during postmarketing experience with POC use: vomiting and abdominal pain.[57588] HORMONAL THERAPY (norethindrone acetate): Nausea has been reported in women taking progestins.[48333]

The following hepatobiliary adverse reactions were reported in clinical trials or during postmarketing experience with progestin-only oral contraceptives (POCs): hepatitis, cholestatic jaundice, and/or elevated hepatic enzymes. Cholestasis has also been rarely reported. Discontinue the POC if jaundice or acute disturbances of liver function develop. Do not resume use until markers of liver function return to normal and drug causation has been excluded.[57588] HORMONAL THERAPY (norethindrone acetate): Cholestatic jaundice and abnormalities of liver tests (i.e., increased AST, ALT, and hyperbilirubinemia) have been reported in women taking progestins.[48333]

The following psychiatric adverse reactions were reported in clinical trials or during postmarketing experience with progestin-only oral contraceptives (POCs): depression and nervousness.[57588] HORMONAL THERAPY (norethindrone acetate): clinical depression, mood swings (emotional lability), and insomnia have been reported in women taking progestins.[48333]

Be alert to the possibility of an ectopic pregnancy in people who become pregnant or complain of lower abdominal pain while taking norethindrone contraceptive tablets. Users of progestin-only oral contraceptives (POCs) have a higher absolute rate of ectopic pregnancy than do users of other types of progestin-only contraceptives, but the incidence is still lower than in individuals using no contraceptive method. The incidence of ectopic pregnancies for POC users is 5 per 1,000 woman-years. Up to 10% of pregnancies reported in clinical studies of POCs were extrauterine.[57588] [48201]

HORMONAL THERAPY (norethindrone acetate): Optic neuritis (which may lead to partial or complete loss of vision) has been reported in women treated with progestins.[48333]

Norethindrone oral contraceptive use does not protect against human immunodeficiency virus (HIV) infection or other sexually transmitted disease. Conversely, patients with known HIV infection or acquired immunodeficiency syndrome (AIDS) should be aware that the use of hormonal oral contraceptives will not prevent the transmission of HIV or other diseases to their partner(s).[57588]

Norethindrone oral contraceptive use is considered contraindicated in those with acute hepatic disease.[57588] In general, however, experts consider progestin-only oral contraceptives to be acceptable for use in most patients with liver disease.[48201] [70437] Norethindrone contraception is contraindicated in patients with benign or malignant liver tumors (e.g., hepatic adenomas or hepatocellular cancer). Benign hepatic adenomas are associated with combined oral contraceptive use, although the incidence of benign tumors is rare in the U.S. 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 progestin-only oral contraceptives increase the risk of developing hepatic neoplasia.[57588] HORMONAL THERAPY (norethindrone acetate): Norethindrone acetate is contraindicated for use in people with impaired liver function or hepatic disease.[48333]

Norethindrone contraception is contraindicated in people with known or suspected carcinoma of the breast. Individuals with breast cancer should not use hormonal oral contraceptives because the role of female hormones in breast cancer has not been fully determined.[57588] HORMONAL THERAPY (norethindrone acetate): Individuals with known, suspected or history of cancer of the breast are contraindicated to receive norethindrone acetate.[48333]

Norethindrone contraception is contraindicated for use in those with undiagnosed abnormal vaginal bleeding; patients with this condition should be evaluated by a qualified health care professional before norethindrone contraceptive use. If uterine bleeding together with the clinical history is suggestive of infection, malignancy, being pregnant, or other conditions, rule out these conditions. Menstrual irregularity is common among individuals using progestin-only oral contraception and amenorrhea may occur. Delayed follicular atresia sometimes occurs if a follicle develops during a cycle, and it may enlarge and become an ovarian cyst. Generally, these disappear spontaneously. Often they are asymptomatic; in some cases they are associated with mild abdominal pain, and rarely they may twist or rupture, requiring surgical intervention.[57588] HORMONAL THERAPY (norethindrone acetate): Contraindicated for use in people with undiagnosed vaginal bleeding. In cases of breakthrough bleeding, and in all cases of irregular bleeding per vagina, nonfunctional causes should be considered. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures are indicated.[48333]

Norethindrone contraception is contraindicated for use during pregnancy or suspected pregnancy, because there is no reason to use hormonal contraceptives during 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 prudent, however, to rule out suspected pregnancy before initiating any hormonal contraceptive use, including norethindrone.[57588] HORMONAL THERAPY (norethindrone acetate): Norethindrone acetate is contraindicated for use during pregnancy or suspected pregnancy. There is no known indication of norethindrone acetate use during pregnancy, and these products are contraindicated for use as a diagnostic test for pregnancy. Norethindrone acetate may cause fetal harm when administered during pregnancy. 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.[48333]

Be alert to the possibility of an ectopic pregnancy in individuals who become pregnant or who complain of lower abdominal pain while taking norethindrone oral contraception. The incidence of ectopic pregnancy during use of progestin-only oral contraceptives is 5 per 1,000 woman-years and up to 10% of pregnancies reported in progestin-only oral contraceptive users are extrauterine.[57588]

Progestin-only oral contraceptives (POCs), including norethindrone, are considered compatible with breast-feeding; available evidence suggests that POCs are preferable to other hormonal contraceptives during lactation. Small amounts of progestin pass into the breast milk, resulting in steroid levels in infant plasma. In general, no adverse effects on breast-feeding performance or on the health, growth, or development of the infant have occurred with POCs. Only rarely have there been isolated reports of decreased lactation during POC use; monitoring of infant weight gain and growth can occur as per usual practices.[57588] [48335] [48201] Alternate contraceptive agents to consider for the breast-feeding individual include non-hormonal contraceptive methods (e.g., copper IUD, barrier methods) and other progestin-only contraceptives (e.g., medroxyprogesterone contraceptive injections, norgestrel oral contraceptive, levonorgestrel IUDs).[48201] HORMONAL THERAPY (norethindrone acetate): Use norethindrone acetate with caution during breast-feeding.; progestins pass into breast milk in low amounts, resulting in steroid levels in infant plasma of 1% to 6% of the levels of maternal plasma.[48333]

Tobacco smoking increases the risk of serious cardiovascular disease; individuals taking norethindrone contraception should be strongly advised not to smoke.[57588] HORMONAL THERAPY (norethindrone acetate): Norethindrone acetate is contraindicated in people with active deep venous thromboembolism or thrombosis, pulmonary embolism, or a history of these conditions. The drug is also contraindicated in those with active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction). People with risk factors for arterial vascular disease (e.g., hypertension, diabetes, tobacco smoking, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.[48333]

The effect of progestin-only oral contraceptives on carbohydrate and lipid metabolism is generally not clinically significant, but some individuals may experience slight deterioration in glucose tolerance. People with prediabetes or diabetes mellitus should be carefully monitored while taking progestin-only contraception. 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, HDL3, LDL, or VLDL.[57588] HORMONAL THERAPY (norethindrone acetate): 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. People with hyperlipidemia and/or diabetes mellitus should be monitored closely during progestin therapy.[48333]

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 such as norethindrone contraception and evaluation of the cause.[57588] HORMONAL THERAPY (norethindrone acetate): Discontinue norethindrone acetate pending examination if there is a visual impairment such as 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, norethindrone acetate should be discontinued.[48333]

HORMONAL THERAPY (norethindrone acetate): Because norethindrone acetate may cause some degree of fluid retention, conditions which might be influenced by this factor, such as cardiac disease, renal disease, and seizure disorder/epilepsy require careful observation.[48333]

HORMONAL THERAPY (norethindrone acetate): Patients who have a history of clinical depression should be carefully observed, and the drug discontinued if the depression recurs to a serious degree.[48333]