Nora BE Norethindrone .35 mg Tablet, 168-count — NDC 52544-629-28 (Billing 52544-0629-28)

WARNINGS Cigarette smoking greatly increases the possibility of suffering heart attacks and strokes. Women who use oral contraceptives are strongly advised not to smoke. Nora-BE does 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.

The health care provider is referred to the prescribing information of combined oral contraceptives for a discussion of those risks, including, but not limited to, an increased risk of serious cardiovascular disease in women who smoke, carcinoma of the breast and reproductive organs, hepatic neoplasia, and changes in carbohydrate and lipid metabolism. The relationship between progestin-only oral contraceptives and these risks have not been established and there are no studies definitely linking progestin-only pill (POP) use to an increased risk of heart attack or stroke.

The physician 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.

Health providers 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 epidemiologic 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 increase the risk. Women with breast cancer should not use oral contraceptives because the role of female hormone 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 intraabdominal hemorrhage.

Studies from Britain and the U.S. have shown an increased risk of developing hepatocellular carcinoma in combined oral contraceptive users. However, these cancers are rare. There is insufficient data to determine whether POPs increase the risk of developing h… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS 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.

4. Drug interactions. Change in contraceptive effectiveness associated with co-administration of other products: a.

Anti-infective agents and anticonvulsants. Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding.

Examples include rifampin, barbiturates, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate, and griseofulvin. b. Anti-HIV protease inhibitors. Several of the anti-HIV protease inhibitors have been studied with co-administration of oral contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases.

The safety and efficacy of OC products may be affected with the co-administration of anti-HIV protease inhibitors. Health care providers should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information. c. Herbal products.

Herbal products containing St. John's Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.

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).

PRECAUTIONS 1. General. Patients should be counseled that oral contraceptives do not protect against transmission of HIV (AIDS) and other sexually transmitted diseases (STDs) such as Chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.

2. Physical examination and followup. 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 clinician. 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, HDL 2 , and apolipoprotein A-I and A-II may be decreased; hepatic lipase may be increased.

There is no effect on total cholesterol, HDL 3 , LDL, or VLDL. 4. Drug interactions.

Change in contraceptive effectiveness associated with co-administration of other products: a. Anti-infective agents and anticonvulsants. Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids.

This could result in unintended pregnancy or breakthrough bleeding. Examples include rifampin, barbiturates, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate, and griseofulvin. b. Anti-HIV protease inhibitors.

Several of the anti-HIV protease inhibitors have been studied with co-administration of oral contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases. The safety and efficacy of OC products may be affected with the co-administration of anti-HIV protease inhibitors. Health care providers should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information. c.

Herbal products. Herbal products containing St. John's Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids.

This may also result in breakthrough bleeding. 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 section. 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.

Small amounts of progestin pass into the breast milk, resulting in steroid levels in infant plasma of 1-6% of the levels of maternal plasma. 6 However, isolated post-market cases of decreased milk production have been reported in POPs. Very rarely, adverse effects in the infant/child have been reported, including jaundice.

9. Fertility following discontinuation. The limited available data indicate a rapid return of normal ovulation and fertility following discontinuation of progestin-only oral contraceptives.

10. Headache/Migraine. If you have a headache or a worsening migraine headache with a new pattern that is recurrent, persistent, or severe, this requires discontinuation of oral contraceptives and eval… [Excerpted — this section continues on DailyMed.]