Levonest levonorgestrel and ethinyl estradiol Kit, 1 kit — NDC 50090-2505-0 (Billing 50090-2505-00)

WARNINGS The use of oral contraceptives is associated with increased risks of several serious conditions including venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, and stroke), hepatic neoplasia, gallbladder disease, and hypertension, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as certain inherited or acquired thrombophilias, hypertension, hyperlipidemias, obesity, and diabetes.

Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is based principally on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined.

Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of disease, namely, a ratio of the incidence of a disease among oral-contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease.

Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral-contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population. For further information, the reader is referred to a text on epidemiological methods.

1. Thromboembolic Disorders And Other Vascular Problems a. Myocardial infarction An increased risk of myocardial infarction has been attributed to oral-contraceptive use.

This risk is primarily in smokers or women with other underlying risk factors for coronary-artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral-contraceptive users has been estimated to be two to six. The risk is very low under the age of 30.

Smoking in combination with oral-contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Table III) among women who use oral contraceptives. Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age, and obesity.

In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users (see section 9 in " WARNINGS " ). Similar effects on risk factors have been associated with an increased risk of heart disease.

Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. b. Thromboembolism An increased risk of venous thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to nonusers to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep-vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease.

Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. T… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC. Toll-Free at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . An increased risk of the following serious adverse reactions (see " WARNINGS " section for additional information) has been associated with the use of oral contraceptives.

Thromboembolic disorders and other vascular problems (including thrombophlebitis, arterial thromboembolism, pulmonary embolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis), carcinoma of the reproductive organs, hepatic neoplasia (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache. The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug related: Nausea.

Vomiting. Gastrointestinal symptoms (such as abdominal pain, cramps and bloating). Breakthrough bleeding.

Spotting. Change in menstrual flow. Amenorrhea.

Temporary infertility after discontinuation of treatment. Edema/fluid retention. Melasma/chloasma which may persist.

Breast changes: tenderness, pain, enlargement, secretion. Change in weight or appetite (increase or decrease). Change in cervical erosion and secretion.

Diminution in lactation when given immediately postpartum. Cholestatic jaundice. Rash (allergic).

Mood changes, including depression. Vaginitis, including candidiasis. Change in corneal curvature (steepening).

Intolerance to contact lenses. Mesenteric thrombosis. Decrease in serum folate levels.

Exacerbation of systemic lupus erythematosus. Exacerbation of porphyria. Exacerbation of chorea.

Aggravation of varicose veins. Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms. The following adverse reactions have been reported in users of oral contraceptives, and the association has been neither confirmed nor refuted: Congenital anomalies.

Premenstrual syndrome. Cataracts. Optic neuritis, which may lead to partial or complete loss of vision.

Cystitis-like syndrome. Nervousness. Dizziness.

Hirsutism. Loss of scalp hair. Erythema multiforme.

Erythema nodosum. Hemorrhagic eruption. Impaired renal function.

Hemolytic uremic syndrome. Budd-Chiari syndrome. Acne.

Changes in libido. Colitis. Sickle-cell disease.

Cerebral-vascular disease with mitral valve prolapse. Lupus-like syndromes. Pancreatitis.

Dysmenorrhea.

PRECAUTIONS 1. General Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. This product contains FD&C Yellow No.

5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

2. Physical Examination And Follow-Up A periodic personal and family medical history and complete physical examination are appropriate for all women, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician.

The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.

3. Lipid Disorders Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult.

(See " WARNINGS " 1d . ) In patients with familial defects of lipoprotein metabolism receiving estrogen-containing preparations, there have been case reports of significant elevations of plasma triglycerides leading to pancreatitis. 4. Liver Function If jaundice develops in any woman receiving such drugs, the medication should be discontinued.

Steroid hormones may be poorly metabolized in patients with impaired liver function. 5. Fluid Retention Oral contraceptives may cause some degree of fluid retention.

They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. 6. Emotional Disorders Patients becoming significantly depressed while taking oral contraceptives should stop the medication and use an alternate method of contraception in an attempt to determine whether the symptom is drug related.

Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. 7. Contact Lenses Contact-lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

8. Gastrointestinal Motility Diarrhea and/or vomiting may reduce hormone absorption. 9.

Drug Interactions Interactions between ethinyl estradiol and other substances may lead to decreased or increased serum ethinyl estradiol concentrations. Decreased ethinyl estradiol plasma concentrations may cause an increased incidence of breakthrough bleeding and menstrual irregularities and may possibly reduce efficacy of the combination oral contraceptive. Reduced ethinyl estradiol concentrations have been associated with concomitant use of substances that induce hepatic microsomal enzymes, such as rifampin, rifabutin, barbiturates, phenylbutazone, phenytoin sodium, griseofulvin, topiramate, some protease inhibitors, modafinil, and possibly St.

John's wort. Substances that may decrease plasma ethinyl estradiol concentrations by other mechanisms include any substance that reduces gut transit time and certain antibiotics (e.g. ampicillin and other penicillins, tetracyclines) by a decrease of enterohepatic circulation of estrogens. During concomitant use of ethinyl estradiol containing products and substances that may lead to decreased plasma steroid hormone concentrations, it is recommended that a nonhormonal back-up method of birth control be used in addition to the regular intake of LEVONEST™ (levono… [Excerpted — this section continues on DailyMed.]