WARNINGS

Ethinyl estradiol; levonorgestrel are combination oral contraceptive (COC) pills. The following are the warnings given for daily cyclical combination oral contraceptive pill use (1 pill each day for 21 days of a 28-day cycle). It is not known whether these warnings also apply to the ECP regimen of four oral contraceptive pills taken within a 12-hour period.

Cardiovascular Disease (CVD)

COC use is associated with a small increase in the incidence of cardiovascular disease (CVD), primarily because of an increased risk of thrombosis rather than through an atherogenic mechanism. The degree of risk appears to be related primarily to the estrogen dosage. This increased risk is limited to the period during COC use and disappears upon cessation of use. Because the incidence of CVD is low during the reproductive years, the absolute risk attributable to COC use is quite small.

Deep Vein Thrombosis, Pulmonary Embolism

Use of COCs is associated with a low absolute risk of venous thromembolism which is nonetheless 3- to 6-fold higher than that among non-users. Smoking does not appear to be a risk factor.

The presence of factor V Leiden mutation and other hereditary coagulation disorders increases the risk of thromboembolic disease.

COC use is contraindicated for women who have deep vein thrombosis or pulmonary embolism and for those who have a history of these conditions.

Women who are immobilized for prolonged periods because of major surgery (or illness or injury) should not use COCs. For women undergoing major surgery without prolonged immobilization, the advantages of COC use generally outweigh the risk.

COC use should preferably not begin until two to three weeks postpartum, because of the risk of thrombosis.

Cerebrovascular Disease

In women who do not smoke and do not have hypertension, the risk of ischemic stroke in users of COCs is increased about 1.5 fold compared with non-users. The likelihood of hemorrhagic stroke is not increased among users of low-dose combined COCs who are under 35 years old and do not smoke or have hypertension. Women who have a history of stroke should not use COCs.

Ischemic Heart Disease

The likelihood of myocardial infarction is not increased among young women who use COCs and do not smoke or have hypertension or diabetes. Smokers older than 35 should not take COCs. Women who currently have ischemic heart disease, or who have a history of this disease, should not use COCs.

Valvular Heart Disease

COC use is contraindicated for women whose valvular heart disease is complicated by such factors as pulmonary hypertension, atrial fibrillation, or history of sub-acute bacterial encarditis. COC use may be acceptable for women with uncomplicated valvular heart disease.

Elevated Blood Pressure

For women with an elevation in blood pressure (160+/100+mmHg), COC use would present an unacceptable health risk, and COCs should not be used. Similarly, hypertensive women with vascular disease should not use COCs.

Ocular Lesions

There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions.

Carbohydrate Metabolism

For women with diabetes (both insulin-dependent and non-insulin dependent), who do not have vascular involvement, the advantages of COC use generally outweigh the risks, particularly the risks associated with pregnancy. The major concerns are vascular disease and added risk of thrombosis, although COC use by diabetic women appears to have only minimal effects on lipid metabolism and hemostasis. For diabetic women with nephropathy, retinopathy, neuropathy, or other vascular involvement, the risk-benefit ratio depends on the severity of the condition.

Headaches

For women with severe, recurrent headaches, including migraine headaches, the appropriateness of using COCs depends on the presence or absence of focal neurologic symptoms. These symptoms may reflect an increased risk of stroke and COC use is contraindicated in patients in whom they are present. The onset or exacerbation of migraines or the development of severe headache with focal neurological symptoms, which are recurrent or persistent, requires discontinuation of COC use and evaluation of the cause.

Unexplained Vaginal Bleeding

Women who have unexplained vaginal bleeding, suggestive of an underlying pathological condition or pregnancy, should be evaluated prior to initiation of COC use in order to avoid confusion of the pathological bleeding with COC side effects.

Liver Disease

Because steroid hormones are metabolized by the liver, women taking COCs may experience adverse hepatobiliary effects. Although case-control studies have indicated that the risk of both benign and malignant liver tumors may be slightly increased by COC use, the incidence potentially attributable to COCs in the United States is minimal because the disease is very rare.

Women who currently have active liver disease should not use COCs.

Ectopic Pregnancy

Ectopic as well as intrauterine pregnancy may occur in contraceptive failures.

PRECAUTIONS

Sexually Transmitted Diseases: Women should be informed that this product does not protect against infection with HIV (the virus that causes AIDS) and other sexually transmitted diseases (STDs). If a woman is at high risk for STDs she should be encouraged to reduce risky behavior and to use condoms or other barrier methods (in addition to COCs).

Pregnancy: Extensive research has found no significant effects on fetal development associated with long-term use of contraceptive doses of oral steroids before pregnancy or taken inadvertently during early pregnancy.

Nursing Mothers: Oral contraceptive steroids have been reported in the milk of breastfeeding mothers with no apparent clinical significance; long-term follow-up of breastfeeding mothers with no apparent clinical significance; long-term follow-up of children whose mothers used COCs while breastfeeding has shown no deleterious effects.

Pediatric Use: The safety and efficacy of COCs have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under 16 and users 16 and older. Use of this product before menarche is not indicated.

Repeated Use of Emergency Contraceptive Pills: The effect of repeated use of ECPs (more than once in a menstrual cycle or in multiple cycles) is unknown.

See PATIENT PACKAGE INSERT Information for the Patient.