amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease A decline in serum high-density lipoproteins (HDL) has been reported with many progestational agents; a decline in serum high-density lipoproteins has been associated with an increased incidence of ischemic heart disease; 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 control of hyperlipidemias more difficult; nonhormonal contraception should be considered in women with uncontrolled dyslipidemias; persistent hypertriglyceridemia may occur; elevations of plasma triglycerides may lead to pancreatitis and other complications Diarrhea and/or vomiting may reduce hormone absorption resulting in decreased serum concentrations Increase in blood pressure reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use; women with history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception; if women with hypertension elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued Onset or exacerbation of migraine or development of headache with new pattern that is recurrent, persistent, or severe requires discontinuation of oral contraceptives and evaluation of the cause The convenience of having no scheduled menstrual bleeding should be weighed against the inconvenience of unscheduled breakthrough bleeding and spotting Ectopic as well as intrauterine pregnancy may occur in contraceptive failures Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care For women with well-controlled hypertension, monitor blood pressure and stop treatment if blood pressure rises significantly Studies suggest a small increased relative risk of developing gallbladder disease among COC users; use of COCs may worsen existing gallbladder disease; a past history of COC-related cholestasis predicts an increased risk with subsequent COC use; women with a history of pregnancy-related cholestasis may be at increased risk for COC related cholestasis If a woman receiving therapy develops new headaches that are recurrent, persistent, or severe, evaluate cause and discontinue therapy if indicated; consider discontinuation in case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) If bleeding persists or occurs after previously regular cycles, check for causes such as pregnancy or malignancy; if pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different contraceptive product Women receiving therapy may experience amenorrhea, absence of withdrawal bleeding, even if they are not pregnant; if scheduled (withdrawal) bleeding does not occur, consider possibility of pregnancy if patient has not adhered to prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have); consider possibility of pregnancy at time of first missed period and take appropriate diagnostic measures; if patient has adhered to prescribed regimen and misses two consecutive periods, rule out pregnancy Breast cancer Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk; studies do not show an association between ever (current or past) use of COCs and risk of breast cancer Some studies report a small increase in risk of breast cancer among current or recent users(<6 months since last use) and current users with longer duration of COC use A woman's risk depends on conditions where naturally high hormone levels persist for long periods of time including early-onset menstruation before age 12, late-onset menopause, after age 55, first child after age 30, nulliparity Pregnancy There is no use for contraception in pregnancy; therefore, this drug should be discontinued during pregnancy; epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs before conception or during early pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy; studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy Administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy; oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use; if the patient has not adhered to prescribed schedule, possibility of pregnancy should be considered at time of first missed period; oral contraceptive use should be discontinued if pregnancy is confirmed Lactation Contraceptive hormones and/or metabolites are present in human milk; COCs can reduce milk production in breastfeeding females; this reduction can occur at any time but is less likely to occur once breastfeeding is well-established; when possible, advise nursing female to use other methods of contraception until she discontinues breastfeeding The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from the drug or underlying maternal condition If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her childPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Levonorgestrel: Progestin; inhibits secretion of gonadotropins from pituitary; prevents follicular maturation and ovulation; stimulates growth of mammary tissues Ethinyl estradiol: Reduces release of luteinizing hormone-releasing hormone (LHRH) from hypothalamus; reduces release of gonadotropin from pituitary; increases synthesis of DNA, RNA, and various proteins in target tissues Absorption Bioavailability (levonorgestrel): Nearly 100%; rapidly and almost completely absorbed; not subject to first-pass metabolism; (ethinyl estradiol): 43%; rapidly and almost completely absorbed from gastrointestinal (GI) tract; subject to first-pass metabolism in gut mucosa and liver Distribution Protein bound (levonorgestrel): 97.5-99% (principally to sex hormone-binding globulin [SHBG] and, to a lesser extent, to serum albumin); (ethinyl estradiol): 95-97% (to serum albumin) Vd (levonorgestrel): 1.8 L/kg; (ethinyl estradiol): 4.3 L/kg Metabolism Levonorgestrel: Forms conjugated metabolites Ethinyl estradiol: Metabolized in liver by CYP3A4 to estriol and estrone Elimination Half-life (levonorgestrel): 22-49 hr (after single dose); (ethinyl estradiol): 12-23 hr Excretion (levonorgestrel and metabolites): Urine (40-68%) and feces (16-48%), mostly as glucuronide conjugates; (ethinyl estradiol): Urine and feces, as glucuronide and sulfate conjugates No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. 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