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  • Beyaz
    (Levomefolate Calcium, Ethinyl Estradiol, Drospirenone) - Bayer Healthcare

    BOXED WARNING

    Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. Risk increases with age (>35 yrs) and with the number of cigarettes smoked. Should not be used by women who are >35 yrs of age and smoke.

    THERAPEUTIC CLASS

    Estrogen/progestogen combination

    DEA CLASS

    RX

    INDICATIONS

    Prevention of pregnancy. Treatment of symptoms of premenstrual dysphoric disorder (PMDD). Treatment of moderate acne vulgaris in women ≥14 yrs of age who have achieved menarche and who desire an oral contraceptive for birth control. To raise folate levels for the purpose of reducing the risk of neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuation.

    ADULT DOSAGE

    Adults: Contraception/Acne/PMDD: 1 tab qd for 28 days, then repeat. Start 1st Sunday after menses begin or 1st day of menses. Take at the same time each day, preferably pm pc or hs.

    PEDIATRIC DOSAGE

    Pediatrics: Postpubertal: Contraception/Acne (≥14 Yrs)/PMDD: 1 tab qd for 28 days, then repeat. Start 1st Sunday after menses begin or 1st day of menses. Take at the same time each day, preferably pm pc or hs.

    HOW SUPPLIED

    Tab: (Drospirenone [DRSP]-Ethinyl Estradiol [EE]-Levomefolate calcium) 3mg-0.02mg-0.451mg; Tab: (Levomefolate calcium) 0.451mg

    CONTRAINDICATIONS

    Renal impairment, adrenal insufficiency, high risk of arterial/venous thrombotic disease (eg, smoking if >35 yrs of age, history/presence of deep vein thrombosis/pulmonary embolism, cerebrovascular disease, coronary artery disease, thrombogenic valvular or thrombogenic rhythm diseases of the heart [eg, subacute bacterial endocarditis with valvular disease, atrial fibrillation], inherited/acquired hypercoagulopathies, uncontrolled HTN, diabetes mellitus [DM] with vascular disease, headaches with focal neurological symptoms or migraine with/without aura if >35 yrs of age), undiagnosed abnormal uterine bleeding, history/presence of breast or other estrogen-/progestin-sensitive cancer, benign/malignant liver tumors, liver disease, pregnancy.

    WARNINGS/PRECAUTIONS

    Increased risk of venous thromboembolism and arterial thromboses (eg, stroke, myocardial infarction). D/C if arterial/deep venous thrombotic events, unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions occur; evaluate for retinal vein thrombosis immediately. Caution in women with cardiovascular disease (CVD) risk factors. D/C at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism. Avoid use in patients predisposed to hyperkalemia. May increase risk of breast cancer, cervical cancer, intraepithelial neoplasia, and gallbladder disease. Hepatic adenoma and increased risk of hepatocellular carcinoma reported; d/c if jaundice or acute/chronic disturbances of liver function occur. Cholestasis may occur with history of pregnancy-related cholestasis. Increased BP reported; d/c if BP rises significantly. May decrease glucose tolerance; monitor prediabetic and diabetic patients. Consider alternative contraception with uncontrolled dyslipidemia. Increased risk of pancreatitis with hypertriglyceridemia or family history thereof. May increase frequency/severity of migraine; d/c if new headaches that are recurrent, persistent, or severe develop. Unscheduled bleeding and spotting may occur; rule out pregnancies or malignancies. Caution with history of depression; d/c if depression recurs to serious degree. May change results of lab tests. Folate may mask vitamin B12 deficiency. May induce/exacerbate angioedema in patients with hereditary angioedema. Chloasma may occur, especially with history of chloasma gravidarum; avoid sun exposure or UV radiation. Women who do not breastfeed may start therapy no earlier than 4 weeks postpartum.

    ADVERSE REACTIONS

    Menstrual irregularities, N/V, headache/migraine, breast pain/tenderness, fatigue.

    DRUG INTERACTIONS

    Risk of hyperkalemia with ACE inhibitors, angiotensin II receptor antagonists, K+-sparing diuretics, K+ supplementation, heparin, aldosterone antagonists, and NSAIDs. Reduced effectiveness or increased breakthrough bleeding with enzyme inducers, including CYP3A4, (eg, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, St. John's wort). Significant changes (increase/decrease) in plasma estrogen and progestin levels with HIV/hepatitis C virus protease inhibitors or non-nucleoside reverse transcriptase inhibitors. Pregnancy reported with use of hormonal contraceptives and antibiotics. Increased levels with atorvastatin, ascorbic acid, acetaminophen, and CYP3A4 inhibitors (eg, itraconazole, ketoconazole). May decrease plasma concentrations of lamotrigine and reduce seizure control; adjust dose of lamotrigine. Increases thyroid-binding globulin; may need to increase dose of thyroid hormone in patients on thyroid hormone replacement therapy. May decrease pharmacological effect of antifolate drugs (eg, antiepileptics [phenytoin], methotrexate, pyrimethamine). Reduced folate levels via inhibition of dihydrofolate reductase enzyme (eg, methotrexate, sulfasalazine), reduced folate absorption (eg, cholestyramine), or unknown mechanism (eg, antiepileptics [carbamazepine, phenytoin, phenobarbital, primidone, valproic acid]).

    PREGNANCY

    Contraindicated in pregnancy, not for use in nursing.

    MECHANISM OF ACTION

    Estrogen/progestogen oral contraceptive; acts by primarily suppressing ovulation. Also causes cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation. (Levomefolate calcium) Folate supplementation.

    PHARMACOKINETICS

    Absorption: DRSP: Absolute bioavailability (76%); (Cycle 1/Day 21) Cmax=70.3ng/mL; Tmax=1.5 hrs; AUC=763ng•h/mL. EE: Absolute bioavailability (40%); (Cycle 1/Day 21) Cmax=45.1pg/mL; Tmax=1.5 hrs; AUC=220pg•h/mL. Levomefolate: Tmax=0.5-1.5 hrs. Distribution: Found in breast milk; DRSP: Vd=4L/kg; serum protein binding (97%). EE: Vd=4-5L/kg; serum albumin binding (98.5%). Metabolism: DRSP: Liver, via CYP3A4 (minor). EE: Hydroxylation (via CYP3A4), conjugation with glucuronide and sulfate. Elimination: DRSP: Urine, feces; T1/2=30 hrs. EE: Urine, feces; T1/2=24 hrs. Levomefolate (L-5-methyl-THF): Urine, feces; T1/2=4-5 hrs.

    ASSESSMENT

    Assess for renal impairment, abnormal uterine bleeding, adrenal insufficiency, known or suspected pregnancy, and other conditions where treatment is cautioned or contraindicated. Assess use in women who are >35 yrs of age and smoke, have CVD and arterial/venous thrombosis risk factors, predisposition to hyperkalemia, pregnancy-related cholestasis, HTN, DM, uncontrolled dyslipidemia, history of hypertriglyceridemia, history of depression, hereditary angioedema, and history of chloasma. Assess for possible drug interactions.

    MONITORING

    Monitor for bleeding irregularities, venous/arterial thrombotic and thromboembolic events, cervical cancer or intraepithelial neoplasia, retinal vein thrombosis or any other ophthalmic changes, jaundice, acute/chronic disturbances in liver function, new/worsening headaches or migraines, serious depression, cholestasis with history of pregnancy-related cholestasis, and pancreatitis. Monitor K+ levels, thyroid function if receiving thyroid replacement therapy, glucose levels in DM or prediabetes, lipids with dyslipidemia, and check BP annually.

    PATIENT COUNSELING

    Counsel that cigarette smoking increases the risk of serious CV events from COC use and to avoid use in women who are >35 yrs old and smoke. Inform that drug does not protect against HIV infection and other sexually transmitted diseases. Instruct to take at the same time every day, preferably pm pc or hs. Instruct on what to do if pills are missed or vomiting occurs within 3-4 hrs after taking tab. Inform that COCs may reduce breast milk production. Inform that amenorrhea may occur and pregnancy should be ruled out if amenorrhea occurs in ≥2 consecutive cycles. Counsel to report if taking folate supplements and advise to maintain folate supplementation upon discontinuation due to pregnancy. Advise to inform physician of preexisting medical conditions and/or drugs currently being taken. Counsel to use additional method of contraception when enzyme inducers are used with COCs. Counsel women who start COCs postpartum and have not yet had a period to use additional method of contraception until drug taken for 7 consecutive days. Instruct to d/c if pregnancy occurs during treatment.

    ADMINISTRATION/STORAGE

    Administration: Oral route. Storage: 25°C (77°F); excursions permitted to 15-30°C (59-86°F).