LEVORA 0.15/30-21
Clinical safety rating
cautionComprehensive clinical and safety monograph for LEVORA 0.15/30-21 (LEVORA 0.15/30-21).
Combination oral contraceptive: ethinyl estradiol suppresses gonadotropin release via negative feedback on hypothalamic-pituitary axis; levonorgestrel inhibits ovulation and thickens cervical mucus, impairing sperm penetration. Also induces endometrial atrophy.
| Metabolism | Levonorgestrel: hepatically metabolized via CYP3A4, CYP2C19, and CYP2C9; undergoes conjugation. Ethinyl estradiol: metabolized via CYP3A4 and sulfation (SULT1E1). |
| Excretion | Urine (50-60% as metabolites), feces (30-40% as glucuronides); <10% unchanged |
| Half-life | 20-30 hours for ethinyl estradiol; 2-4 hours for levonorgestrel. Steady-state reached in 5-7 days |
| Protein binding | Levonorgestrel: 97-98% (SHBG, albumin); Ethinyl estradiol: 97-98% (albumin, SHBG) |
| Volume of Distribution | Levonorgestrel: 1.4 L/kg; Ethinyl estradiol: 2.4 L/kg; extensive tissue distribution |
| Bioavailability | Oral: levonorgestrel ~100%; ethinyl estradiol 38-48% (first-pass metabolism) |
| Onset of Action | Oral: 24-48 hours for contraceptive effect; 7-day continuous dosing required for full ovarian suppression |
| Duration of Action | 24 hours per active tablet; withdrawal bleed occurs 2-3 days after last active tablet; contraceptive protection persists for 7 days of placebo |
| Molecular Weight | 376.9 |
| Action Class | Combination Oral Contraceptive (Estrogen-Progestin) |
One tablet orally once daily for 21 days, followed by 7 tablet-free days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment; use caution. |
| Liver impairment | Contraindicated in acute liver disease or severe (Child-Pugh C) hepatic impairment. For Child-Pugh A or B, use is not recommended; alternative contraception advised. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults: one tablet orally once daily for 21 days, then 7 days off. |
| Geriatric use | Not indicated for use after menopause. No specific geriatric dosing considerations due to lack of indication. |
| 1st trimester | Contraindicated due to risk of birth defects; not indicated for pregnancy prevention. Pregnancy Category X. |
| 2nd trimester | Contraindicated; not used in pregnancy. Avoid exposure. |
| 3rd trimester | Contraindicated; no obstetric indication. |
Clinical note
Comprehensive clinical and safety monograph for LEVORA 0.15/30-21 (LEVORA 0.15/30-21).
| Placental transfer | Minimal placental transfer; synthetic estrogen and progestin cross placenta but not used during pregnancy. |
| Breastfeeding | Excretion into breast milk minimal; no adverse effects reported in infants. Caution in early postpartum due to theoretical risk of reduced milk production. Generally compatible with breastfeeding. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | First trimester: No increased risk of birth defects based on large epidemiological studies. Second and third trimesters: Avoid use due to potential adverse effects on fetal development, including feminization of male fetuses and hepatic adenoma. Overall, pregnancy is a contraindication for levonorgestrel/ethinyl estradiol. |
| Fetal Monitoring | Monitor blood pressure, liver function, and glucose levels. Assess for thrombotic events. During pregnancy, fetal ultrasound for development if inadvertent exposure occurs. |
| Fertility Effects | Estrogen-progestin combinations reversibly suppress ovulation. After discontinuation, return to fertility may be delayed by 1-2 cycles but no permanent effect. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Risk increases with age and smoking intensity (especially >35 years). Women >35 years who smoke should not use combination oral contraceptives.
| Common Effects | Nausea, Headache, Breast tenderness, Weight changes, Irregular menstrual bleeding, Mood changes |
| Serious Effects | Venous thromboembolism (deep vein thrombosis, pulmonary embolism), Arterial thromboembolism (myocardial infarction, stroke), Hepatic adenoma or hepatocellular carcinoma, Hypertension, Gallbladder disease, Cerebral hemorrhage |
PregnancyThrombophlebitisThromboembolic disordersCerebral vascular diseaseCoronary artery diseaseKnown or suspected breast cancerUndiagnosed abnormal genital bleedingKnown or suspected estrogen-dependent neoplasiaBenign or malignant liver tumorActive liver diseaseHypersensitivity to any component
| Precautions | Thrombotic disorders (DVT, PE, stroke, MI), Cerebral hemorrhage, Hepatic neoplasia (benign/malignant), Gallbladder disease, Hypertension, Carbohydrate/lipid metabolism effects, Ocular lesions (e.g., retinal thrombosis), Headache/migraine, Uterine bleeding irregularities, Depression, Contact lens intolerance |
| Food/Dietary | No specific food restrictions. Grapefruit juice may increase estrogen levels; avoid large quantities. Maintain consistent dietary habits to avoid interference with absorption. |
| Clinical Pearls | Levonorgestrel/ethinyl estradiol is a combination oral contraceptive. Advise patients to take at the same time daily. Breakthrough bleeding is more common in first few cycles. Missed pill management: if less than 12 hours, take immediately; if more than 12 hours, check package insert. Consider drug interactions with rifampin, certain anticonvulsants, and antibiotics. Not recommended in smokers over 35 and those with history of migraines with aura, hypertension, or thromboembolism. |
| Patient Advice | Take one pill at the same time every day. · If you miss a pill, refer to the patient leaflet for instructions. · Use backup contraception (e.g., condoms) if you miss pills or have vomiting/diarrhea. · Common side effects include nausea, spotting, and breast tenderness; these often improve after 3 months. · Do not smoke while taking this medication, especially if over age 35. · This medication does not protect against HIV or other sexually transmitted infections. |
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