LEVORA 0.15/30-21
Clinical safety rating: caution
Comprehensive 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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVORA 0.15/30-21 (LEVORA 0.15/30-21).
| Breastfeeding | Levonorgestrel and ethinyl estradiol are excreted in breast milk. M/P ratio for levonorgestrel is approximately 1.0; for ethinyl estradiol, it is 0.4. Use may reduce milk production and composition. Not recommended during lactation. |
| 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. |
■ 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.
| Serious Effects |
["Hypersensitivity to any component","Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast carcinoma","Estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use","Hepatic adenoma or carcinoma","Pregnancy (known or suspected)","Heavy smoking (>15 cigarettes/day) in women ≥35 years"]
| 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"] |
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| 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. |