LEVORA 0.15/30-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVORA 0.15/30-28 (LEVORA 0.15/30-28).
Combination oral contraceptive containing ethinyl estradiol and levonorgestrel. Suppresses gonadotropin (FSH and LH) release from the pituitary, inhibiting ovulation. Also induces changes in cervical mucus (increasing viscosity) and endometrium (reducing receptivity) to impair sperm penetration and implantation.
| Metabolism | Levonorgestrel: Hepatic metabolism via reduction to tetrahydro derivatives, then conjugation with sulfate and glucuronide. CYP3A4 involved. Ethinyl estradiol: Hepatic metabolism via hydroxylation by CYP3A4, followed by methylation and conjugation (glucuronide/sulfate). Undergoes enterohepatic recirculation. |
| Excretion | Renal: ~50% (as glucuronide and sulfate conjugates of ethinyl estradiol and levonorgestrel); Fecal: ~50% (enterohepatic recirculation). |
| Half-life | Ethinyl estradiol: 13-27 hours (terminal); Levonorgestrel: 11-45 hours (terminal, dose-dependent due to SHBG binding). |
| Protein binding | Ethinyl estradiol: 97-98% bound to albumin; Levonorgestrel: 97-99% bound to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Ethinyl estradiol: 2.5-4.0 L/kg; Levonorgestrel: 1.8-2.6 L/kg (distribution to breast tissue, reproductive organs, and fat). |
| Bioavailability | Ethinyl estradiol: ~40-50% (first-pass metabolism); Levonorgestrel: ~95-100% (minimal first-pass effect). |
| Onset of Action | Oral: Contraceptive effect begins after 7 days of consistent dosing (suppression of ovulation). |
| Duration of Action | Contraceptive protection: 28-day cycle (21 active pills + 7 placebo); withdrawal bleed within 2-3 days after last active pill. |
| Molecular Weight | Ethinyl estradiol: 296.40 Da; Levonorgestrel: 312.45 Da |
| Action Class | Oral Contraceptive; Estrogen-Progestin Combination |
One tablet orally once daily at the same time each day for 28 days (21 active tablets containing 0.15 mg levonorgestrel and 0.03 mg ethinyl estradiol, followed by 7 placebo tablets).
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Not recommended in severe renal impairment or end-stage renal disease due to potential for fluid retention and hyperkalemia. |
| Liver impairment | Contraindicated in decompensated cirrhosis (Child-Pugh class B or C). Use with caution in mild hepatic impairment (Child-Pugh class A) with careful monitoring; consider alternative contraception. |
| Pediatric use | Postmenarchal adolescents: One tablet orally once daily per adult dosing schedule. Safety and efficacy established in females of reproductive age. |
| Geriatric use | Not indicated for postmenopausal women. No specific dosing adjustments; efficacy and safety not established in women over 40 years of age due to declining fertility and increased thrombotic risk. |
| 1st trimester | Ethinyl estradiol and levonorgestrel combination is contraindicated in pregnancy due to risk of fetal harm; use during first trimester is associated with possible teratogenic effects (cardiovascular defects, limb reduction) from estrogen component, though data are limited and not conclusive. The drug should be discontinued if pregnancy occurs. |
| 2nd trimester | Use during second trimester is contraindicated; available data do not indicate increased risk of major malformations with inadvertent exposure, but continued use is not recommended due to potential adverse effects on fetal development. |
| 3rd trimester | Use during third trimester is contraindicated due to association with fetal adrenal suppression (from progestin) and potential estrogenic effects; may increase risk of neonatal complications such as jaundice, respiratory distress, and hypoglycemia. |
Clinical note
Comprehensive clinical and safety monograph for LEVORA 0.15/30-28 (LEVORA 0.15/30-28).
| Placental transfer | Both ethinyl estradiol and levonorgestrel cross the placenta. Levonorgestrel is extensively transferred with fetal-maternal ratio approximately 1.0; ethinyl estradiol has lower but significant transfer. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events (e.g., myocardial infarction, thromboembolism, stroke) from combined oral contraceptive use, especially in women over 35 years of age and heavy smokers (>15 cigarettes/day). Women who use combined oral contraceptives should be strongly advised not to smoke.
| 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, Cerebrovascular accident |
PregnancyCurrent or past thrombophlebitis or venous thromboembolic disordersCerebrovascular or coronary artery diseaseKnown or suspected breast carcinomaEstrogen-dependent neoplasiaUndiagnosed abnormal genital bleedingKnown or suspected pregnancyHepatic adenoma or carcinomaActive liver disease or jaundice (including recurrent cholestatic jaundice)Hypersensitivity to any componentSmoking in women over 35 years old (increased cardiovascular risk)
| Precautions |
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| Breastfeeding | Small amounts of ethinyl estradiol and levonorgestrel are excreted in breast milk. Estrogen may reduce milk production and quality, especially in early postpartum. Use during breastfeeding is generally not recommended; alternative contraception should be considered. The American Academy of Pediatrics considers combination hormonal contraceptives as usually compatible with breastfeeding but may affect milk supply. |
| Lactation Rating | L3 (Moderately safe) - use only if benefit outweighs risk; monitor infant for jaundice, growth, and development. |
| Teratogenic Risk | FDA Pregnancy Category X. Contraindicated in pregnancy due to risk of fetal harm (limb defects, cardiac anomalies, feminization of male fetuses). Administration during first trimester associated with major birth defects. Second and third trimester exposure may cause fetal adrenal suppression and withdrawal bleeding. Use is not indicated during any trimester. |
| Fetal Monitoring | Pregnancy test prior to initiation. Monitor for signs of thromboembolism, hypertension, and hepatic dysfunction. In case of inadvertent use during pregnancy, discontinue immediately and counsel on potential risks. No specific fetal monitoring required if exposure occurs; offer prenatal diagnosis (ultrasound) for possible anomalies. |
| Fertility Effects | Reversible suppression of ovulation. Return to fertility is delayed; normal ovulation typically resumes within 1-3 months after discontinuation. No permanent adverse effects on fertility. Use does not increase risk of infertility. |
| Increased risk of venous thromboembolism (VTE) and arterial thrombosis (e.g., stroke, MI), especially in smokers, obese patients, and those with hypertension. Discontinue if thrombotic event occurs. Risk of hepatic neoplasia (benign/malignant). Elevated blood pressure; monitor regularly. Gallbladder disease. Carbohydrate/lipid metabolism effects; monitor diabetic patients. Headache (including migraine); discontinue if new or worsening. Uterine bleeding irregularities. Retinal vascular thrombosis; discontinue if vision changes. Rule out pregnancy before initiation. Not recommended for use during pregnancy. |
| Food/Dietary | No significant food interactions. Grapefruit juice may slightly increase estrogen levels; avoid excessive intake (more than 1 quart daily). St. John's wort may reduce contraceptive efficacy. |
| Clinical Pearls | Contains ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg. 28-day regimen: 21 active tablets followed by 7 placebo. Efficacy depends on adherence. Consider alternative contraception if patient is on enzyme-inducing anticonvulsants (e.g., carbamazepine, phenytoin) or certain antibiotics (rifampin). Missed pill protocol: if one active pill missed, take as soon as remembered and continue schedule; if two missed, take two pills for two days and use backup contraception for 7 days. Contraindicated in patients with history of DVT, PE, stroke, MI, migraine with aura (especially if age >35), breast cancer, hepatic tumors, uncontrolled hypertension, or pregnancy. |
| Patient Advice | Take one pill daily at the same time each day, preferably after a meal to reduce nausea. · Each pack contains 21 hormone pills (light pink) followed by 7 placebo pills (white); continue daily even during placebo week. · If you miss a dose, refer to the missed pill instructions in the package insert or consult your healthcare provider. · Smoking increases the risk of serious cardiovascular side effects; avoid smoking, especially if over age 35. · Use backup contraception (e.g., condoms) if you miss pills or start vomiting/diarrhea within 4 hours of taking a pill. · Report any signs of blood clots: leg pain/swelling, sudden chest pain, shortness of breath, severe headache, vision changes. · This medication does not protect against HIV or other sexually transmitted infections. · Store at room temperature (20-25°C) away from moisture and heat. · If you are scheduled for surgery, inform your surgeon you are taking this medication as it may need to be stopped temporarily. · Consult your doctor before starting any new medications, including over-the-counter drugs and herbal supplements. |