LO/OVRAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LO/OVRAL (LO/OVRAL).
Combination estrogen-progestin oral contraceptive; suppresses gonadotropin release, primarily FSH and LH, inhibiting ovulation; increases viscosity of cervical mucus, impeding sperm penetration; alters endometrial receptivity.
| Metabolism | Ethinyl estradiol is primarily metabolized by CYP3A4; norgestrel is metabolized via reduction and conjugation; both undergo first-pass metabolism. |
| Excretion | Urine (50-60% as conjugated metabolites), feces (30-40% as metabolites), enterohepatic recirculation present. |
| Half-life | Norgestrel (levonorgestrel): 11-45 hours (mean ~24 hours); ethinyl estradiol: 7-21 hours (mean ~14 hours). Half-life increases slightly with repeated dosing due to saturable metabolism. |
| Protein binding | Levonorgestrel: 97-99% (primarily to sex hormone-binding globulin, SHBG, and albumin); ethinyl estradiol: 97-98% (primarily to albumin, increases SHBG levels). |
| Volume of Distribution | Levonorgestrel: 1.0-1.3 L/kg; ethinyl estradiol: 2.3-3.0 L/kg. Reflects extensive tissue distribution and binding. |
| Bioavailability | Oral: levonorgestrel ~100% (first-pass metabolism <10%), ethinyl estradiol 38-48% due to first-pass conjugation in gut wall and liver. |
| Onset of Action | Oral: 24 hours for ovulation suppression; full contraceptive effect after 7 days of continuous dosing. |
| Duration of Action | Oral: 24 hours per dose; requires daily administration for consistent contraceptive effect. |
One tablet (30 mcg ethinyl estradiol, 0.3 mg norgestrel) orally once daily for 28-day cycle (21 active, 7 placebo).
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate impairment. Not recommended in severe renal impairment (eGFR <30 mL/min/1.73m²) due to limited data. |
| Liver impairment | Contraindicated in Child-Pugh class B or C (active liver disease, jaundice, or impaired synthetic function). Use discontinued if hepatic function deteriorates. |
| Pediatric use | Post-menarche adolescents: Same dosing as adults (30 mcg ethinyl estradiol/0.3 mg norgestrel daily). Not indicated pre-menarche. |
| Geriatric use | Not indicated for postmenopausal women. Higher risk of thromboembolism and cardiovascular events in women >40 years, especially if smoking or other risk factors. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LO/OVRAL (LO/OVRAL).
| Breastfeeding | Contraindicated during breastfeeding due to potential adverse effects on milk production and infant hormonal balance. M/P ratio not established; ethinyl estradiol and norgestrel are excreted into human milk in small amounts but insufficient data on infant exposure. |
| Teratogenic Risk | First trimester: No increased risk of major malformations based on epidemiological studies. Second/third trimesters: Exposure may increase risk of fetal liver tumors (rare) and possibly cardiovascular malformations; contraindicated due to feminization of male fetus. Post-market reports: Possible association with neonatal jaundice, cholestasis, and transient hormonal effects. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from oral contraceptive use; risk increases with age (especially in women over 35 years) and with heavy smoking (≥15 cigarettes/day); women should be strongly advised not to smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders; cerebrovascular or coronary artery disease; known or suspected breast carcinoma; estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; known or suspected pregnancy; hepatic adenoma or malignancy; cholestatic jaundice of pregnancy or jaundice with prior pill use; active liver disease; hypersensitivity to any component; cigarette smoking in women ≥35 years; uncontrolled hypertension; diabetes with vascular involvement; headaches with focal neurological symptoms; major surgery with prolonged immobilization.
| Precautions | Increased risk of thromboembolic disorders (e.g., MI, stroke, VTE); hepatic adenoma; risk of breast cancer; hypertension; gallbladder disease; impaired glucose tolerance; cholestatic jaundice; ocular lesions (e.g., retinal thrombosis); use in pregnancy; fluid retention; hereditary angioedema. |
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| Fetal Monitoring | Monitor for signs of thromboembolism, hypertension, cholestasis, and glucose intolerance. Fetal monitoring: Serial ultrasound if exposure in second/third trimester to rule out congenital anomalies; assess liver function and bilirubin in neonate. |
| Fertility Effects | No permanent impairment of fertility after discontinuation; normal ovulation typically resumes within 1-3 months. Chronic use may delay return to fertility. |