LO/OVRAL
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 312.4 |
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 | Contraindicated due to risk of congenital anomalies including cardiovascular and limb defects; should not be used during first trimester. |
| 2nd trimester | Contraindicated; exposure may increase risk of adverse fetal outcomes; not indicated for use during pregnancy. |
| 3rd trimester | Contraindicated; may cause fetal harm; avoid use in third trimester. |
Clinical note
Comprehensive clinical and safety monograph for LO/OVRAL (LO/OVRAL).
| Placental transfer | Crosses placenta; sufficient transfer to fetus detectable in fetal tissues. |
| Breastfeeding | Excreted in breast milk; may reduce milk production and affect infant; consider alternative contraception during breastfeeding. |
| Lactation Rating | L4 |
| 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. |
| 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. |
■ 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 |
Known or suspected pregnancyThrombophlebitis or thromboembolic disordersCerebral vascular diseaseCoronary artery diseaseKnown or suspected carcinoma of the breastUndiagnosed abnormal genital bleedingCholestatic jaundice of pregnancy or jaundice with prior pill useHepatic adenoma or carcinomaKnown hypersensitivity to any component
| 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. |
| Food/Dietary | No significant food interactions. Grapefruit juice may increase ethinyl estradiol levels via CYP3A4 inhibition, but clinical relevance is minimal with low-dose pills. Avoid using St. John's wort, which may decrease contraceptive efficacy. |
| Clinical Pearls | Lo/Ovral is a low-dose combined oral contraceptive containing ethinyl estradiol and norgestrel. Not recommended for use in women with BMI > 35 kg/m² due to increased thromboembolic risk. Advise consistent daily timing within a 3-hour window to maintain efficacy. Missed pill management: if one pill is missed >12 hours late, take missed pill and continue with next pill at normal time; if two or more pills are missed, take the most recent missed pill and use backup contraception for 7 days. Consider CYP3A4 inducers (e.g., rifampin, St. John's wort) that may reduce efficacy. |
| Patient Advice | Take one tablet daily at the same time every day. · Do not skip pills; if you miss a pill, follow the missed pill instructions in the package insert. · Use backup contraception (e.g., condoms) if you vomit or have severe diarrhea within 4 hours of taking a pill. · Avoid smoking, especially if over 35 years old, as it increases risk of serious cardiovascular side effects. · Tell your healthcare provider about all medications and supplements you take, as some may interfere with birth control effectiveness. · Lo/Ovral does not protect against HIV or other sexually transmitted infections. · Store at room temperature away from moisture and heat. |
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