LO/OVRAL-28
Clinical safety rating
cautionComprehensive clinical and safety monograph for LO/OVRAL-28 (LO/OVRAL-28).
Combination of norgestrel, a progestin, and ethinyl estradiol, an estrogen; suppresses gonadotropin secretion (FSH and LH) primarily via progestational activity, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial development, reducing implantation likelihood.
| Metabolism | Hepatic via CYP3A4 for ethinyl estradiol; norgestrel metabolized via reduction and conjugation. |
| Excretion | Renal (approx. 50% as metabolites, <1% unchanged); biliary/fecal (approx. 50% as metabolites). |
| Half-life | Norgestrel: 20-40 hours; Ethinyl estradiol: 13-27 hours. Steady-state achieved after 3-5 half-lives. |
| Protein binding | Norgestrel: 93-99% (primarily SHBG and albumin); Ethinyl estradiol: 97-98% (primarily albumin and SHBG). |
| Volume of Distribution | Norgestrel: 3.0 L/kg; Ethinyl estradiol: 4.0 L/kg. |
| Bioavailability | Oral: Norgestrel 85-90%; Ethinyl estradiol 38-48% due to first-pass metabolism. |
| Onset of Action | Oral: 7 days of continuous dosing for full contraceptive effect. |
| Duration of Action | 24 hours (requires daily dosing for continuous contraception). |
| Molecular Weight | 312.4 |
One tablet orally once daily for 28 days. Each tablet contains 0.3 mg norgestrel and 0.03 mg ethinyl estradiol. Active tablets (21 days) followed by placebo tablets (7 days).
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. However, use with caution in patients with renal dysfunction due to potential fluid retention. |
| Liver impairment | Contraindicated in patients with Child-Pugh Class B or C cirrhosis. For Child-Pugh Class A, use with caution; limited data, but no specific dose adjustment recommended. |
| Pediatric use | Not indicated for use before menarche. For post-menarchal adolescents, the same dosing as adults: one tablet orally daily for 28-day cycles. |
| Geriatric use | Not indicated in postmenopausal women. No geriatric-specific dosing; not for use in elderly due to lack of need for contraception after menopause. |
| 1st trimester | Contraindicated in pregnancy. Do not use to test for pregnancy. No evidence of safe use. |
| 2nd trimester | Contraindicated. Use only if clearly needed? No—avoid. Not indicated. |
| 3rd trimester | Contraindicated. Avoid use; no benefit in pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for LO/OVRAL-28 (LO/OVRAL-28).
| Placental transfer | Yes, crosses placenta; known teratogen. |
| Breastfeeding | Excreted in small amounts; may reduce milk production and composition. Use only if no alternative. Not recommended for lactating women. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: No known association with major congenital anomalies, but small increased risk of cardiovascular defects and limb reduction defects reported in some studies. Second/third trimesters: Use not recommended due to potential adverse effects on fetal development including virilization of female fetus and hepatic adenoma; contraindicated in known pregnancy. |
| Fetal Monitoring | Monitor blood pressure, liver function, and signs of thrombotic events due to increased risk in pregnancy. Evaluate for fetal anomalies if inadvertently exposed; no specific fetal testing required unless other risk factors present. |
| Fertility Effects | Suppresses ovulation; return to fertility may be delayed by 1–2 months after discontinuation. Long-term use associated with no permanent impairment of fertility. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age and smoking intensity (especially in women over 35). Women should be strongly advised not to smoke.
| Serious Effects |
PregnancyThrombophlebitis or thromboembolic disordersKnown or suspected breast cancerUndiagnosed abnormal genital bleedingBenign or malignant liver tumorKnown or suspected estrogen-dependent neoplasia
| Precautions | Thrombotic disorders (e.g., venous thromboembolism, stroke, myocardial infarction); hepatic neoplasia; hypertension; gallbladder disease; carbohydrate/lipid effects; ocular lesions; breakthrough bleeding; missed periods; ectopic pregnancy risk; lactation; depression. |
| Food/Dietary | No significant food interactions. Grapefruit juice does not notably affect ethinyl estradiol levels, but consistent intake is recommended to maintain uniform hormone levels. Avoid excessive alcohol consumption as it may impair liver function and alter hormone metabolism. |
| Clinical Pearls | LO/OVRAL-28 is a combination oral contraceptive containing norgestrel and ethinyl estradiol. It is indicated for pregnancy prevention. The 28-day regimen includes 21 active pills and 7 placebo pills. Counsel patients to take at the same time daily. Breakthrough bleeding is common in the first few cycles. If a dose is missed, follow the specific package instructions. Anti-infectives like rifampin may reduce efficacy; additional contraception is recommended. |
| Patient Advice | Take one pill daily at the same time each day. · If you miss a pill, refer to the package insert for instructions; use backup contraception if needed. · Common side effects include nausea, breast tenderness, and spotting, which usually improve after a few cycles. · Smoking increases risk of serious cardiovascular side effects; do not smoke while taking this medication. · Inform your healthcare provider if you have a history of blood clots, migraines with aura, or liver disease. |
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