OVRAL
Clinical safety rating
cautionComprehensive clinical and safety monograph for OVRAL (OVRAL).
OVRAL is a combination oral contraceptive containing ethinyl estradiol and norgestrel. It inhibits ovulation by suppressing gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus, reducing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release from the pituitary. Additionally, it increases cervical mucus viscosity and alters endometrial receptivity, impeding sperm penetration and implantation.
| Metabolism | Ethinyl estradiol is primarily metabolized by CYP3A4, with sulfation and glucuronidation pathways. Norgestrel is hydroxylated via CYP3A4 and undergoes reduction and conjugation. |
| Excretion | Renal (60% as metabolites, ~40% unchanged); biliary/fecal (40%) |
| Half-life | Norgestrel: 24–32 hours; Ethinyl estradiol: 12–18 hours; steady-state achieved after 5–7 days |
| Protein binding | Norgestrel: 93–97% bound to SHBG; Ethinyl estradiol: 97–98% bound to albumin and SHBG |
| Volume of Distribution | Norgestrel: 1.5–2.5 L/kg; Ethinyl estradiol: 2.5–4.0 L/kg; extensive tissue distribution |
| Bioavailability | Norgestrel: ~90%; Ethinyl estradiol: ~45–50% due to first-pass metabolism |
| Onset of Action | Oral: 24–36 hours for contraceptive effect; requires 7 days of continuous dosing for full efficacy |
| Duration of Action | 24 hours; requires daily dosing to maintain contraceptive effect; withdrawal bleeding occurs during placebo week |
| Molecular Weight | 312.45 |
| Brand Substitutes | Levopauz 0.05mg/0.25mg Tablet, Esro G Tablet, X-Out 21 Tablet, Dear Tablet, Florina G 0.05mg/0.25mg Tablet |
One tablet (norgestrel 0.3 mg with ethinyl estradiol 0.03 mg) orally once daily for 21 days followed by 7 days of placebo.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment is required for mild to moderate renal impairment. Use with caution in severe renal impairment or end-stage renal disease due to potential for hormonal accumulation and adverse effects. |
| Liver impairment | Contraindicated in patients with acute or chronic hepatic disease or history of hepatic tumors (benign or malignant). In Child-Pugh class A (mild impairment), use with caution; in Child-Pugh class B or C (moderate to severe impairment), contraindicated. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults: one tablet orally daily for 21 days followed by 7 days of placebo. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific geriatric dosing adjustments; consider increased risk of thrombosis and cardiovascular events in older women of reproductive age. |
| 1st trimester | Contraindicated due to risk of congenital anomalies (e.g., cardiovascular, limb defects) from estrogen/progestin exposure during organogenesis. |
| 2nd trimester | Not recommended; may cause adverse effects such as fetal adrenal suppression or masculinization of female fetus. |
| 3rd trimester | Avoid use; potential for feminization of male fetus or adrenal suppression in newborn. |
Clinical note
Comprehensive clinical and safety monograph for OVRAL (OVRAL).
| Placental transfer | Estradiol and norgestrel cross the placenta; detected in fetal tissues and cord blood. High transfer for estradiol (partial) and norgestrel (moderate). |
| Breastfeeding | Estrogen and progestin pass into breast milk in small amounts; may reduce milk production and quality, especially with high doses. Use only if clearly needed and monitor infant for jaundice or breast enlargement. |
| Lactation Rating | L3 (Moderately Safe) - Limited data; likely compatible with caution, but avoid high doses. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: Known teratogen; associated with cardiovascular defects, neural tube defects, and limb reduction defects. Second trimester: Risk of fetal masculinization with progestins. Third trimester: Potential for feminization of male fetuses and virilization of female fetuses; increased risk of fetal adrenal suppression. |
| Fetal Monitoring | Pregnancy testing before initiation. Ultrasound for fetal anomalies if exposed. Monitor maternal blood pressure, liver function, and signs of thromboembolism during pregnancy. Fetal monitoring for growth and development anomalies after exposure. |
| Fertility Effects | Suppresses ovulation during use resulting in contraceptive effect. After discontinuation, return to fertility may be delayed but is typically within 1-3 months. Long-term use does not impair future fertility; no increased risk of congenital anomalies in subsequent pregnancies. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age and with the number of cigarettes smoked, and is particularly marked in women over 35 years of age. Women who use combination oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
Known or suspected pregnancyHistory of thrombophlebitis or thromboembolic disordersCerebral vascular or coronary artery diseaseKnown or suspected carcinoma of the breast or endometriumUndiagnosed abnormal genital bleedingCholestatic jaundice of pregnancy or jaundice with prior pill useHepatic adenoma or carcinomaKnown hypersensitivity to any component
| Precautions | Thrombotic disorders: venous thromboembolism, arterial thromboembolism, stroke, myocardial infarction, Hepatic neoplasia: liver tumors (benign and malignant), Cervical cancer: increased risk with long-term use, Hypertension, Gallbladder disease, Carbohydrate and lipid metabolic effects, Headache (including migraine), Bleeding irregularities (breakthrough bleeding, spotting, amenorrhea), Depression, Ocular lesions (e.g., retinal thrombosis), Contact lens intolerance |
| Food/Dietary | Avoid grapefruit juice as it may increase estrogen levels and side effect risk. St. John's wort (herbal supplement) reduces contraceptive efficacy by inducing CYP3A4. No specific food restrictions; maintain consistent intake to minimize GI upset. |
| Clinical Pearls | Ovral (norgestrel/ethinyl estradiol) is a combined oral contraceptive with high progestin potency, increasing the risk of venous thromboembolism. Consider for patients needing reliable contraception but avoid in those with migraine with aura, history of thromboembolic disorders, or liver disease. Breakthrough bleeding is common; manage by adjusting pill schedule or switching to a higher estrogen dose. Drug interactions with cytochrome P-450 inducers (e.g., rifampin, anticonvulsants) may reduce efficacy; consider backup contraception. |
| Patient Advice | Take one tablet at the same time daily; missed pills require backup contraception. · Common side effects include nausea, headache, and breast tenderness; these often improve after a few cycles. · Report symptoms of thromboembolism (leg pain/swelling, sudden chest pain or dyspnea) or stroke (severe headache, vision changes). · Do not smoke while on Ovral; smoking increases risk of serious cardiovascular side effects, especially if over 35 years old. · Antibiotics (except rifampin) do not reduce efficacy; but certain anticonvulsants and St. John's wort do; use backup method with these. |
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