OVRAL-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OVRAL-28 (OVRAL-28).
Combination oral contraceptive: suppresses gonadotropin release via estrogen and progestin, inhibiting ovulation, thickening cervical mucus, and altering endometrial lining.
| Metabolism | Ethinyl estradiol: primarily hepatic via CYP3A4, undergoes first-pass metabolism; norgestrel: hepatic reduction and conjugation, partially via CYP3A4. |
| Excretion | Renal: ~40% as metabolites; fecal: ~60% via biliary excretion, primarily as glucuronide and sulfate conjugates. |
| Half-life | Ethinyl estradiol: terminal half-life 13-27 hours (mean ~17 hours); norgestrel: terminal half-life 11-45 hours (mean ~24 hours). Clinical context: steady-state reached within 5-7 days; accumulation minimal with daily dosing. |
| Protein binding | Ethinyl estradiol: 97-98% bound, primarily to albumin; norgestrel: 93-95% bound, primarily to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Ethinyl estradiol: 2.5-4.0 L/kg; norgestrel: 2.0-3.5 L/kg. High Vd indicates extensive tissue distribution and binding. |
| Bioavailability | Oral: ethinyl estradiol ~40-50% (due to first-pass metabolism); norgestrel ~60-70% (variable due to presystemic metabolism). |
| Onset of Action | Oral: contraceptive effect requires 7 days of consistent dosing; ovulation suppression achieved within 3-7 days; endometrial changes occur within 5-7 days. |
| Duration of Action | Contraceptive protection persists for 24 hours with daily dosing; after discontinuation, ovulation resumes typically within 2-4 weeks, but may be delayed in some individuals. |
One tablet (norgestrel 0.3 mg, ethinyl estradiol 0.03 mg) orally once daily for 21 consecutive days, followed by 7 days of placebo.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Insufficient data for severe renal impairment (CrCl <30 mL/min); use with caution due to potential fluid retention. |
| Liver impairment | Contraindicated in acute hepatitis, hepatic adenomas, or severe cirrhosis (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), consider alternative therapy; if used, monitor liver function closely and reduce dose if tolerated. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults (one tablet daily). |
| Geriatric use | Not indicated for use after menopause. No specific dosing adjustments provided for elderly patients; consider increased risk of thromboembolic events and cardiovascular disease. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OVRAL-28 (OVRAL-28).
| Breastfeeding | Contraindicated during breastfeeding. Estrogens and progestins are excreted in human milk in low concentrations (M/P ratio not established). Potential for adverse effects on the infant including jaundice and breast enlargement. |
| Teratogenic Risk | Pregnancy category X. First trimester: risk of congenital malformations (neural tube defects, cardiovascular anomalies) and spontaneous abortion. Second and third trimesters: associated with fetal adrenal suppression, hepatic impairment, and potential for masculinization of female genitalia. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Combination oral contraceptives are contraindicated in women over 35 who smoke.
| Common Effects | Nausea Headache Breast pain Irregular uterine bleeding |
| Serious Effects |
["Current or history of thrombotic disorders","Known or suspected breast carcinoma","Undiagnosed abnormal genital bleeding","Hepatic adenoma or carcinoma","Known or suspected pregnancy","Hypersensitivity to any component"]
| Precautions | ["Increased risk of thrombotic disorders (venous thromboembolism, stroke, MI)","Elevated blood pressure","Gallbladder disease","Hepatic neoplasia","Glucose intolerance","Retinal thrombosis","Depression"] |
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| Fetal Monitoring |
| Pregnancy test before initiation; monitor for thrombotic events, hypertension, hepatic function, and signs of fetal distress if accidental exposure occurs. |
| Fertility Effects | Reversible inhibition of ovulation during use. No long-term impact on fertility after discontinuation; return to normal ovulatory cycles typically occurs within 1-3 months. |