ENOVID-E
Clinical safety rating
cautionComprehensive clinical and safety monograph for ENOVID-E (ENOVID-E).
Combination estrogen-progestin contraceptive. Suppresses gonadotropin release, inhibits ovulation, increases cervical mucus viscosity, and alters endometrial morphology.
| Metabolism | Metabolized via hepatic cytochrome P450 enzymes (CYP3A4) and conjugated with glucuronic acid and sulfate. Enterohepatic recirculation occurs. |
| Excretion | Renal (50-60% as metabolites, <1% unchanged); fecal (40-50%) |
| Half-life | Norethynodrel: 5-10 hours; mestranol: 2-5 hours (metabolized to ethinyl estradiol, half-life 10-20 hours). Steady-state reached in 5-7 days. |
| Protein binding | Norethynodrel: 95-98% (albumin); mestranol: 97-99% (albumin and SHBG) |
| Volume of Distribution | Norethynodrel: 2-4 L/kg; mestranol: 3-5 L/kg; extensive tissue distribution |
| Bioavailability | Oral: >90% for norethynodrel; mestranol: 40-60% (first-pass metabolism) |
| Onset of Action | Oral: 24-48 hours for contraceptive effect (requires 7 days of dosing for full inhibition of ovulation) |
| Duration of Action | Contraceptive effect persists for 1 month per cycle; after discontinuation, fertility returns within 1-2 cycles |
| Molecular Weight | 310.4 |
5 mg orally once daily for 20 days starting on day 5 of menstrual cycle
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (GFR <30 mL/min) due to potential fluid retention |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C); dose reduction recommended in moderate impairment (Child-Pugh class B: use lowest effective dose) |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established |
| Geriatric use | No specific dose adjustment; caution due to increased risk of thromboembolic events and fluid retention in elderly patients |
| 1st trimester | Contraindicated due to risk of congenital anomalies, particularly cardiovascular and limb defects, and possible association with vaginal adenosis and clear cell adenocarcinoma in female offspring. |
| 2nd trimester | Contraindicated due to potential adverse effects on fetal development, including genitourinary abnormalities. |
| 3rd trimester | Contraindicated due to risk of fetal harm, including possible masculinization of female genitalia and other developmental issues. |
Clinical note
Comprehensive clinical and safety monograph for ENOVID-E (ENOVID-E).
| Placental transfer | Yes; ethinyl estradiol and norethynodrel cross the placenta, with significant transfer documented. |
| Breastfeeding | Excreted into breast milk; may reduce milk production and quality, and potential for adverse effects in nursing infants, such as jaundice and breast enlargement. Use is generally not recommended. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Increased risk of neural tube defects, congenital heart defects, and limb reduction defects due to progestin and estrogen components. Second and third trimesters: Potential for feminization of male fetus, urogenital abnormalities, and possible long-term neurodevelopmental effects. Use contraindicated in pregnancy. |
| Fetal Monitoring | Monitor fetal ultrasound for congenital anomalies if exposed inadvertently. Monitor maternal blood pressure, liver function, and signs of thromboembolism. Assess for fetal growth restriction and urogenital development. |
| Fertility Effects | May suppress ovulation and impair fertility during use. After discontinuation, return to fertility may be delayed but is generally reversible. Long-term use may affect endometrial receptivity. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Use contraindicated in women over 35 years who smoke.
| Serious Effects |
Known or suspected pregnancyThrombophlebitis or thromboembolic disordersBreast cancer (known or suspected)Estrogen-dependent neoplasiaUndiagnosed abnormal genital bleedingLiver disease or impaired liver functionHistory of cholestatic jaundice of pregnancy
| Precautions | Increased risk of thromboembolic disorders, myocardial infarction, stroke, hepatic neoplasia, gallbladder disease, hypertension, and carbohydrate intolerance. Discontinue if jaundice, visual disturbances, or migraine occurs. Monitor blood pressure and liver function. |
| Food/Dietary | No significant food interactions reported. Grapefruit juice may mildly increase estrogen levels but not clinically relevant. Maintain consistent dietary intake to avoid gastrointestinal upset. |
| Clinical Pearls | Enovid-E (5 mg norethynodrel, 0.075 mg mestranol) is a first-generation combined oral contraceptive. Due to high estrogen dose, increased risk of thromboembolism; avoid in smokers over 35 and those with migraine with aura. Typically prescribed for contraception or menstrual disorders. Monitor for breakthrough bleeding and hypertension. |
| Patient Advice | Take one tablet daily at the same time for 21 days, then 7 days off. · Do not smoke while taking this medication, especially if over 35. · Watch for signs of blood clots: sudden leg swelling, chest pain, shortness of breath. · Use backup contraception if you miss a pill, especially during the first week. · This medication does not protect against HIV or other sexually transmitted infections. |
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