ENOVID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENOVID (ENOVID).
Combination estrogen-progestin contraceptive; suppresses gonadotropins (LH, FSH) via negative feedback on hypothalamic-pituitary axis, inhibiting ovulation; increases viscosity of cervical mucus and alters endometrial lining to impair implantation.
| Metabolism | Hepatic via CYP3A4; norethynodrel is metabolized to norethindrone; mestranol is demethylated to ethinyl estradiol; metabolites undergo glucuronidation and sulfation. |
| Excretion | Renal (30-50% as metabolites, <5% unchanged) and fecal (40-60% via bile, mostly as glucuronide conjugates). |
| Half-life | Norethynodrel: 5-12 hours; mestranol: 7-20 hours. Terminal half-life of ethinyl estradiol from mestranol conversion: 10-30 hours. Clinical context: steady-state achieved after 3-5 half-lives (3-5 days). |
| Protein binding | Norethynodrel: 95-97% bound to albumin; mestranol: >95% bound to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Norethynodrel: ~2.0 L/kg; mestranol: ~3.5 L/kg. High Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: 80-100% for norethynodrel; mestranol: 40-60% (first-pass metabolism to ethinyl estradiol). |
| Onset of Action | Oral: 24-48 hours for contraceptive effect (ovulation suppression). Therapeutic effect in endometriosis: 2-4 weeks. |
| Duration of Action | Contraceptive: 24 hours (requires daily dosing). Endometriosis: 3-12 months of continuous therapy. |
Oral, 5 mg daily for 20 days starting on day 5 of menstrual cycle for ovulation inhibition; for endometriosis, 5 mg daily for 15 days increasing to 10 mg daily if breakthrough bleeding occurs.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment guidelines; use with caution in severe renal impairment (GFR <30 mL/min) due to potential fluid retention. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C); in mild to moderate impairment (Child-Pugh A or B), reduce dose by 50% or use alternative therapy. |
| Pediatric use | Not recommended for use in pediatric patients for contraception; for endometriosis in adolescents, dose same as adult adjusted for weight (0.1-0.2 mg/kg/day norethynodrel equivalent, max 5 mg/day). |
| Geriatric use | Not indicated for contraception in postmenopausal women; if used for other indications, monitor for thromboembolic events and electrolyte disturbances; initiate at lowest effective dose (2.5 mg/day). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ENOVID (ENOVID).
| Breastfeeding | Excretion into breast milk occurs; M/P ratio not established. Avoid use during breastfeeding due to potential hormonal effects on infant. Alternative contraception recommended. |
| Teratogenic Risk | First trimester: Risk of fetal cardiovascular defects, neural tube defects, and cleft lip/palate. Second and third trimesters: Possible feminization of male fetuses (hypospadias) and clitoral enlargement in females. Postnatal: Vaginal adenosis and clear cell adenocarcinoma of the vagina/cervix in females exposed in utero. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events; contraindicated in women over 35 who smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders, cerebrovascular or coronary artery disease, known or suspected breast carcinoma, undiagnosed abnormal genital bleeding, pregnancy, known or suspected estrogen-dependent neoplasia, impaired liver function, history of cholestatic jaundice of pregnancy, heavy smoking (>15 cigarettes/day) in women over 35.
| Precautions | Increased risk of thromboembolic disorders (stroke, MI, DVT, PE), hepatic neoplasia, gallbladder disease, hypertension, glucose intolerance, and depression. Discontinue if jaundice or visual disturbances occur. |
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| Fetal Monitoring |
| Monitor blood pressure, liver function, and signs of thromboembolism. For fetal assessment, ultrasound to evaluate for structural anomalies (especially after first-trimester exposure). Consider amniocentesis for chromosomal abnormalities if indicated. |
| Fertility Effects | May suppress ovulation and cause endometrial changes that impair fertility. Fertility typically returns after discontinuation, but transient anovulation may occur. No evidence of permanent fertility impairment. |