ETHYNODIOL DIACETATE AND ETHINYL ESTRADIOL
Clinical safety rating: avoid
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
Combination hormonal contraceptive: ethynodiol diacetate is a progestin that suppresses gonadotropin secretion (LH and FSH) via negative feedback on the hypothalamic-pituitary axis, inhibiting ovulation; ethinyl estradiol is an estrogen that stabilizes the endometrium and increases cervical mucus viscosity, impeding sperm penetration.
| Metabolism | Ethynodiol diacetate: deacetylated to norethindrone, then hydroxylated and conjugated; ethinyl estradiol: metabolized by CYP3A4, undergoes glucuronidation and sulfation. |
| Excretion | Renal (approximately 40% as metabolites), fecal (approximately 60% as metabolites). Ethynodiol diacetate is extensively metabolized; less than 1% excreted unchanged. |
| Half-life | Ethynodiol diacetate: 12-14 hours; ethinyl estradiol: 13-27 hours (mean ~17 hours). Steady-state achieved after 3-4 days. |
| Protein binding | Ethynodiol diacetate: 95-97% bound to albumin and SHBG; ethinyl estradiol: 98% bound to albumin. |
| Volume of Distribution | Ethynodiol diacetate: Vd not well defined; ethinyl estradiol: Vd ~2-4 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: Ethynodiol diacetate ~71-90% (due to first-pass metabolism); ethinyl estradiol ~40-50%. |
| Onset of Action | Oral: Onset of contraceptive effect with first dose if taken within first 5 days of menses; otherwise 7 days of continuous use required for full effect. |
| Duration of Action | Oral: Contraceptive effect persists for 24 hours. Must be taken daily. Missed doses increase pregnancy risk. |
| Molecular Weight | 472.62 |
1 tablet (1 mg ethynodiol diacetate / 35 mcg ethinyl estradiol) orally once daily for 21 days, followed by 7 placebo days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment (GFR <30 mL/min) due to risk of fluid retention and electrolyte imbalances. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use only if benefits outweigh risks, with monitoring for hepatotoxicity. |
| Pediatric use | Not indicated for use in postmenarcheal adolescents for contraception. In girls >12 years, same adult dosing may be used, but safety and efficacy not established in prepubertal children. |
| Geriatric use | Not indicated in postmenopausal women; no dosing recommendations for elderly. |
| 1st trimester | Contraindicated: risk of fetal harm; non-contraceptive use not recommended. If exposure occurs, evaluate for neural tube defects. |
| 2nd trimester | Contraindicated: associated with fetal abnormalities including cardiac defects and limb reduction. |
| 3rd trimester | Contraindicated: may cause withdrawal bleeding in neonate; potential for long-term effects on reproductive development. |
Clinical note
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
| FDA category | Positive |
| Placental transfer | Crosses the placenta; levels in cord blood are approximately 50% of maternal serum levels. |
| Breastfeeding |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially >35 years) and smoking quantity. Women over 35 who smoke should not use this product.
| Common Effects | osteoporosis prevention |
| Serious Effects |
Current or history of venous thromboembolismCurrent or history of cerebrovascular diseaseCurrent or history of coronary artery diseaseActive liver disease or hepatic tumorsKnown or suspected pregnancyUndiagnosed abnormal genital bleedingKnown or suspected carcinoma of the breast or endometrium
| Precautions | Thrombotic disorders (venous thromboembolism, stroke, MI), hepatic neoplasia, gallbladder disease, hypertension, carbohydrate/lipid effects, headache, irregular bleeding, ectopic pregnancy risk, depression, fluid retention, hereditary angioedema, and chloasma. Discontinue if jaundice, visual disturbances, or sudden neurological symptoms occur. |
Loading safety data…
| Excreted in human milk in small amounts; may reduce milk production and affect infant hormonal balance. Use only if benefit outweighs risk; monitor infant for jaundice and weight gain. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: Increased risk of fetal cardiovascular anomalies, limb defects, and neural tube defects from estrogen exposure. Second/third trimesters: Associated with fetal adrenal suppression, virilization of female fetuses, and potential for hepatic adenoma in offspring. Contraindicated in pregnancy. |
| Fetal Monitoring | Not indicated in pregnancy (contraindicated). If inadvertent exposure occurs: monitor fetal growth, anatomy ultrasound, and neonatal adrenal function. Discontinue immediately if pregnancy suspected. |
| Fertility Effects | Suppresses ovulation via inhibition of gonadotropins (LH, FSH). Reversible upon discontinuation. No long-term impairment of fertility. |
| Food/Dietary |
| No significant food interactions. Grapefruit juice may slightly increase ethinyl estradiol levels but clinical relevance is minimal. Avoid excessive alcohol consumption as it may increase risk of liver toxicity. |
| Clinical Pearls | Ethynodiol diacetate is a first-generation progestin with minimal androgenic activity. Combined with ethinyl estradiol, it is used as a combined oral contraceptive (COC). Monitor for thromboembolic risk, especially in smokers over 35. Advise use of backup contraception if vomiting or severe diarrhea occurs within 3-4 hours of dosing. Assess for drug interactions with CYP3A4 inducers (e.g., rifampin, carbamazepine) which may reduce efficacy. Not recommended for use with other estrogen-containing products. |
| Patient Advice | Take one tablet daily at the same time each day, with or without food. · If you miss a dose, refer to the package instructions or consult your healthcare provider. · Use additional non-hormonal contraception (e.g., condoms) if you miss pills or have vomiting/diarrhea. · Do not smoke while taking this medication, especially if over 35, due to increased risk of blood clots. · Report symptoms of blood clots: sudden chest pain, shortness of breath, leg pain/swelling, or severe headache. · This medication does not protect against HIV or other sexually transmitted infections. |