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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
| FDA category | Positive |
| Breastfeeding | Excreted in breast milk. Estrogen and progestin may reduce milk production and alter composition. M/P ratio: unknown. Use during breastfeeding is not recommended due to potential adverse effects on infant (jaundice, breast enlargement). |
| 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. |
■ 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 |
Thrombophlebitis or thromboembolic disorders (current or history), cerebrovascular or coronary artery disease, known or suspected breast cancer, endometrial carcinoma or other estrogen-sensitive neoplasia, undiagnosed abnormal genital bleeding, known or suspected pregnancy, liver tumors or active liver disease, hypersensitivity to any component, age >35 and smoking, and use with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir.
| 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…
| 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. |