DEMULEN 1/35-28
Clinical safety rating
cautionComprehensive clinical and safety monograph for DEMULEN 1/35-28 (DEMULEN 1/35-28).
Combination estrogen-progestin contraceptive; suppresses gonadotropin release, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial receptivity.
| Metabolism | Ethinylestradiol undergoes hepatic metabolism via CYP3A4; norethindrone undergoes reduction and conjugation in the liver. |
| Excretion | Renal 50% (metabolites), fecal 50% (biliary elimination of conjugates). |
| Half-life | Ethinyl estradiol: 17.4 ± 5.6 h (terminal); norethindrone: 10.9 ± 1.6 h (terminal); clinically, steady-state achieved within 5-7 days. |
| Protein binding | Ethinyl estradiol: 97-98% bound to albumin; norethindrone: 93% bound to albumin and SHBG. |
| Volume of Distribution | Ethinyl estradiol: 2.3-4.3 L/kg; norethindrone: 4.4 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Ethinyl estradiol: 40-45% (oral; first-pass metabolism); norethindrone: 64-67% (oral). |
| Onset of Action | Oral: 1-2 h for suppression of gonadotropins; maximal contraceptive effect after 7 days of continuous dosing. |
| Duration of Action | Contraceptive protection requires daily dosing; missed pills reduce efficacy within 24-48 h. |
| Molecular Weight | Ethinyl estradiol: 296.4 Da; Ethynodiol diacetate: 384.5 Da |
One tablet (contains 1 mg ethynodiol diacetate and 35 mcg ethinyl estradiol) orally once daily at the same time each day for 21 days, followed by 7 days of placebo or no tablets.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure. |
| Liver impairment | Contraindicated in acute or chronic hepatic dysfunction, including Child-Pugh class A, B, or C. Avoid use if liver function tests are abnormal. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, use same dosing as adults (one tablet orally once daily). |
| Geriatric use | Not indicated for use in postmenopausal women. |
| 1st trimester | Contraindicated due to risk of congenital defects, particularly cardiovascular and limb anomalies, from female sex hormones. |
| 2nd trimester | Contraindicated; may cause fetal harm, though risk is highest in first trimester. |
| 3rd trimester | Contraindicated; use in late pregnancy may increase risk of thromboembolism and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for DEMULEN 1/35-28 (DEMULEN 1/35-28).
| Placental transfer | Both components cross the placenta; ethinyl estradiol has a placental transfer ratio of approximately 0.5-0.8 relative to maternal serum. |
| Breastfeeding | Small amounts of ethinyl estradiol and ethynodiol diacetate are excreted in breast milk. Use may reduce milk production and quality; alternative contraception should be considered. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Increased risk of neural tube defects, cardiovascular anomalies, and oral clefts (OR ~1.3-1.6). Second/third trimester: Androgenization of female fetus (clitoromegaly, labial fusion) due to progestin component; possible association with hypospadias in males with first-trimester exposure. Avoid use in pregnancy. |
| Fetal Monitoring | Monitor blood pressure, liver function, glucose tolerance, and signs of thromboembolism. If exposure occurs, fetal ultrasound for anomalies; consider echocardiogram if first-trimester exposure. |
| Fertility Effects | Reversible suppression of ovulation. Normal fertility returns within 1-3 cycles after discontinuation. No evidence of permanent impairment. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Risk increases with age and smoking intensity. Women over 35 who smoke should not use this product.
| Serious Effects |
Thromboembolic disordersHistory of deep vein thrombosis or pulmonary embolismCerebral vascular or coronary artery diseaseKnown or suspected breast carcinomaUndiagnosed abnormal genital bleedingPregnancyActive liver disease or impaired liver functionKnown or suspected estrogen-dependent neoplasia
| Precautions | Increased risk of thromboembolic disorders, Cerebrovascular disease, Myocardial infarction, Hepatic neoplasia, Gallbladder disease, Hypertension, Carbohydrate/lipid effects, Headache, Uterine bleeding, Ocular lesions, Depression |
| Food/Dietary | No significant food interactions. Grapefruit juice has minimal effect on ethinyl estradiol; no restriction needed. Avoid excessive alcohol, which may impair adherence or increase liver enzymes. St. John's wort reduces contraceptive efficacy and should be avoided. |
| Clinical Pearls | DEMULEN 1/35-28 (ethinyl estradiol 35 mcg + ethynodiol diacetate 1 mg) is a monophasic combined oral contraceptive. Its progestin has mild androgenic activity, which may be less favorable for acne-prone patients compared to third-generation pills. The 28-day pack includes 21 active pills and 7 inert pills. Counsel patients to take at the same time daily; missed pills increase breakthrough bleeding and pregnancy risk. It may be used off-label for cycle control in patients without contraindications. |
| Patient Advice | Take one pill daily at the same time, preferably after dinner to reduce nausea. · If you miss one pill, take it as soon as remembered; if missed more than one, use backup contraception for 7 days. · Smoking increases risk of blood clots; especially dangerous if over 35 and smokes. · Some antibiotics (e.g., rifampin) and antiseizure medications may reduce effectiveness. · Report any signs of blood clot: sudden leg pain/swelling, chest pain, shortness of breath, or sudden severe headache. · Breakthrough bleeding is common in first 3 cycles; if persistent, contact your healthcare provider. · Do not use if pregnant; if pregnancy occurs, stop immediately. |
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