DEMULEN 1/35-28
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEMULEN 1/35-28 (DEMULEN 1/35-28).
| Breastfeeding | Excreted in breast milk; estimated infant dose <1% of maternal dose. M/P ratio not available for ethinyl estradiol/ethynodiol diacetate. May reduce milk production and quality. Use only if benefits outweigh risks; lowest effective dose recommended. |
| 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. |
■ 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 |
["Known or suspected pregnancy","Current or past thrombosis","Cerebrovascular or coronary artery disease","Valvular heart disease with complications","Severe hypertension","Diabetes with vascular involvement","Headaches with focal neurological symptoms","Major surgery with prolonged immobilization","Known or suspected breast cancer","Endometrial cancer or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenomas or carcinomas","Active liver disease","Known hypersensitivity to any component"]
| Precautions | ["Increased risk of thromboembolic disorders","Cerebrovascular disease","Myocardial infarction","Hepatic neoplasia","Gallbladder disease","Hypertension","Carbohydrate/lipid effects","Headache","Uterine bleeding","Ocular lesions","Depression"] |
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| 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. |