DEMULEN 1/50-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEMULEN 1/50-28 (DEMULEN 1/50-28).
Combination oral contraceptive: Ethinyl estradiol and ethynodiol diacetate suppress gonadotropin secretion (LH, FSH) via negative feedback, inhibiting ovulation. Ethynodiol diacetate also increases cervical mucus viscosity and induces endometrial changes.
| Metabolism | Ethinyl estradiol: CYP3A4; undergoes first-pass metabolism with sulfation and glucuronidation. Ethynodiol diacetate: Deacetylated to norethynodrel, then extensively metabolized via reduction and conjugation. |
| Excretion | Ethinylestradiol and ethynodiol diacetate are extensively metabolized; urinary excretion accounts for ~40% of ethinylestradiol metabolites and ~50-60% of ethynodiol diacetate metabolites; fecal excretion accounts for ~30% of ethinylestradiol metabolites and ~35% of ethynodiol diacetate metabolites; biliary excretion contributes to enterohepatic circulation. |
| Half-life | Ethinylestradiol: terminal elimination half-life ~13-27 hours (mean ~17 hours); ethynodiol diacetate (as norethindrone): terminal elimination half-life ~8-11 hours; clinical context: achieved steady-state within 5-10 days; accumulation not significant due to dose interval. |
| Protein binding | Ethinylestradiol: >97% bound, primarily to albumin, with ~2% bound to sex hormone-binding globulin (SHBG); ethynodiol diacetate (as norethindrone): ~95% bound, primarily to albumin and SHBG. |
| Volume of Distribution | Ethinylestradiol: Vd ~2-4 L/kg; distributes extensively into body tissues; ethynodiol diacetate (as norethindrone): Vd ~4 L/kg; indicates wide distribution including reproductive tissues. |
| Bioavailability | Oral: ethinylestradiol bioavailability ~40-60% due to first-pass metabolism; ethynodiol diacetate bioavailability ~60-80% after oral administration. |
| Onset of Action | Oral: contraceptive effect requires consistent daily dosing for at least 7 days to fully suppress ovulation; onset of serum hormone changes within hours of first dose. |
| Duration of Action | Oral: 24-hour dosing interval; one tablet daily for 28 days (21 active + 7 placebo); ovulation suppression persists only with continued dosing; missed doses increase contraceptive failure risk. |
One tablet orally once daily for 28 consecutive days per cycle.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. Use is not recommended in patients with severe renal impairment due to potential adverse effects. |
| Liver impairment | Contraindicated in patients with Child-Pugh C cirrhosis. For Child-Pugh A or B, use is generally not recommended; if used, monitor closely for adverse effects. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults: one tablet orally once daily for 28 days per cycle. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dose adjustment recommended for elderly, but consider increased risk of thromboembolic disorders. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEMULEN 1/50-28 (DEMULEN 1/50-28).
| Breastfeeding | Contraindicated during breastfeeding. Estrogens reduce milk production and quality. M/P ratio not established; ethinyl estradiol and norgestrel are excreted in breast milk in small amounts, potentially causing adverse effects in the infant. |
| Teratogenic Risk | Contraindicated in pregnancy. First trimester: increased risk of neural tube defects, congenital heart defects, and limb reduction defects from progestins. Second and third trimesters: association with masculinization of female fetus, adrenal suppression, and possible long-term metabolic effects. Estrogen component may increase risk of VACTERL anomalies. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events (e.g., myocardial infarction, stroke, thromboembolism). Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease","Known or suspected breast cancer","Endometrial carcinoma or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenoma or carcinoma","Known or suspected pregnancy","Hypersensitivity to any component"]
| Precautions | ["Thromboembolic disorders (DVT, PE, stroke, MI)","Hepatic neoplasia (benign/malignant liver tumors)","Increased risk of gallbladder disease","Hypertension","Carbohydrate/lipid metabolic effects","Ocular disturbances (retinal thrombosis, optic neuritis)","Depression","Fetal harm if used during pregnancy"] |
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| Fetal Monitoring | Pregnancy test before initiation; rhythm method not required as drug is for contraception. If pregnancy suspected, discontinue immediately and confirm with ultrasound. Monitor for thromboembolic events, hypertension, glucose tolerance, and hepatic function. Fetal monitoring if accidental exposure: detailed anatomy ultrasound, echocardiogram. |
| Fertility Effects | Temporary decrease in fertility while taking; rapid return to baseline fertility upon discontinuation. No permanent negative impact on fertility. |