DEMULEN 1/50-28
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 376.5 |
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 | Contraindicated due to risk of congenital anomalies (e.g., cardiovascular, limb defects) and potential for early pregnancy loss. |
| 2nd trimester | Contraindicated due to risk of fetal harm; use only if absolutely necessary. |
| 3rd trimester | Contraindicated due to risk of fetal harm, including possible estrogenic effects and withdrawal bleeding in neonates. |
Clinical note
Comprehensive clinical and safety monograph for DEMULEN 1/50-28 (DEMULEN 1/50-28).
| Placental transfer | Ethinyl estradiol and ethynodiol diacetate cross the placenta; ethinyl estradiol has been detected in fetal tissues. |
| Breastfeeding | Estrogen and progestin are excreted in breast milk; may reduce milk production and quality. Use only if benefits outweigh risks. |
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
■ 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 |
PregnancyThrombophlebitis or thromboembolic disorders (current or history)Cerebrovascular or coronary artery diseaseKnown or suspected breast carcinomaEstrogen-dependent neoplasiaUndiagnosed abnormal genital bleedingJaundice or cholestatic jaundice of pregnancy (history)Hepatic adenoma or carcinomaKnown hypersensitivity to components
| 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 |
| Food/Dietary | No significant food interactions. Grapefruit juice may increase estrogen levels, but clinical significance is unclear. Maintain consistent intake of vitamin C-rich foods as they may increase estrogen absorption. Avoid St. John's wort, which reduces contraceptive efficacy. |
| Clinical Pearls | Demulen 1/50-28 is a monophasic combined oral contraceptive containing ethinyl estradiol 50 mcg and ethynodiol diacetate 1 mg. Due to the 50 mcg estrogen dose, it carries an increased risk of venous thromboembolism compared to lower-dose pills; avoid in patients with migraine with aura, hypertension >160/100 mmHg, or age >35 who smoke. The 28-day pack includes 21 active pills and 7 placebo pills; breakthrough bleeding is more common with higher estrogen. Caution with hepatic enzyme inducers like rifampin or anticonvulsants may reduce efficacy. |
| Patient Advice | Take one pill daily at the same time, preferably with food to reduce nausea. · The first 7 days of the first cycle require a backup contraceptive method if not starting on day 1 of menses. · Missed pill: if one active pill is missed, take it as soon as remembered and continue; if two or more active pills are missed, take the last missed pill, skip the others, use backup for 7 days, and consider emergency contraception. · Smoking increases risk of serious cardiovascular side effects; avoid smoking, especially if over 35. · Report symptoms of blood clots: sudden leg pain/swelling, chest pain, shortness of breath, or severe headache. · The 7 placebo pills are for withdrawal bleeding; start next pack on time regardless of bleeding. |
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