ENPRESSE-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENPRESSE-28 (ENPRESSE-28).
ENPRESSE-28 is a combined hormonal contraceptive containing ethinyl estradiol and desogestrel. It acts by suppressing gonadotropin release (FSH and LH) from the pituitary, inhibiting ovulation, thickening cervical mucus to impede sperm penetration, and altering the endometrium.
| Metabolism | Ethinyl estradiol is primarily metabolized by CYP3A4; desogestrel is a prodrug converted to its active metabolite etonogestrel, which is further metabolized by CYP3A4, CYP2C9, and CYP2C19. Both undergo extensive first-pass metabolism. |
| Excretion | Primarily renal excretion as unchanged drug (70-80%) and glucuronide conjugate (15-20%); biliary/fecal elimination accounts for <5%. |
| Half-life | Terminal elimination half-life is 18-24 hours, allowing once-daily dosing; steady-state achieved within 5-7 days. |
| Protein binding | 98% bound primarily to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | 0.2 L/kg; indicates distribution primarily in extracellular fluid with minimal tissue binding. |
| Bioavailability | Oral: 40-50%; reduced by high-fat meal (10-20% decrease). |
| Onset of Action | Oral: 1-2 hours for peak serum concentration; clinical antihypertensive effect within 2-4 weeks. |
| Duration of Action | 24 hours per dose; sustained blood pressure reduction over 24 hours with once-daily dosing. |
1 tablet (ethinyl estradiol 0.035 mg / norgestimate 0.25 mg) orally once daily for 21 days, followed by 7 placebo days.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment; contraindicated in patients with renal disease. |
| Liver impairment | Contraindicated in acute hepatic disease or history of cholestatic jaundice with prior oral contraceptive use. No adjustment provided for mild impairment; avoid use in Child-Pugh B or C. |
| Pediatric use | Safety and efficacy not established in females before menarche. Post-menarche: use same dosing as adults (1 tablet daily for 21 days, then 7 placebo days). |
| Geriatric use | Not indicated for use after menopause. No specific geriatric dosing considerations. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ENPRESSE-28 (ENPRESSE-28).
| Breastfeeding | Contraindicated during breastfeeding. Small amounts excreted into breast milk; M/P ratio approximately 0.62. Potential for serious adverse effects in nursing infants, including cardiovascular and renal effects. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: High risk of fetal malformations including craniofacial defects, cardiac anomalies, and neural tube defects. Second and third trimesters: Continued risk of teratogenicity; contraindicated in pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age and with the number of cigarettes smoked, and is quite marked in women over 35 years of age. Women over 35 who smoke should not use combination oral contraceptives.
| Serious Effects |
["Hypersensitivity to any component","Current or history of deep vein thrombosis or pulmonary embolism","Cerebrovascular or coronary artery disease (current or history)","Thrombogenic valvular or rhythm disorders (e.g., atrial fibrillation)","Uncontrolled hypertension (BP >160/100 mmHg)","Major surgery with prolonged immobilization","Diabetes mellitus with vascular involvement","Headaches with focal neurological symptoms or migraine with aura (age ≥35)","Current or history of breast cancer or other estrogen-sensitive neoplasia","Active liver disease or history of liver tumors (benign or malignant)","Undiagnosed abnormal uterine bleeding","Pregnancy (known or suspected)","Cocarcinogenicity with hepatitis C drugs containing ombitasvir/paritaprevir/ritonavir (increased ALT elevations)"]
| Precautions | ["Thromboembolic disorders: Venous and arterial thrombotic events, including pulmonary embolism, stroke, and myocardial infarction, especially in smokers and women with risk factors.","Hepatic disease: Discontinue if jaundice or hepatotoxicity develops.","Hypertension: Monitor blood pressure; discontinue if hypertension occurs.","Carcinoma of the breast and reproductive organs: Use with caution in women with a history of breast cancer or hormone-sensitive tumors.","Gallbladder disease: Increased risk of gallbladder disease.","Carbohydrate and lipid metabolism: May impair glucose tolerance and affect lipid levels.","Headache: Evaluate new or worsening migraine patterns.","Hereditary angioedema: Can trigger or exacerbate symptoms.","Depression: Monitor for development or worsening of depression."] |
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| Monitor maternal blood pressure, renal function, and electrolyte levels regularly. Ultrasound to assess fetal growth and anatomy if inadvertent exposure occurs. Fetal heart rate monitoring recommended. |
| Fertility Effects | May reduce fertility in females by inhibiting ovulation. In males, may decrease sperm motility and count. Effects generally reversible upon discontinuation. |