ENPRESSE-28
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 382.5 |
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 | Insufficient data in humans; animal studies show risk. Use only if benefit outweighs risk. |
| 2nd trimester | Insufficient data; avoid unless clearly needed. |
| 3rd trimester | May cause fetal harm; avoid in third trimester unless essential. |
Clinical note
Comprehensive clinical and safety monograph for ENPRESSE-28 (ENPRESSE-28).
| Placental transfer | Yes, crosses placenta; documented in animal studies. |
| Breastfeeding | Not recommended during breastfeeding due to potential adverse effects in the infant. |
| Lactation Rating | L4 - Possibly Hazardous |
| 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 | 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. |
■ 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 active substanceSevere hepatic impairmentPregnancy (unless benefit outweighs risk)
| 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. |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided as they inhibit CYP3A4 and can increase ethinylestradiol levels, potentially increasing the risk of estrogen-related adverse effects (e.g., thromboembolism, hypertension). No other specific food interactions are clinically significant. |
| Clinical Pearls | ENPRESSE-28 is a combined oral contraceptive containing ethinylestradiol 0.035 mg and norgestimate 0.18/0.215/0.25 mg in a triphasic regimen. For missed pills, follow the CDC/USMEC guidelines: if one active pill is missed, take it as soon as remembered and continue schedule; if two or more are missed, take the most recent missed pill, discard others, use backup contraception for 7 days, and consider emergency contraception if unprotected intercourse occurred. Monitor for thromboembolic events, especially in smokers over 35, and counsel on increased risk. Concomitant use of certain anticonvulsants (e.g., phenytoin, carbamazepine), rifampin, or St. John's Wort may reduce contraceptive efficacy; consider alternative contraception. Assess for contraindications including migraine with aura, hypertension (>160/100), or history of DVT/PE. |
| Patient Advice | Take one pill daily at the same time each day, starting on the first day of your menstrual period or the Sunday after your period begins as directed. · If you miss a pill, refer to the package insert for instructions; use backup contraception (condoms) if needed and consider emergency contraception if unprotected sex occurred. · Common side effects include nausea, breast tenderness, headache, and breakthrough bleeding; these often improve within a few months. · This medication does not protect against sexually transmitted infections (STIs); use condoms for STI prevention. · Seek medical attention immediately for symptoms of blood clots such as sudden leg pain/swelling, chest pain, shortness of breath, severe headache, or vision changes. · Avoid grapefruit and grapefruit juice while taking this medication as it may increase estrogen levels and side effects. · Inform your healthcare provider of all medications and supplements you take, including St. John's Wort, antibiotics, and anticonvulsants, as they may reduce effectiveness. · Smoking while using this pill increases the risk of serious cardiovascular side effects; do not smoke, especially if you are over 35 years old. |
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