TRI-PREVIFEM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRI-PREVIFEM (TRI-PREVIFEM).
Combination oral contraceptive: ethinyl estradiol and norgestimate exert contraceptive effects primarily by suppression of gonadotropin secretion (FSH and LH), thereby inhibiting ovulation. Additionally, progestin induces changes in cervical mucus and endometrial receptivity.
| Metabolism | Ethinyl estradiol is primarily metabolized via CYP3A4; norgestimate is extensively metabolized by hepatic CYP3A4 and other enzymes, undergoing hydrolysis and reduction to active metabolites (norelgestromin, norgestrel). |
| Excretion | Ethinyl estradiol: 40% renal, 60% fecal; norgestimate and its metabolites: 80% renal, 20% fecal. |
| Half-life | Ethinyl estradiol: terminal half-life 13-27 hours; norgestimate: terminal half-life of norelgestromin (active metabolite) 12-30 hours; clinical context: once-daily dosing provides steady-state concentrations within 7-10 days. |
| Protein binding | Ethinyl estradiol: 97-98% bound to albumin; norgestimate/norelgestromin: >99% bound to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Ethinyl estradiol: 3.8-5 L/kg; norelgestromin: 2-3 L/kg; indicates extensive distribution into tissues. |
| Bioavailability | Oral: ethinyl estradiol 38-48%; norgestimate is a prodrug with nearly 100% conversion to active metabolite norelgestromin during first pass; overall oral bioavailability of active metabolites is about 60-70% due to first-pass metabolism. |
| Onset of Action | Oral: contraceptive efficacy begins within 24 hours if started on day 1 of menstrual cycle; therapeutic effects on menstrual cycle regulation occur within first cycle. |
| Duration of Action | Duration of contraceptive protection is 24 hours with daily dosing; requires consistent daily administration to maintain efficacy. |
One tablet (norgestimate 0.180 mg/ethinyl estradiol 0.025 mg) orally once daily for 21 days, followed by 7 days of placebo; repeat cycle.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal insufficiency or acute renal failure due to potential for fluid retention and electrolyte disturbances. |
| Liver impairment | Contraindicated in acute hepatic disease, hepatocellular carcinoma, or Child-Pugh class B or C cirrhosis. For mild hepatic impairment (Child-Pugh A), use with caution; no specific dose adjustment available but monitor liver function. |
| Pediatric use | Not indicated for postmenarcheal adolescents; safety and efficacy established for use after menarche. Dose same as adults: one tablet daily for 21 days, then 7 placebo. |
| Geriatric use | Not indicated for postmenopausal women. No specific dose adjustments for elderly; generally not used in this population due to increased risk of thromboembolic events and contraindication in women over 35 years who smoke. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRI-PREVIFEM (TRI-PREVIFEM).
| Breastfeeding | Enters breast milk in small amounts. M/P ratio unknown. May reduce milk production and content. Not recommended during breastfeeding. |
| Teratogenic Risk | FDA Pregnancy Category X. Contraindicated in pregnancy. First trimester exposure associated with cardiovascular defects and limb reduction defects. Second and third trimester exposure linked to female genital tract abnormalities (e.g., vaginal adenosis, clear cell adenocarcinoma) and urogenital anomalies in male fetuses (e.g., hypospadias). |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives. This risk increases with age and with the number of cigarettes smoked, and is quite marked in women over 35 years of age. Women who use combination oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders, history of deep vein thrombosis or pulmonary embolism, cerebrovascular or coronary artery disease, known or suspected pregnancy, liver tumors (benign or malignant), undiagnosed abnormal genital bleeding, known or suspected carcinoma of the breast or endometrium, hypersensitivity to any component, age >35 and smoking, uncontrolled hypertension, migraine with focal neurological symptoms.
| Precautions | Thrombotic events (including venous thromboembolism, stroke, myocardial infarction), hepatic neoplasia, gallbladder disease, hypertension, carbohydrate/lipid effects, headache, irregular bleeding, depression, interaction with other drugs (e.g., anticonvulsants, antibiotics). |
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| Monitor blood pressure, liver function, glucose tolerance, and signs of thromboembolism. Perform pregnancy test before initiation. Ultrasound monitoring if exposure occurs. |
| Fertility Effects | Normal fertility returns after discontinuation. No permanent effects. Female fertility may be delayed temporarily. |