TRI-LEGEST FE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRI-LEGEST FE (TRI-LEGEST FE).
Tri-Legest FE is a combination oral contraceptive containing ethinyl estradiol and norethindrone acetate. It prevents ovulation by inhibiting gonadotropin release (FSH and LH) and alters cervical mucus and endometrial lining to impede sperm penetration and implantation.
| Metabolism | Ethinyl estradiol is metabolized primarily by CYP3A4; norethindrone acetate is hydrolyzed to norethindrone, which is metabolized by reduction and conjugation (glucuronidation and sulfation). |
| Excretion | Renal: ~60% (metabolites), Fecal: ~30% (metabolites), Biliary: minor (~5% as conjugates) |
| Half-life | Norethindrone: 7-8 hours; Ethinyl estradiol: 18 hours (terminal). Steady-state reached after 7 days; clinical contraceptive efficacy requires consistent dosing. |
| Protein binding | Norethindrone: ~80% bound to SHBG and albumin; Ethinyl estradiol: >95% bound to albumin. |
| Volume of Distribution | Norethindrone: 3-4 L/kg; Ethinyl estradiol: 2-3 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: Norethindrone ~60% (first-pass metabolism); Ethinyl estradiol ~45-55% (first-pass and gut wall metabolism). |
| Onset of Action | Oral: Contraceptive effect begins after 7 days of consistent dosing; requires 7-day interval for full ovulatory suppression. |
| Duration of Action | Oral: 24 hours per active pill; continuous suppression of ovulation maintained with daily dosing. After last active pill, withdrawal bleed occurs within 2-3 days. |
One tablet orally once daily for 28-day cycle: 21 days active tablets (norethindrone/ethinyl estradiol) followed by 7 days placebo. For contraception only.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines exist; use with caution in renal impairment due to potential for fluid retention and hyperkalemia. |
| Liver impairment | Contraindicated in severe hepatic disease or active liver disease (Child-Pugh Class C). Use with caution in mild to moderate impairment (Child-Pugh A/B) without specific dose adjustment. |
| Pediatric use | Not indicated in premenarchal females; after menarche, same dosing as adults but only for contraception after assessment of skeletal maturity. |
| Geriatric use | Not indicated for use in postmenopausal women; no specific dose adjustments in elderly females of reproductive age. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRI-LEGEST FE (TRI-LEGEST FE).
| Breastfeeding | Small amounts of steroids pass into breast milk (M/P ratio unknown, estimated <1%). CHCs may reduce milk production and composition, especially with early postpartum use. Avoid use during lactation; progestin-only methods preferred. Use only if benefits outweigh risks. |
| Teratogenic Risk | Pregnancy category X. Combination hormonal contraceptives (CHCs) are contraindicated in pregnancy. First trimester use may cause small increased risk of limb reduction defects and cardiovascular anomalies; second and third trimester exposure is associated with masculinization of female fetuses due to progestin component. Discontinue immediately if pregnancy occurs. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age, especially in women over 35 years, and with number of cigarettes smoked. Women over 35 who smoke should not use combination oral contraceptives.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected pregnancy","Undiagnosed abnormal genital bleeding","Known or suspected breast cancer","Liver tumors (benign or malignant) or active liver disease","Hypersensitivity to any component","Women over 35 who smoke"]
| Precautions | ["Thrombotic disorders (venous thromboembolism, stroke, myocardial infarction)","Hepatic disease (jaundice, liver tumors)","Hypertension","Gallbladder disease","Carbohydrate and lipid metabolism effects","Headache/migraine","Bleeding irregularities","Depression","Cervical cancer risk"] |
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| Fetal Monitoring | Monitor blood pressure at baseline and periodically. Assess for signs of thromboembolism, hepatic dysfunction, headaches, visual disturbances, and mood changes. She may require close monitoring for hypertension, glucose intolerance, and contraceptive efficacy; pregnancy tests if pregnancy suspected. |
| Fertility Effects | Reversible suppression of ovulation. After discontinuation, return to fertility may be delayed (usually normal within 1-3 months for most, but can be up to 1 year). No permanent adverse effect on fertility. |