TRI-LEGEST 21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRI-LEGEST 21 (TRI-LEGEST 21).
Combination estrogen-progestin contraceptive; suppresses gonadotropins (FSH, LH), inhibits ovulation, alters cervical mucus and endometrium.
| Metabolism | Ethinyl estradiol: primarily via CYP3A4; levonorgestrel: primarily via CYP3A4 and reduction, conjugation. Both undergo enterohepatic recirculation. |
| Excretion | Renal: approximately 50-60% as metabolites; fecal: approximately 40-50% (ethinyl estradiol and norgestimate metabolites excreted in bile and feces); less than 1% unchanged in urine. |
| Half-life | Ethinyl estradiol: 13-27 hours (mean ~17 hours); norgestimate active metabolite (norelgestromin): 22-36 hours (mean ~28 hours). Steady-state achieved within 5-10 days. |
| Protein binding | Ethinyl estradiol: ~97-98% bound to albumin and sex hormone-binding globulin (SHBG); norelgestromin: ~98% bound to albumin and SHBG. |
| Volume of Distribution | Ethinyl estradiol: 2-4 L/kg; norelgestromin: 2-4 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: approximately 38-48% for ethinyl estradiol due to first-pass metabolism; norgestimate is a prodrug, rapidly deacetylated to norelgestromin with high presystemic conversion. |
| Onset of Action | Oral administration: inhibition of ovulation occurs within 7-10 days of continuous daily dosing (based on hormone level suppression). |
| Duration of Action | Once-daily oral dosing maintains contraceptive efficacy for 24 hours; withdrawal bleed occurs 2-3 days after last active pill. |
One tablet orally once daily for 21 days, followed by 7 tablet-free days. Each tablet contains norgestimate 0.18 mg/ethinyl estradiol 0.025 mg (days 1-7), norgestimate 0.215 mg/ethinyl estradiol 0.025 mg (days 8-14), norgestimate 0.25 mg/ethinyl estradiol 0.025 mg (days 15-21).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Use is contraindicated in severe renal impairment (GFR <30 mL/min) due to potential fluid retention and electrolyte disturbances. |
| Liver impairment | Contraindicated in acute hepatic disease, hepatic adenomas or carcinomas, and Child-Pugh Class B or C cirrhosis (severe hepatic impairment). No dose adjustment recommended for mild hepatic impairment (Child-Pugh Class A) but caution is advised. |
| Pediatric use | Approved for use in postmenarchal females. Dose is same as adult: one tablet orally once daily for 21 days, then 7 days off. Not indicated for premenarchal females. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific geriatric dose adjustments, but elderly women should be evaluated for contraindications such as thromboembolic disease and cardiovascular risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRI-LEGEST 21 (TRI-LEGEST 21).
| Breastfeeding | Small amounts of ethinyl estradiol and levonorgestrel pass into breast milk. The milk-to-plasma (M/P) ratio for levonorgestrel is approximately 0.37. Combined oral contraceptives may reduce milk production and alter milk composition. Use is generally not recommended during breastfeeding, especially in the immediate postpartum period until milk supply is established. Progestin-only contraceptives are preferred. |
| Teratogenic Risk | First trimester: Epidemiologic studies have not found an increased risk of neural tube defects or other major malformations with combined oral contraceptives. Second and third trimesters: Fetal exposure to estrogen and progestin may cause masculinization of female genitalia if ethinyl estradiol/levonorgestrel is used inadvertently. No known association with congenital heart defects or other structural anomalies. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially over 35 years) and with heavy smoking (≥15 cigarettes/day). Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders, cerebrovascular or coronary artery disease, known or suspected breast carcinoma, endometrial carcinoma or other estrogen-dependent neoplasia, undiagnosed abnormal genital bleeding, cholestatic jaundice of pregnancy or jaundice with prior pill use, hepatic adenoma or carcinoma, known or suspected pregnancy, age >35 years and smoking ≥15 cigarettes/day.
| Precautions | Thromboembolic disorders, cardiovascular disease risk, cerebrovascular events, hypertension, gallbladder disease, hepatic neoplasia, impaired liver function, glucose intolerance, lipid effects, headache, irregular bleeding, depression. |
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| Fetal Monitoring | Monitor blood pressure monthly due to potential estrogen-induced BP elevation. Assess for thromboembolic events (deep vein thrombosis, pulmonary embolism) given increased risk in pregnancy. Evaluate for signs of hepatic adenoma (abdominal pain, mass) or gallbladder disease. Perform pregnancy test if pregnancy is suspected. In case of inadvertent use during pregnancy, no specific fetal monitoring is required beyond routine prenatal care. |
| Fertility Effects | No permanent effect on fertility. After discontinuation, return to normal ovulation and fertility is typically immediate or within one to two cycles. There is no evidence of prolonged infertility or increased time to conception following cessation of combined oral contraceptives. |