TRI-LINYAH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRI-LINYAH (TRI-LINYAH).
Combination hormonal contraceptive: ethinyl estradiol and norgestimate. Suppresses gonadotropin release, inhibiting ovulation; also increases cervical mucus viscosity and alters endometrial morphology.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4, undergoes hydroxylation and conjugation. Norgestimate: rapidly hydrolyzed to norelgestromin and further metabolized by CYP3A4, CYP2C9, and CYP2C19. |
| Excretion | Ethinyl estradiol is excreted in urine (40%) and feces (60%) as glucuronide and sulfate conjugates; norgestimate is primarily eliminated via renal excretion (46%) and fecal excretion (47%) as metabolites. |
| Half-life | Ethinyl estradiol: terminal half-life approximately 17 hours (range 13–27 hours), supporting once-daily dosing; norgestimate's active metabolite norelgestromin: terminal half-life approximately 28 hours. |
| Protein binding | Ethinyl estradiol: ~97% bound to serum albumin; norelgestromin: ~99% bound, primarily to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Ethinyl estradiol: Vd approximately 2–4 L/kg, indicating extensive tissue distribution; norelgestromin: Vd approximately 2.7 L/kg. |
| Bioavailability | Oral bioavailability of ethinyl estradiol: ~55% (with interindividual variability); norgestimate: rapidly and extensively converted to active norelgestromin; absolute bioavailability not reported due to extensive first-pass metabolism. |
| Onset of Action | Oral administration: contraceptive effects require 7 days of continuous dosing to achieve therapeutic serum concentrations; immediate if starting on day 1 of menstrual cycle (no backup needed). |
| Duration of Action | Contraceptive protection maintained for 24 hours post-dose; consistent once-daily dosing required; missed doses reduce efficacy. |
| Molecular Weight | 291.4 |
One tablet orally once daily for 21 days, followed by 7 placebo tablets. Each tablet contains 0.035 mg ethinyl estradiol and 0.180/0.215/0.250 mg norgestimate.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal disease or acute renal failure. |
| Liver impairment | Contraindicated in acute hepatic disease or severe hepatic impairment. For Child-Pugh Class B or C, contraindicated. No data for mild impairment. |
| Pediatric use | Not indicated for females with menarche before age 18. Use same dosing as adults post-menarche. |
| Geriatric use | Not indicated for postmenopausal women. No specific dose adjustments for elderly, but consider increased risk of thromboembolism, cardiovascular disease, and contraindication in women >35 years who smoke 15+ cigarettes daily. |
| 1st trimester | Contraindicated due to risk of congenital malformations including neural tube defects. Pregnancy must be excluded before initiation. |
| 2nd trimester | Contraindicated due to risk of fetal harm; alternative therapy recommended. |
| 3rd trimester | Contraindicated; may cause premature closure of ductus arteriosus and neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for TRI-LINYAH (TRI-LINYAH).
| Placental transfer | Active placental transfer occurs; achieves fetal concentrations similar to maternal levels. |
| Breastfeeding | Excreted into human milk in low amounts; however, potential for serious adverse reactions in nursing infants. Use is contraindicated while breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially >35 years) and with number of cigarettes smoked. Women who use oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
PregnancyBreastfeedingHistory of hypersensitivity to any componentSevere hepatic impairment
| Precautions | Thrombotic disorders (venous and arterial), cigarette smoking, elevated blood pressure, gallbladder disease, carbohydrate/lipid effects, headache, hepatic neoplasia, ocular disturbances, interactions with other drugs. |
| Food/Dietary | No specific food restrictions. Grapefruit juice may have a minor interaction but is not considered clinically significant. Alcohol does not directly affect efficacy, but excessive consumption may impair judgment or increase risk of liver issues. |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | TRI-LINYAH (levonorgestrel/ethinyl estradiol) is contraindicated in pregnancy. First trimester: no increased risk of major birth defects from inadvertent use, but intended use contraindicated. Second and third trimesters: known risks including feminization of male fetuses, cardiovascular and neurologic effects from progestin exposure, and estrogenic effects on fetal development. |
| Fetal Monitoring | Monitor blood pressure at each prenatal visit; assess liver function if signs of cholestasis; monitor glucose tolerance if history of gestational diabetes; ultrasound for fetal development if exposure occurs. |
| Fertility Effects | Temporary suppression of ovulation; normal fertility returns upon discontinuation. No permanent adverse effects on female fertility; no data on male fertility. |
| Clinical Pearls | Tri-Linyah is a combination oral contraceptive containing ethinyl estradiol and norgestimate. It follows a 28-day cycle with 21 active pills and 7 placebo pills. The risk of venous thromboembolism is increased, especially in smokers over 35. Efficacy may be reduced with CYP3A4 inducers such as rifampin or certain anticonvulsants. Missed doses require specific instructions: if one active pill is missed, take as soon as remembered; if two are missed, take two pills daily for two days and use backup contraception. Breakthrough bleeding is common in the first few cycles. Use with caution in patients with migraine with aura, hypertension, or history of cholestatic jaundice. |
| Patient Advice | Take one pill daily at the same time each day, with or without food. · If you miss a pill, follow the package insert instructions: for missed active pills, take as soon as remembered and use backup contraception if necessary. · Smoking increases the risk of serious cardiovascular side effects, especially if you are over 35 years old. Do not smoke while taking this medication. · Contact your healthcare provider if you experience severe headaches, chest pain, leg pain or swelling, vision changes, or jaundice. · Antibiotics (except rifampin) generally do not affect efficacy, but always inform your doctor of all medications you are taking. · Store at room temperature away from moisture and heat. |