TRIVORA-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIVORA-28 (TRIVORA-28).
Combination oral contraceptive; suppresses gonadotropin release (FSH, LH) via estrogen (ethinyl estradiol) and progestin (levonorgestrel), preventing ovulation; increases cervical mucus viscosity, inhibiting sperm penetration; alters endometrial receptivity.
| Metabolism | Ethinyl estradiol: primarily via CYP3A4; levonorgestrel: primarily via CYP3A4, also undergoes glucuronidation. |
| Excretion | Renal (primary): 70% as metabolites (glucuronide and sulfate conjugates); biliary/fecal: 30%. |
| Half-life | Ethinyl estradiol: 13-27 hours (mean 17 hours); norgestimate: active metabolite norelgestromin ~28 hours; levonorgestrel: ~20 hours. Supports daily dosing. |
| Protein binding | Ethinyl estradiol: 97-98% bound to albumin; norgestimate metabolites: 97-99% bound to sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Ethinyl estradiol: 2.0-3.0 L/kg; norgestimate: 2.0-3.0 L/kg (large Vd indicates extensive tissue distribution). |
| Bioavailability | Oral: Ethinyl estradiol ~38-48% (first-pass metabolism); norgestimate: prodrug, rapidly hydrolyzed to norelgestromin with high oral bioavailability. |
| Onset of Action | Oral: Contraceptive effect achieved after 7 consecutive days of administration if started on day 1 of menstrual cycle. |
| Duration of Action | 24 hours; requires daily dosing to maintain contraceptive efficacy. |
One tablet containing 0.05 mg levonorgestrel and 0.03 mg ethinyl estradiol (first 21 tablets) and 7 inert tablets, taken orally once daily for 28 days, with 21 active followed by 7 placebo days.
| Dosage form | TABLET |
| Renal impairment | No specific dosing adjustment provided in FDA labeling; use with caution in patients with renal impairment due to potential fluid retention. |
| Liver impairment | Contraindicated in patients with acute hepatitis, hepatic tumors, or impaired liver function (Child-Pugh class A, B, or C). |
| Pediatric use | Safety and efficacy not established in prepubertal females; after menarche, dosing is same as adult (one active tablet daily for 21 days then 7 placebo). |
| Geriatric use | Not indicated for postmenopausal women; no specific geriatric dosing. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIVORA-28 (TRIVORA-28).
| Breastfeeding | Combination oral contraceptives can reduce milk production and quality. The M/P ratio for ethinyl estradiol is approximately 0.1-0.2; for levonorgestrel, approximately 0.3-1.0. Small amounts of hormones are excreted in breast milk. Use during breastfeeding should be delayed until infant is weaned or after 6 months postpartum if infant is exclusively breastfed, as per CDC and WHO guidelines. Alternative progestin-only methods are preferred. |
| Teratogenic Risk | Trivora-28 is a combination oral contraceptive containing ethinyl estradiol and levonorgestrel. First trimester: No increased risk of major birth defects from inadvertent use, but pregnancy is contraindicated. Second and third trimesters: Not indicated for use; prolonged exposure may be associated with adverse fetal effects including feminization of male fetuses (based on animal data) and potential for metabolic disturbances. Overall risk is low with inadvertent early exposure, but full avoidance is recommended. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Use in women over 35 who smoke is contraindicated.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders (current or history).","Cerebrovascular or coronary artery disease (current or history).","Known or suspected breast cancer or estrogen-dependent neoplasia.","Undiagnosed abnormal genital bleeding.","Pregnancy or suspected pregnancy.","Liver tumor (benign or malignant) or liver disease (active).","Age >35 and smoking ≥15 cigarettes/day.","Hypersensitivity to any component."]
| Precautions | ["Increased risk of thromboembolic disorders (e.g., DVT, PE, MI, stroke).","Discontinue if jaundice, visual disturbances, or migraine occurs.","Hepatic neoplasia risk (benign/malignant liver tumors).","Elevated blood pressure.","Gallbladder disease.","Carbohydrate/lipid metabolism effects.","Retinal thrombosis; discontinue if sudden vision loss.","Depression."] |
Loading safety data…
| Fetal Monitoring | If inadvertent use occurs during pregnancy, no specific monitoring beyond routine antenatal care is required. However, if used in pregnancy (contraindicated), monitor for signs of maternal thromboembolism, hypertension, hepatic dysfunction, and fetal growth parameters. No specific fetal monitoring mandated. |
| Fertility Effects | Trivora-28 suppresses ovulation by inhibiting gonadotropin release. After discontinuation, fertility typically returns rapidly. No permanent adverse effects on fertility are expected. Return to ovulatory cycles may be delayed in some women, but there is no evidence of long-term impairment. |