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. |
| Molecular Weight | Ethinyl estradiol: 296.4 Da; Levonorgestrel: 312.4 Da |
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 | Contraindicated. Increased risk of limb reduction defects and congenital anomalies. |
| 2nd trimester | Contraindicated. Risk of fetal harm, including potential estrogenic effects. |
| 3rd trimester | Contraindicated. Use may cause precocious puberty or other hormonal effects in the fetus. |
Clinical note
Comprehensive clinical and safety monograph for TRIVORA-28 (TRIVORA-28).
| Placental transfer | Ethinyl estradiol (EE) and levonorgestrel (LNG) cross the placenta. EE: ~1-2% transfer; LNG: significant transfer with fetal/maternal ratio ~0.5-1.0. |
| Breastfeeding | Excreted in human milk. May reduce milk production and affect infant hormone levels. Generally not recommended during breastfeeding. Use only if essential. |
| Lactation Rating |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Use in women over 35 who smoke is contraindicated.
| Serious Effects |
PregnancyHistory of or current thromboembolic disordersCerebrovascular or coronary artery diseaseKnown or suspected carcinoma of the breastEstrogen-dependent neoplasiaUndiagnosed abnormal genital bleedingSevere hepatic impairmentKnown hypersensitivity to components
| 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. |
| Food/Dietary | Avoid grapefruit juice as it may increase estrogen levels. No other specific food restrictions. Alcohol in moderation (up to 1 drink/day) is generally acceptable; binge drinking may increase risk of liver toxicity and impair metabolism. |
Loading safety data…
| L5 (Contraindicated) or Avoid |
| 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. |
| 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. |
| Clinical Pearls | Trivora-28 is a triphasic combination oral contraceptive (COC) containing levonorgestrel and ethinyl estradiol. The pill pack has 21 active pills (6 white, 5 light blue, 10 dark blue) followed by 7 ferrous fumarate placebo pills (green). Patients must take pills in the correct order to maintain hormone dose variation. If a dose is missed, follow manufacturer guidelines: if missed one active pill, take as soon as remembered and next pill at usual time; if missed 2 active pills in week 1 or 2, take 2 pills on the day remembered and 2 the next day, then one per day; if missed 2 pills in week 3 or 3 or more pills, skip the remaining active pills and start a new pack on day 7 after last active pill. Non-hormonal backup contraception is needed if pills are missed. COCs increase risk of venous thromboembolism (VTE) and should be avoided in women over 35 who smoke or have migraine with aura, hypertension, or history of VTE. Check for drug interactions with rifampin, antiepileptics, and certain antibiotics. Trivora-28 can be used for cycle control and dysmenorrhea, but not typically for emergency contraception due to lower estrogen dose per pill. |
| Patient Advice | Take one pill daily at the same time, especially the active pills. · Follow pill pack order: white (days 1-6), then light blue (days 7-11), then dark blue (days 12-21), then green placebo (days 22-28). · If you miss a pill, refer to the package insert or call your healthcare provider for instructions on missed doses and use backup contraception (e.g., condoms) if needed. · This medication does not protect against HIV or other sexually transmitted infections. · Common side effects include nausea, breast tenderness, headaches, and spotting, especially in the first few months. · Seek medical attention if you experience symptoms of a blood clot: sudden chest pain, shortness of breath, leg pain or swelling, or severe headache. · Avoid smoking while taking this medication, especially if over 35 years old. · Inform your doctor about all medications you take, including prescription, OTC, and herbal products (e.g., St. John's Wort). |