TRIVORA-21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIVORA-21 (TRIVORA-21).
Combination of ethinyl estradiol and levonorgestrel suppresses gonadotropin release, inhibiting ovulation, altering cervical mucus to impede sperm penetration, and reducing endometrial receptivity to implantation.
| Metabolism | Ethinyl estradiol undergoes first-pass metabolism via CYP3A4 and conjugation (sulfation, glucuronidation) in the liver and intestinal wall. Levonorgestrel is metabolized by reduction, hydroxylation, and conjugation, primarily via CYP3A4. |
| Excretion | Renal (60%), fecal (40%) as metabolites; glucose and sulfate conjugates of ethinyl estradiol and levonorgestrel are excreted in bile and undergo enterohepatic circulation. |
| Half-life | Ethinyl estradiol: terminal half-life 13-27 hours (mean 17 hours); levonorgestrel: terminal half-life 11-45 hours (mean 25 hours). Clinical context: steady-state achieved after 3-5 half-lives (~3-5 days for ethinyl estradiol, ~5-9 days for levonorgestrel). |
| Protein binding | Ethinyl estradiol: 97-98% bound (primarily albumin); levonorgestrel: 97.5-99% bound (sex hormone-binding globulin, SHBG, and albumin). |
| Volume of Distribution | Ethinyl estradiol: 2.5-4.3 L/kg (large volume due to tissue distribution, especially adipose); levonorgestrel: 1.5-2.0 L/kg (distributes to target organs and adipose). |
| Bioavailability | Ethinyl estradiol: 38-48% (oral) due to first-pass metabolism; levonorgestrel: 95-100% (oral) with minimal first-pass effect. |
| Onset of Action | Oral: contraceptive effect begins after 7 consecutive days of administration; immediate if started on day 1 of menstrual cycle. |
| Duration of Action | The contraceptive effect lasts for the duration of the 21-day cycle; after discontinuation, ovulation suppression persists for 1-2 cycles. |
One tablet orally once daily for 21 days, followed by 7 placebo days.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment or acute renal failure; no dose adjustment for mild-to-moderate impairment. |
| Liver impairment | Contraindicated in acute or chronic hepatocellular disease with abnormal liver function; use not recommended in Child-Pugh A or B; avoid in Child-Pugh C. |
| Pediatric use | Not indicated for use before menarche; postmenarchal adolescents: same as adult dosing. |
| Geriatric use | Not indicated for use after menopause; no specific geriatric dosing available. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIVORA-21 (TRIVORA-21).
| Breastfeeding | Combined hormonal contraceptives (CHCs) are generally not recommended during breastfeeding as they may reduce milk production, especially in early postpartum period. Levonorgestrel and ethinyl estradiol are excreted in breast milk; M/P ratio not well established. Use may affect infant hepatic function and cause jaundice. Progestin-only methods preferred. |
| Teratogenic Risk | Trivora-21 (levonorgestrel and ethinyl estradiol) is contraindicated in pregnancy. First trimester: Use is associated with a small increase in risk of congenital anomalies, particularly cardiovascular and limb defects, though absolute risk remains low. Second and third trimesters: Exposure may increase risk of fetal hepatic adenoma, adrenal dysfunction, and potential for urogenital abnormalities. No evidence of teratogenicity from inadvertent early exposure, but discontinuation recommended upon pregnancy diagnosis. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combined hormonal contraceptive use. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast cancer or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Pregnancy (known or suspected)","Benign or malignant liver tumors (current or history)","Hepatic impairment (acute or chronic)","Hypersensitivity to any component","Age >35 and smoking ≥15 cigarettes/day"]
| Precautions | ["Increased risk of venous thromboembolism (VTE) and arterial thrombosis, especially in smokers, obese patients, and those with thrombogenic mutations.","Elevated blood pressure risk; monitor in hypertensive patients.","Possible increased risk of cervical cancer and breast cancer with long-term use.","Hepatic effects: cholestatic jaundice, liver tumors; discontinue if jaundice develops.","Exacerbation of gallbladder disease, porphyria, SLE, and hereditary angioedema.","Retinal thrombosis; discontinue if unexplained vision loss or proptosis occurs."] |
Loading safety data…
| Fetal Monitoring | Monitor blood pressure, liver function tests (LFTs), and signs of thrombosis. In pregnancy-related use, assess for fetal growth and potential congenital anomalies if inadvertent exposure occurred. No routine fetal monitoring indicated for contraception. |
| Fertility Effects | Suppresses ovulation via inhibition of gonadotropin release. No permanent effect on fertility; return to fertility typically within 1-3 months after discontinuation. May temporarily prolong time to conception. |