TRIVARIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIVARIS (TRIVARIS).
TRIVARIS combines an opioid agonist-antagonist (buprenorphine) and a mu-opioid receptor antagonist (naloxone). Buprenorphine partially binds to mu-opioid receptors, reducing withdrawal and craving, while naloxone precipitates withdrawal if injected, deterring abuse.
| Metabolism | Primarily metabolized via CYP3A4 (buprenorphine) and CYP2D6 (naloxone). Naloxone undergoes extensive first-pass metabolism. |
| Excretion | Renal: 60% unchanged; Biliary/Fecal: 30% as metabolites; 10% minor pathways |
| Half-life | Terminal half-life 12-18 hours; allows twice-daily dosing in chronic therapy |
| Protein binding | 92-95% bound primarily to albumin; also to alpha-1-acid glycoprotein |
| Volume of Distribution | Vd 0.8-1.2 L/kg; suggests extensive tissue distribution with good extravascular penetration |
| Bioavailability | Oral: 85-95% with food slightly decreasing rate; IM: 100% |
| Onset of Action | Oral: 30-60 minutes; IV: 2-5 minutes; IM: 15-30 minutes |
| Duration of Action | Oral: 12-24 hours; IV: 6-12 hours; dose-dependent; caution in renal impairment |
| Molecular Weight | 384.5 |
TRIVARIS 10 mg orally once daily, with or without food.
| Dosage form | INJECTABLE |
| Renal impairment | eGFR 30–89 mL/min: no adjustment; eGFR 15–29 mL/min: 5 mg once daily; eGFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 5 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No dose adjustment required based on age alone; monitor renal function and volume status, start at lower end of dosing range if frail or with multiple comorbidities. |
| 1st trimester | Contraindicated due to teratogenicity (major congenital malformations, especially neural tube defects and cardiovascular anomalies). |
| 2nd trimester | Contraindicated due to risk of fetal toxicity (oligohydramnios, renal impairment). |
| 3rd trimester | Contraindicated due to risk of premature closure of ductus arteriosus and persistent pulmonary hypertension. |
Clinical note
Comprehensive clinical and safety monograph for TRIVARIS (TRIVARIS).
| Placental transfer | Crosses placenta readily; achieves fetal concentrations approximately 50-100% of maternal serum levels. |
| Breastfeeding | Excreted into breast milk in significant amounts; may cause adverse effects in the infant. Discontinue breastfeeding or avoid drug. |
| Lactation Rating |
■ FDA Black Box Warning
Risk of respiratory depression, particularly during initiation and dose escalation. Concomitant use of CNS depressants (e.g., benzodiazepines, alcohol) may lead to profound sedation, respiratory depression, coma, and death.
| Serious Effects |
PregnancyBreastfeedingHypersensitivity to TRIVARISHistory of angioedema with ACE inhibitors or ARBsBilateral renal artery stenosis
| Precautions | Risk of neonatal opioid withdrawal syndrome (NOWS) if used during pregnancy. Adrenal insufficiency, hepatic impairment, QT prolongation, and respiratory depression. Avoid abrupt discontinuation to prevent withdrawal. |
| Food/Dietary | For 15 mg and 20 mg doses, must be taken with food to ensure adequate absorption. No other specific food interactions; avoid grapefruit juice if concomitant CYP3A4/P-gp inhibitors are used, but no major food restriction alone. Avoid alcohol due to additive bleeding risk. |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | TRIVARIS is classified as FDA Pregnancy Category X. In the first trimester, there is a high risk of major congenital malformations including neural tube defects, cardiovascular anomalies, and craniofacial defects. In the second and third trimesters, fetal growth restriction, oligohydramnios, and fetal renal impairment may occur. Use is contraindicated in pregnancy. |
| Fetal Monitoring | Maternal monitoring: Complete blood count with differential every 2 weeks, liver function tests monthly, and renal function tests (serum creatinine, BUN) every 4 weeks. Fetal monitoring: Serial ultrasound for fetal growth and amniotic fluid volume every 4 weeks from 20 weeks gestation; fetal echocardiography at 18-22 weeks if exposure occurred in first trimester. |
| Fertility Effects | In preclinical studies, TRIVARIS caused reversible impairment of spermatogenesis and ovulation suppression in animal models. In humans, decreased sperm count and motility have been reported in males. Menstrual irregularities, including amenorrhea, have been observed in females. These effects are typically reversible upon discontinuation of therapy. |
| Clinical Pearls | TRIVARIS (rivaroxaban) is a direct Factor Xa inhibitor; no routine coagulation monitoring required. Avoid use in patients with mechanical heart valves or antiphospholipid syndrome. For patients with CrCl <15 mL/min, not recommended; for CrCl 15-30 mL/min, use with caution and reduce dose to 15 mg once daily for DVT/PE treatment. Administer 2.5 mg twice daily with food for ACS indications. For DVT/PE treatment, use 15 mg twice daily for 21 days, then 20 mg once daily with food. Discontinue 24 hours prior to neuraxial anesthesia procedures. Protamine is not effective; reversal agent is andexanet alfa. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · Do not stop taking TRIVARIS without talking to your doctor first. · May cause serious bleeding; seek immediate medical help for signs of bleeding (unusual bruising, red/pink/black stools, vomiting blood). · Avoid alcohol and NSAIDs (like ibuprofen, aspirin) unless prescribed; they increase bleeding risk. · Store at room temperature in original packaging. · If you miss a dose of the 2.5 mg strength (taken twice daily), take it as soon as you remember on the same day then resume regular schedule; do not take two doses at once. For other strengths (10, 15, 20 mg), if you miss a dose, take it immediately if on same day; if more than 12 hours late, skip dose and take next at regular time; do not double dose. · For the 15 and 20 mg strengths, take with food. The 2.5 and 10 mg strengths can be taken with or without food. · Keep TRIVARIS out of sight and reach of children. |