TRIVARIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRIVARIS (TRIVARIS).

How it works

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.

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRIVARIS (TRIVARIS).

Breastfeeding	TRIVARIS is excreted in human breast milk. The milk-to-plasma (M/P) ratio is approximately 1.2. Based on limited data, nursing infants may receive a clinically significant dose, potentially causing adverse effects such as diarrhea, vomiting, or rash. Breastfeeding is not recommended during TRIVARIS therapy and for 2 weeks after the last dose.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to buprenorphine or naloxone. Severe respiratory insufficiency, acute or severe bronchial asthma, gastrointestinal obstruction (e.g., paralytic ileus). Concomitant use of MAOIs or within 14 days.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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TRIVARIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRIVARIS (TRIVARIS).

How it works

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRIVARIS (TRIVARIS).

Breastfeeding	TRIVARIS is excreted in human breast milk. The milk-to-plasma (M/P) ratio is approximately 1.2. Based on limited data, nursing infants may receive a clinically significant dose, potentially causing adverse effects such as diarrhea, vomiting, or rash. Breastfeeding is not recommended during TRIVARIS therapy and for 2 weeks after the last dose.
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.