SUBOXONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SUBOXONE (SUBOXONE).

How it works

Partial agonist at mu-opioid receptor and antagonist at kappa-opioid receptor; also antagonist at delta-opioid receptor.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4 (N-dealkylation to norbuprenorphine) and to a lesser extent CYP2C8; undergoes glucuronidation.
Excretion	Buprenorphine: ~70% fecal, ~30% renal. Norbuprenorphine: ~70% renal, ~30% fecal.
Half-life	Buprenorphine: 37 hours (range 20-70) due to slow dissociation from mu-opioid receptors; norbuprenorphine: ~30 hours.
Protein binding	Buprenorphine: 96% bound (primarily alpha- and beta-globulins); norbuprenorphine: 97% bound.
Volume of Distribution	Buprenorphine: 4.1 L/kg (high tissue distribution, e.g., brain, liver); norbuprenorphine: 3.2 L/kg.
Bioavailability	Sublingual: 30-55% (due to first-pass metabolism). Buccal: similar to sublingual. IV: 100%.
Onset of Action	Sublingual: 30-60 minutes; peak effect at 1-4 hours. IV: immediate but not clinically used.
Duration of Action	Sublingual: 24-36 hours (dose-dependent); allows once-daily dosing for opioid maintenance.

Classification & Brands

Dosing & administration

Sublingual tablet: Initial dose 2-8 mg buprenorphine/0.5-2 mg naloxone on Day 1; target maintenance 12-16 mg/3-4 mg once daily; maximum 24 mg/6 mg once daily.

Dosage form	FILM
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), use with caution; reduce dose by 50% and monitor for CNS depression.
Liver impairment	Child-Pugh Class A: No adjustment. Class B: Start at lower end of dosing range; titrate slowly. Class C: Avoid use due to risk of precipitated withdrawal or severe toxicity; if necessary, use buprenorphine monotherapy with extreme caution.
Pediatric use	Approved for adolescents ≥16 years: Induction dose 2-8 mg/0.5-2 mg sublingually on Day 1; maintenance 12-16 mg/3-4 mg once daily; maximum 24 mg/6 mg per day. Weight-based dosing not established; use adult dosing adjusted for body size.
Geriatric use	No specific dose adjustment; start at lower end of dosing range (2 mg/0.5 mg) and titrate slowly due to increased sensitivity and risk of falls or cognitive impairment.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SUBOXONE (SUBOXONE).

Breastfeeding	Buprenorphine is excreted in breast milk in low concentrations. Infant dose is estimated at <1% of maternal weight-adjusted dose. M/P ratio: approximately 1.0 for buprenorphine, 0.6 for norbuprenorphine. Benefits of breastfeeding likely outweigh risks if mother is stable on treatment.
Teratogenic Risk	Pregnancy category C. First trimester: Limited human data; animal studies show increased risk of neural tube defects at high doses. Second and third trimesters: Risk of neonatal opioid withdrawal syndrome (NOWS) with chronic use. Overall, risk of untreated opioid addiction outweighs potential teratogenic risks.

Warnings & precautions

■ FDA Black Box Warning

Risk of respiratory depression, particularly during initiation and dose adjustment; potential for abuse and dependence; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; ensure proper patient selection and monitoring.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to buprenorphine or naloxone; severe respiratory insufficiency; acute or severe bronchial asthma; severe hepatic impairment; concurrent use of MAOIs or within 14 days.

Clinical Precautions

Precautions

Respiratory depression (especially with benzodiazepines or alcohol); misuse and diversion potential; QT prolongation; adrenal insufficiency; hepatic impairment; withdrawal precipitation if administered too soon after full agonist opioids; neonatal withdrawal syndrome; risk of overdose in children.

Clinical Tips & Counseling

Drug interactions

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SUBOXONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SUBOXONE (SUBOXONE).

How it works

Partial agonist at mu-opioid receptor and antagonist at kappa-opioid receptor; also antagonist at delta-opioid receptor.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4 (N-dealkylation to norbuprenorphine) and to a lesser extent CYP2C8; undergoes glucuronidation.
Excretion	Buprenorphine: ~70% fecal, ~30% renal. Norbuprenorphine: ~70% renal, ~30% fecal.
Half-life	Buprenorphine: 37 hours (range 20-70) due to slow dissociation from mu-opioid receptors; norbuprenorphine: ~30 hours.
Protein binding	Buprenorphine: 96% bound (primarily alpha- and beta-globulins); norbuprenorphine: 97% bound.
Volume of Distribution	Buprenorphine: 4.1 L/kg (high tissue distribution, e.g., brain, liver); norbuprenorphine: 3.2 L/kg.
Bioavailability	Sublingual: 30-55% (due to first-pass metabolism). Buccal: similar to sublingual. IV: 100%.
Onset of Action	Sublingual: 30-60 minutes; peak effect at 1-4 hours. IV: immediate but not clinically used.
Duration of Action	Sublingual: 24-36 hours (dose-dependent); allows once-daily dosing for opioid maintenance.

Classification & Brands

Dosing & administration

Sublingual tablet: Initial dose 2-8 mg buprenorphine/0.5-2 mg naloxone on Day 1; target maintenance 12-16 mg/3-4 mg once daily; maximum 24 mg/6 mg once daily.

Dosage form	FILM
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), use with caution; reduce dose by 50% and monitor for CNS depression.
Liver impairment	Child-Pugh Class A: No adjustment. Class B: Start at lower end of dosing range; titrate slowly. Class C: Avoid use due to risk of precipitated withdrawal or severe toxicity; if necessary, use buprenorphine monotherapy with extreme caution.
Pediatric use	Approved for adolescents ≥16 years: Induction dose 2-8 mg/0.5-2 mg sublingually on Day 1; maintenance 12-16 mg/3-4 mg once daily; maximum 24 mg/6 mg per day. Weight-based dosing not established; use adult dosing adjusted for body size.
Geriatric use	No specific dose adjustment; start at lower end of dosing range (2 mg/0.5 mg) and titrate slowly due to increased sensitivity and risk of falls or cognitive impairment.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SUBOXONE (SUBOXONE).

Breastfeeding	Buprenorphine is excreted in breast milk in low concentrations. Infant dose is estimated at <1% of maternal weight-adjusted dose. M/P ratio: approximately 1.0 for buprenorphine, 0.6 for norbuprenorphine. Benefits of breastfeeding likely outweigh risks if mother is stable on treatment.
Teratogenic Risk	Pregnancy category C. First trimester: Limited human data; animal studies show increased risk of neural tube defects at high doses. Second and third trimesters: Risk of neonatal opioid withdrawal syndrome (NOWS) with chronic use. Overall, risk of untreated opioid addiction outweighs potential teratogenic risks.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to buprenorphine or naloxone; severe respiratory insufficiency; acute or severe bronchial asthma; severe hepatic impairment; concurrent use of MAOIs or within 14 days.