buprenorphine

General Information

Buprenorphine is a partial opioid agonist used to treat opioid use disorder (OUD). It reduces withdrawal symptoms and cravings and is intended to be used as part of a comprehensive treatment plan that includes counseling and psychosocial support (label/guideline).

Buprenorphine induction timing is clinically central: starting too soon after recent opioid use can trigger precipitated withdrawal. Labeling recommends initiating when there are objective signs of moderate opioid withdrawal (label).

Sublingual buprenorphine tablets do not contain naloxone and labeling positions them as preferred for induction. For unsupervised maintenance, buprenorphine/naloxone is commonly preferred because naloxone can deter injection misuse (label/clinical).

Respiratory depression can occur, particularly with concurrent CNS depressants. Many clinicians incorporate opioid overdose risk review and take-home naloxone access planning into routine OUD care (label/clinical).

The compare view, buprenorphine evidence feed, and buprenorphine print page support shared decision-making in settings with comorbid anxiety, sleep disruption, or co-prescribed sedatives.

The buprenorphine monoproduct is commonly used for induction and for selected maintenance scenarios when naloxone-containing formulations are not tolerated. For many stable patients in outpatient care, the buprenorphine/naloxone combination is preferred for unsupervised maintenance (label/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Buprenorphine is a partial agonist at the μ-opioid receptor and has high receptor affinity. Partial agonism can reduce withdrawal/cravings while producing a ceiling effect on some opioid effects; however, it still carries clinically meaningful overdose risk, especially with other CNS depressants (label/clinical).

High receptor affinity is clinically relevant in two directions: (1) it can precipitate withdrawal when started too soon after full agonists, and (2) it can make naloxone reversal more challenging in some overdoses, requiring repeated dosing and emergency support (label/clinical).

• Partial μ-opioid receptor agonism with high receptor affinity (label).

Metabolism and Pharmacokinetics

• Buprenorphine undergoes N-dealkylation to norbuprenorphine (primarily via CYP3A4) and glucuronidation; both buprenorphine and norbuprenorphine have conjugated metabolites (label).
• A mass balance study recovered radiolabel largely in feces (~69%) and urine (~30%) over 11 days, reflecting extensive metabolism and mixed renal/fecal elimination pathways (label).
• After sublingual administration, the label reports a mean elimination half-life range of ~31 to 35 hours (label).
• Buprenorphine is highly protein bound (~96%). Moderate-to-severe hepatic impairment can increase exposure and prolong half-life, so dosing and monitoring are often adjusted (label/clinical).

Dosing and Administration

• Buprenorphine sublingual tablets are administered sublingually as a single daily dose (label).
• For short-acting opioids, the label recommends administering the first dose only when objective and clear signs of moderate opioid withdrawal are present and not less than 4 hours after the last opioid use (label).
• During induction, dosing may be given in 2 mg to 4 mg increments based on symptoms, with the goal of achieving an adequate dose as rapidly as possible while maintaining safety (label/clinical).
• After induction and stabilization, the label describes a maintenance dose range of 4 mg to 24 mg buprenorphine per day, with a target dosage of 16 mg once daily; doses above 24 mg have not shown additional clinical advantage (label).
• When transitioning from methadone, labeling notes higher precipitated withdrawal risk at higher methadone doses (>30 mg) and when the first buprenorphine dose is given shortly after the last methadone dose; plans are often individualized, particularly when fentanyl exposure is present (label/clinical).

Monitoring & Labs

• Confirm objective withdrawal prior to induction to reduce precipitated withdrawal risk; document the induction plan and follow-up schedule (label/clinical).
• Monitor sedation and respiratory risk, especially when alcohol, benzodiazepines, or other sedatives are present; opioid overdose education and naloxone access planning are common (label/clinical).
• Track cravings, ongoing opioid use, and functional outcomes; adjust the treatment plan if goals are not being achieved (label/clinical).
• Monitor for oral/dental adverse effects and reinforce rinsing/oral hygiene practices recommended in labeling (label/clinical).

Follow-up intensity is commonly individualized based on stability, safety, and diversion risk, especially during early treatment (label/clinical).

Adverse Effects

Interactions

• CNS depressants (benzodiazepines, alcohol, sedatives) can increase the risk of respiratory depression when combined with buprenorphine (label/clinical).
• CYP3A4 inhibitors may increase buprenorphine levels and CYP3A4 inducers may reduce levels, affecting withdrawal control and opioid effects; regimen review matters when strong inhibitors/inducers are present (label/clinical).
• Buprenorphine’s receptor affinity can reduce the efficacy of full opioid agonists for analgesia; perioperative and acute pain management often requires proactive planning (clinical).

Other Useful Information

• Evidence syntheses support buprenorphine maintenance for improving retention and reducing illicit opioid use compared with placebo/no medication, with methadone often showing higher retention at adequate doses (review).
• Guidelines emphasize that medication for opioid use disorder (MOUD) is typically long-term and is most effective when paired with follow-up, psychosocial supports, and harm-reduction planning (guideline/clinical).
• In psychiatric practice, common co-occurring issues include anxiety, insomnia, trauma, and co-prescribed sedatives; integrated care often focuses on minimizing sedative stacking and monitoring respiratory risk (clinical).

References

1. Buprenorphine Sublingual C III Tablet Prescribing Information — DailyMed (2024)
2. The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update — Journal of Addiction Medicine (2020)
3. TIP 63: Medications for Opioid Use Disorder — SAMHSA (2021)
4. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence — Cochrane Database of Systematic Reviews (2014)