Buprenorphine

Patients with acute or severe respiratory insufficiency (e.g., severe asthma, COPD exacerbation, respiratory failure) face increased risk from buprenorphine's respiratory depressant effects, even though these are limited by the partial agonist ceiling.

Severe hepatic impairment alters buprenorphine and naloxone metabolism, requiring dose adjustment. A 52-week RCT found hepatic effects though confounded by viral hepatitis and alcohol (Lucas 2014).

Not an absolute contraindication — buprenorphine is used in pregnancy for OUD treatment. However, altered pharmacokinetics require dose adjustment and specialist management. Neonatal abstinence syndrome is a recognized complication.

Concurrent benzodiazepine use is the most clinically significant dangerous combination. Numerous fatalities documented, especially with IV buprenorphine misuse (Megarbane 2006). Risk management protocols exist for clinically necessary co-prescribing, but unsupervised combination is dangerous.

Administration of buprenorphine to a patient with active full agonist opioid presence precipitates severe acute withdrawal. Induction requires adequate time since last full agonist dose or use of microinduction protocols.

MAO inhibitor co-administration with opioids carries risk of serotonergic and adrenergic crisis. No buprenorphine-specific MAOI interaction study identified.