Opioid analgesic (partial agonist)
Buprenorphine is an opioid medicine used for the substitution treatment of opioid dependence (such as heroin), as sublingual tablets. It reduces withdrawal symptoms and drug craving, with a ceiling effect that lowers the risk of severe respiratory depression compared with full agonists. It must only be used under prescription and specialist follow-up.
Also known as: buprenorphine
Buprenorphine with sertraline increases the risk of serotonin syndrome.
Concomitant use of opioids with drugs that affect the serotonergic system, such as SSRIs (sertraline), can result in serotonin syndrome, potentially life-threatening; the buprenorphine label reports cases of serotonin syndrome with concomitant opioids and serotonergic drugs and recommends carefully observing the patient, especially at treatment initiation and dose adjustments, and discontinuing buprenorphine if the syndrome is suspected. Symptoms include mental status changes (agitation, hallucinations, coma), autonomic instability (tachycardia, blood pressure lability, hyperthermia) and neuromuscular aberrations (hyperreflexia, incoordination, rigidity).
Buprenorphine + sertraline: risk of serotonin syndrome (opioid + SSRI). Monitor symptoms, especially at initiation and dose adjustments.
Both raise CNS serotonin; buprenorphine also causes respiratory depression that sertraline may mask.
Agitation, fever, tremor, hyperreflexia, clonus.
Signs of severe serotonin excess require immediate withdrawal and supportive care.
Monitor for serotonin excess; titrate doses with caution.
DailyMed/FDA (NIH/NLM) — approved Buprenorphine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=713db2c6-0544-4633-b874-cfbeaf93db89 ; approved Sertraline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=91e24d17-ff0a-449c-9472-b9df74c98456 — with additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Itraconazole increases buprenorphine concentrations, potentiating sedation and respiratory depression.
Buprenorphine is metabolised by CYP3A4, and itraconazole (a potent CYP3A4 inhibitor) can raise its plasma concentrations: the itraconazole label lists buprenorphine (IV and sublingual) among the drugs with documented pharmacokinetic interaction with itraconazole, and the buprenorphine label warns that CYP3A4 inhibitors increase buprenorphine levels, recommending monitoring and, when the inhibitor is discontinued, considering dose adjustment. The combination (e.g. an opioid substitution patient starting an oral antifungal) requires vigilance for sedation, drowsiness, confusion and respiratory depression, especially at initiation; reduce the buprenorphine dose if needed.
Buprenorphine + itraconazole: itraconazole inhibits CYP3A4 and raises buprenorphine levels. Watch for sedation and respiratory depression.
Buprenorphine is metabolised by CYP3A4; inhibition by itraconazole reduces its metabolism.
Signs of opioid overdose: miosis, sedation, bradypnoea.
Persistent respiratory depression requires urgent assessment.
Use with caution; consider dose reduction and sedation monitoring.
DailyMed/FDA (NIH/NLM) — approved Buprenorphine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=713db2c6-0544-4633-b874-cfbeaf93db89 ; approved Itraconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d555fa-787c-40fb-bb7d-b0d4f7318fd0 — with additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol potentiates the CNS-depressant effects of buprenorphine.
Avoid alcohol during treatment.
EMC-UK (MHRA) — approved BuTrans (Buprenorphine) SmPC: https://www.medicines.org.uk/emc/product/7645/smpc
Buprenorphine may cause clinically significant respiratory depression.
Contraindicated in severe respiratory impairment.
EMC-UK (MHRA) — approved BuTrans (Buprenorphine) SmPC: https://www.medicines.org.uk/emc/product/7645/smpc
May precipitate withdrawal in patients dependent on full opioid agonists.
Contraindicated in dependent patients, except in structured programmes.
EMC-UK (MHRA) — approved BuTrans (Buprenorphine) SmPC: https://www.medicines.org.uk/emc/product/7645/smpc
Buprenorphine crosses the placenta; chronic use may cause neonatal withdrawal.
Not recommended unless benefit outweighs risk.
Excreted into breast milk; avoid while breastfeeding.
Advise effective contraception with chronic use.
EMC-UK (MHRA) — approved BuTrans (Buprenorphine) SmPC: https://www.medicines.org.uk/emc/product/7645/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Partial mu-opioid receptor agonist and kappa-opioid receptor antagonist, indicated for the treatment of opioid dependence (sublingual tablets, preferred for induction). Produces typical opioid agonist effects limited by a ceiling effect (including on respiratory depression); prolongs QTc by ≤15 ms in studies. Long half-life (31-35 h) allowing daily dosing.
Partial agonist at the mu-opioid receptor and antagonist at the kappa-opioid receptor. The ceiling effect on subjective effects and respiratory depression distinguishes it from full agonists; in ascending single-dose studies (1-32 mg), for every measure in which the drug produced an effect there was a dose that produced no further effect. Buprenorphine inhibits CYP2D6 and CYP3A4 in vitro, but therapeutic concentrations are not expected to raise clinically relevant interactions.
Sublingual absorption with wide inter-patient variability (low within-subject variability); Cmax and AUC increase linearly with dose between 4-16 mg, although not directly dose-proportional. Mean Cmax of 1.25 ng/mL (2 mg), 2.88 ng/mL (8 mg) and 4.70 ng/mL (16 mg), with Tmax ~1.3-1.8 hours. In subjective effect studies, peak effect occurred after ~100 minutes.
Metabolised by N-dealkylation to norbuprenorphine (mediated primarily by CYP3A4) and by glucuronidation; norbuprenorphine, the major metabolite, can undergo further glucuronidation. Mass balance study: complete recovery of radiolabel in urine (30%) and faeces (69%) within 11 days; in urine, most buprenorphine and norbuprenorphine is conjugated. Approximately 96% protein bound (alpha and beta globulin).
Mean plasma elimination half-life of 31 to 35 hours after sublingual administration (31.7 h at 2 mg; 35.0 h at 8 mg; 36.5 h at 16 mg); norbuprenorphine has a half-life of ~39-44 hours. In moderate/severe hepatic impairment Cmax, AUC and half-life increase (up to +57% in half-life in severe impairment).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
