buprenorphine
Partial opioid receptor agonist· Brands: Temgesic, Subutex, Suboxone, Buprenex, TranstecIMIVSCSLTOP
Mechanism of action
Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. It binds with high affinity to the mu receptor, producing analgesic effects but with a ceiling effect on respiratory depression. Its partial agonist activity can precipitate withdrawal in patients who are opioid-dependent when it displaces a full agonist. It also has a long duration of action due to its slow dissociation from the receptor.
Pharmacokinetics
Buprenorphine is metabolised primarily by N-dealkylation to norbuprenorphine, which is further glucuronidated. It is subject to extensive first-pass metabolism, so oral bioavailability is low; it is commonly given sublingually, where bioavailability improves. It is also available via parenteral and transdermal routes. It is highly protein-bound and undergoes enterohepatic recirculation. Elimination is predominantly in faeces, with renal excretion of metabolites. The mean plasma half-life is around 24 to 42 hours.
Indications & dosing
Opioid use disorder (maintenance treatment)
Starting dose 2-4 mg when withdrawal symptoms appear; titrate to maintenance 8-24 mg daily. Usually combined with naloxone to deter misuse.
- adult · SL: 2–24 mg once daily · Starting dose 2-4 mg when withdrawal symptoms appear; titrate to maintenance 8-24 mg daily. Usually combined with naloxone to deter misuse.
Moderate to severe pain
Partial agonist; ceiling effect on respiratory depression. May precipitate withdrawal in opioid-dependent patients. Use with caution in elderly or hepatic impairment.
- adult · SL: 0.2–0.4 mg every 8-12 hours · Partial agonist; ceiling effect on respiratory depression. May precipitate withdrawal in opioid-dependent patients. Use with caution in elderly or hepatic impairment.
Chronic pain (transdermal)
For moderate chronic pain. Apply to clean, dry, hairless skin; change every 7 days. Not for acute or breakthrough pain.
- adult · TOP: 5–20 mcg/hour every 7 days · For moderate chronic pain. Apply to clean, dry, hairless skin; change every 7 days. Not for acute or breakthrough pain.
Contraindications & precautions
- Severe respiratory insufficiency · Buprenorphine may cause respiratory depression, which could be exacerbated in patients with compromised respiratory function.
- Acute severe asthma · Risk of bronchospasm and worsening respiratory function.
- Paralytic ileus · Opioid-induced constipation may worsen obstruction.
- Hypersensitivity to buprenorphine or any excipient · Cross-sensitivity with other opioids may occur.
- Severe hepatic impairment · Metabolism is hepatic; dose reduction may be required.
- Avoid concurrent use of alcohol and other CNS depressants, as they enhance respiratory depression.
- Monitor respiratory rate, especially during dose titration and in patients with respiratory disease.
- Use with caution in hepatic impairment; consider dose reduction.
- May precipitate withdrawal if administered to patients physically dependent on full opioid agonists.
- Use with caution in the elderly and debilitated patients.
- Seek specialist advice before use in pregnancy and lactation.
Adverse effects
- Sedation
- Dizziness
- Nausea
- Constipation
- Respiratory depressionserious
- Hypotensionserious
- Adrenal insufficiencyserious
- Hepatic enzyme elevationserious
Renal & hepatic adjustment
- eGFR 30–300: No dose adjustment required.
- eGFR 0–29: Use with caution; consider reducing the initial dose and titrating slowly. Monitor for increased adverse effects.
- Hepatic impairment (mild): No dose adjustment required. Use with caution.
- Hepatic impairment (moderate): Reduce the initial dose and titrate slowly. Monitor closely for sedation and respiratory depression.
- Hepatic impairment (severe): Avoid use. (avoid)
Monitoring, pregnancy & toxicity
- Respiratory rate · During initiation and dose titration
- Sedation score · During initiation and dose titration
- Blood pressure · During initiation and dose increases
- Liver function tests · Baseline and periodically during chronic use
- Pain score · Regularly to assess efficacy
- Signs of withdrawal · When discontinuing or reducing dose
- Pregnancy: Buprenorphine may be used in pregnancy for opioid dependence, but it can cause neonatal opioid withdrawal syndrome (NOWS). Specialist supervision is advised.
- Toxicity: Respiratory depression · Naloxone may be required in higher doses due to partial agonist activity; consider continuous infusion and supportive care.
- Toxicity: Miosis · Monitor; supportive measures.
- Toxicity: Sedation · Supportive care; consider naloxone if severe.
- Toxicity: Hypotension · Supportive care, IV fluids, and vasopressors if needed.
Antidotes & reversal
- Naloxone · High receptor affinity - higher-than-usual naloxone doses or infusion may be required.
Clinical notes
Buprenorphine is used for the management of moderate to severe pain, and in the treatment of opioid dependence. It should be used with caution in patients with respiratory impairment, hepatic dysfunction, or biliary disease. The risk of dependence is lower than for full agonist opioids, but it can still occur. Because of its partial agonist activity, buprenorphine may precipitate withdrawal in patients who have been receiving a full agonist for a long time. It is contraindicated in patients who are not opioid-tolerant. The naloxone combination product is used to discourage intravenous misuse.
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BNF; local formulary