Mu-opioid receptor activity | | | |
Other receptor considerations | Some agonist action at the kappa receptor Weak antagonist action at N-methyl-D-aspartate receptor Possible antagonist action at the delta receptor
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Clinical considerations | | Due to buprenorphine being a partial agonist, there is a ceiling effect for the binding of mu receptors, which causes decreased euphoric feelings and respiratory depression Due to high-affinity binding, buprenorphine can displace full agonists from the mu receptor and cause withdrawal symptoms The addition of naloxone to buprenorphine is to help decrease injection misuse. Buprenorphine monotherapy is reserved for patients who are pregnant or have a documented severe reaction to naloxone
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FDA-approved formulations | | Transmucosal buprenorphine/naloxone (Suboxone, Bunavail, Zubsolv) Injectable buprenorphine (Sublocade)
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Dosing | | Transmucosal: 8–16 mg (or equivalent) once daily (or in divided doses) Sublocade (for patients maintained on ≤8 mg/day): 300 mg subcutaneous injection monthly for two doses, then 100 mg/month
| Oral: 25 mg on day 1, then 50 mg/day Vivitrol: 380 mg intramuscular every 4 weeks Patient needs to be opioid free for a minimum of 7–10 days to avoid withdrawal symptoms
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Setting | | | |
Additional benefits | | Safety compared with methadone, use in comorbid pain, dosing flexibility, less structured treatment setting Displaces opioid→precipitated withdrawal
| Low diversion, not an opioid, compliance No physical dependence, verifiable dosing, less stigma, fewer drug-drug interactions, FDA approved for both alcohol and OUD
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Adverse effects | Respiratory depression Constipation QTc prolongation Hypoglycemia Hypotension
| | Headache Insomnia Unintended precipitation of opioid withdrawal Accidental opioid overdose Depression Suicidality Nausea/Vomiting/Diarrhea Hepatic enzyme abnormalities Nasopharyngitis Injection-site reactions
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Contraindications | Significant respiratory depression Acute or severe asthma in an unmonitored setting or in the absence of resuscitative equipment GI obstruction including paralytic ileus Caution in patients with hepatic impairment due to drug accumulation
| Buccal film, intramuscular injection, transdermal patch Significant respiratory depression Acute or severe asthma in an unmonitored setting or in the absence of resuscitative equipment GI obstruction including paralytic ileus
| Current physiological opioid dependence or current use of opioid analgesics (including partial opioid agonists) Acute opioid withdrawal Failure to pass naloxone challenge Positive urine screen for opioids Acute hepatitis or hepatic failure
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Warnings and precautions | CNS depression QTc prolongation Respiratory depression Serotonin syndrome
| CNS depression Respiratory depression Hepatotoxicity QTc prolongation Hypotension
| Hepatotoxicity Accidental opioid overdose Acute opioid withdrawal Eosinophilic pneumonia Hypersensitivity reaction Suicidal ideation/Depression
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Pharmacokinetics | | Bioavailability Buccal film: 46%–65% Intramuscular: 70% SL tablet: 29% Transdermal patch: 15% Onset of action: intramuscular >15 min Metabolized in the liver by CYP3A4 to norbuprenorphine (active metabolite), which then undergoes glucuronidation by UGT1A3 or to a lesser extent is metabolized by glucuronidation by UGT1A1 and UGT2B7 to buprenorphine-3-glucuronide Half-life adults Excreted in the feces and urine
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