Table 4

Opioid use disorder (OUD) medications39–43 47

	Methadone (dolophine, methadose)	Buprenorphine±naloxone (Subutex buprenorphine sublingual tablets; Suboxone buprenorphine/naloxone sublingual film for sublingual or buccal use)	Naltrexone (ReVia tablets, Vivitrol injection)
Mu-opioid receptor activity	Synthetic, full agonist	Buprenorphine: partial agonist with high-affinity binding Naloxone: non-selective and competitive opioid receptor antagonist with the high affinity for the mu receptors	Pure, full competitive opioid antagonist with the highest affinity for the mu receptors
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	Buprenorphine: partial kappa receptor agonist or functional antagonist (possibly with antidepressant effects) Weak delta antagonist	Modifies the hypothalamic-pituitary-adrenal axis to suppress alcohol consumption
Clinical considerations	Stimulation of the mu receptor causes euphoria, analgesia, constipation, and respiratory depression	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	Due to naltrexone being a high-affinity opioid antagonist, it blocks the euphoric effects if other opioids are used
FDA-approved formulations	Oral solution, dissolvable tablet	Transmucosal buprenorphine/naloxone (Suboxone, Bunavail, Zubsolv) Injectable buprenorphine (Sublocade)	Oral tablets Extended-release intramuscular injection (Vivitrol)
Dosing	Oral: 10–30 mg/day; titrated up to 80–100 mg/day as tolerated	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
Setting	Licensed outpatient treatment program	Any medical setting; x-waiver required if prescribing outside the inpatient setting	Any medical setting
Additional benefits	Use in comorbid pain, high potency, high structure of delivery setting; low risk of precipitating withdrawal symptoms	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
Adverse effects	Respiratory depression Constipation QTc prolongation Hypoglycemia Hypotension	Headache Insomnia Diaphoresis Nausea/Vomiting Constipation Abdominal pain Infection with the implant Sedation, especially when combined with alcohol and benzodiazepines	Headache Insomnia Unintended precipitation of opioid withdrawal Accidental opioid overdose Depression Suicidality Nausea/Vomiting/Diarrhea Hepatic enzyme abnormalities Nasopharyngitis Injection-site reactions
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
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
Pharmacokinetics	Oral bioavailability: 36%–100% Onset of action: Oral: 0.5–1 hours Intravenous: 10–20 min Metabolized in the liver by CYP2B6 (major), CYP3A4 (major), CYP2D6 (minor), CYP2C19 (minor), and CYP2C9 (minor) Half-life: Children: 19.2+13.6 hours Adults: 8–59 hours Excreted as metabolites by the kidneys and in the bile	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 Buccal film: 27.6+11.2 hours SL tablet: 37 hours Transdermal patch: 26 hours Excreted in the feces and urine	Oral bioavailability: 5%–40% Duration of action: Oral 50 mg: 24 hours Oral 100 mg: 48 hours Oral 150 mg: 72 hours Intramuscular: 4 weeks Metabolized by non-cytochrome-mediated dehydrogenase conversion to 6-beta-naltrexol (primary metabolite) and minor metabolites and glucuronide conjugates Half-life adults: Oral: 4 hours Intramuscular: 5–10 days Excreted in the urine

CNS, central nervous system; FDA, Food and Drug Administration; GI, gastrointestinal; SL, sublingual.