Table 4

Opioid use disorder (OUD) medications39–43 47

(dolophine, methadose)
(Subutex buprenorphine sublingual tablets; Suboxone buprenorphine/naloxone sublingual film for sublingual or buccal use)
(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)

  • 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

  • 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

  • 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

  • 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.