Buprenorphine-Naloxone

• Opioid Use Disorder
• Medication-Assisted Treatment
• Opioid Dependence
• Opioid Withdrawal Management

Buprenorphine/naloxone is a combination medication used for the treatment of opioid use disorder. This formulation combines buprenorphine (a partial opioid agonist) with naloxone (an opioid antagonist) to reduce the potential for misuse while providing effective treatment for opioid dependence.

Mechanism of Action

The combination works through complementary mechanisms. Buprenorphine is a partial mu-opioid receptor agonist that relieves cravings and withdrawal symptoms while producing a ceiling effect on respiratory depression. Naloxone is an opioid antagonist with poor sublingual/oral bioavailability (approximately 3%) but high parenteral bioavailability. When taken sublingually as directed, naloxone contributes minimally to the clinical effect because it is poorly absorbed. However, if the medication is dissolved and injected, naloxone becomes active and precipitates withdrawal, deterring intravenous misuse. This design helps ensure the medication is taken as prescribed.

Available Formulations

Buprenorphine/naloxone is available in several sublingual and buccal formulations. Sublingual tablets come in 2/0.5 mg and 8/2 mg strengths. Sublingual films are available in 2/0.5 mg, 4/1 mg, 8/2 mg, and 12/3 mg strengths. Generic formulations are available. The sublingual administration requires placing the medication under the tongue and allowing it to dissolve completely without chewing or swallowing.

Medical Uses

Buprenorphine/naloxone is FDA-approved for the treatment of opioid use disorder as part of a complete treatment plan that includes counseling and psychosocial support. It is used for both induction and maintenance therapy. The combination is preferred over buprenorphine alone in most cases due to its lower abuse potential. Clinical studies demonstrate that buprenorphine/naloxone significantly reduces illicit opioid use, improves treatment retention, and decreases opioid-related morbidity and mortality.

Dosing Guidelines

Treatment typically begins with induction when the patient is in mild to moderate opioid withdrawal (usually 12-24 hours after last short-acting opioid use or 24-72 hours after last long-acting opioid use). On day 1, a starting dose of 2/0.5 mg or 4/1 mg is given, with additional doses as needed up to 8/2 mg. On day 2, doses may increase to 16/4 mg. Maintenance doses typically range from 16/4 mg to 24/6 mg daily. Single daily dosing is standard, though some patients may benefit from divided doses. Precipitated withdrawal can occur if started too soon.

Important Safety Information

The medication carries a boxed warning regarding serious, life-threatening respiratory depression (especially with benzodiazepines or other CNS depressants), addiction/abuse/misuse potential, and neonatal opioid withdrawal syndrome. Patients should be instructed to keep the medication secure and away from children or others who may misuse it. Precipitated withdrawal occurs if administered before adequate withdrawal from full opioid agonists. Hepatotoxicity has been reported. Do not switch between buccal and sublingual products on a mg-per-mg basis due to different bioavailabilities.

Drug Interactions

CNS depressants (benzodiazepines, alcohol, other opioids, sedatives) significantly increase risk of respiratory depression and death. CYP3A4 inhibitors may increase buprenorphine levels; CYP3A4 inducers may decrease levels. Full opioid agonists will have diminished effect due to buprenorphine's high receptor affinity. Naltrexone blocks buprenorphine effects; a washout period is needed when switching. Serotonergic medications may increase serotonin syndrome risk.

Special Populations

For pregnant women with opioid use disorder, buprenorphine monotherapy (without naloxone) is generally preferred due to limited safety data on naloxone in pregnancy. However, some women may continue buprenorphine/naloxone if they were stable on it before pregnancy. Neonatal opioid withdrawal syndrome should be anticipated. The medication is excreted in breast milk; women on stable doses may breastfeed with monitoring. Safety in pediatric patients has not been established. Elderly patients may need lower doses. Use with caution in hepatic impairment.