What is the recommended approach for using buprenorphine in the management of opioid use disorder?

Buprenorphine for Opioid Use Disorder Management

Buprenorphine should be initiated and continued as the cornerstone of medication-assisted treatment for opioid use disorder, combined with behavioral therapies, and should almost never be discontinued—even in perioperative settings—due to the high risk of relapse and mortality associated with treatment interruption. 1, 2

Core Treatment Approach

Medication Selection and Formulation

• Use the buprenorphine/naloxone combination formulation for unsupervised administration because the naloxone component prevents misuse by crushing and injecting while being poorly absorbed sublingually. 3

• Buprenorphine sublingual tablets are FDA-indicated specifically for opioid dependence treatment and should be used as part of a complete treatment plan including counseling and psychosocial support. 2

• Long-acting injectable buprenorphine (Sublocade) is recommended for patients stabilized on transmucosal buprenorphine, with initial 300 mg monthly doses followed by maintenance doses of 100 mg monthly. 1

Initiation Protocol

• Stabilize patients on 8-24 mg daily of sublingual or buccal buprenorphine for a minimum of 7 consecutive days before transitioning to injectable formulations. 1

• Begin treatment with supervised administration, progressing to unsupervised administration only as clinical stability permits, and demonstrate proper sublingual technique at the first visit. 3

• Ensure patients demonstrate tolerance to buprenorphine before initiating long-acting injectable formulations to minimize risk of precipitated withdrawal. 1

• Fixed dosages of at least 16 mg per day are clearly superior to placebo and as effective as methadone for treatment retention and decreased opioid use. 4

Critical Safety Considerations

Concomitant Benzodiazepine and CNS Depressant Use

• Do not categorically deny medication-assisted treatment to patients taking benzodiazepines or other CNS depressants, as prohibiting treatment poses greater risk of morbidity and mortality from untreated opioid use disorder alone. 2

• Educate all patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, and alcohol as routine orientation to buprenorphine treatment. 2

• Develop strategies to manage prescribed or illicit benzodiazepine use at initiation or if it emerges during treatment, with adjustments to induction procedures and additional monitoring as required. 2

• There is no evidence supporting dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use—if a patient is sedated at dosing time, delay or omit that dose, but do not reduce maintenance dosing. 2

• Cessation of benzodiazepines is preferred in most cases; consider gradual tapering to the lowest effective dose or monitoring in a higher level of care for taper. 2

Respiratory Depression Risk

• Buprenorphine demonstrates a ceiling effect on respiratory depression, making it significantly safer than full opioid agonists. 5

• Life-threatening respiratory depression and death have occurred, particularly with misuse by self-injection or concomitant use of benzodiazepines, other CNS depressants, or alcohol. 2

• Use caution in patients with compromised respiratory function (COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression). 2

Perioperative Management

• Continue buprenorphine therapy perioperatively in almost all cases—discontinuation destabilizes patients with opioid use disorder and significantly increases relapse risk. 6

• Transitioning patients off buprenorphine to full agonist opioids permits free access to opioid receptors for analgesia but dramatically increases the possibility of relapse to substance use disorder. 6

• Expert consensus from the Perioperative Pain and Addiction Interdisciplinary Network strongly recommends maintaining perioperative buprenorphine to improve morbidity and mortality related to substance use disorder stability and perioperative analgesia. 6

Special Populations

Pregnancy

• Medication-assisted therapy with buprenorphine has been associated with improved maternal outcomes in pregnant women with opioid use disorder. 1

• Advise pregnant women of the risk of neonatal opioid withdrawal syndrome (NOWS), which is an expected and treatable outcome of prolonged opioid use during pregnancy. 2

• This risk must be balanced against untreated opioid addiction, which results in continued or relapsing illicit opioid use and poor pregnancy outcomes—discuss the importance and benefits of management throughout pregnancy. 2

Pediatric Safety

• Store buprenorphine safely out of sight and reach of children, as it can cause severe, possibly fatal respiratory depression in children accidentally exposed. 2

• Destroy any unused medication appropriately to prevent unintentional pediatric exposure. 2

Monitoring and Follow-Up

Clinical Monitoring Requirements

• Clinical monitoring appropriate to the patient's level of stability is essential—multiple refills should not be prescribed early in treatment or without appropriate follow-up visits. 2

• Follow-up visits should include documentation of any relapses, reemergence of cravings or withdrawal, random urine drug testing, pill or wrapper counts, and checks of state prescription drug database records. 4

• Sporadic opioid use is not uncommon in the first few months and should be addressed by increased visit frequency and more intensive engagement with behavioral therapies, not treatment discontinuation. 4

• Toxicology screening should test for both prescribed and illicit benzodiazepines to monitor for concomitant use. 2

Drug Interactions

• CYP3A4 inhibitors (macrolide antibiotics, azole-antifungals, protease inhibitors like ritonavir) can increase buprenorphine plasma concentration—consider dosage reduction until stable drug effects are achieved and monitor for respiratory depression and sedation. 2

• CYP3A4 inducers (rifampin, carbamazepine, phenytoin) can decrease buprenorphine plasma concentration—consider increasing dosage until stable drug effects are achieved and monitor for withdrawal signs. 2

• Monitor patients taking atazanavir (with or without ritonavir) closely and reduce buprenorphine dose if warranted, as elevated buprenorphine levels and increased sedation have been reported. 2

Provider Requirements and System Considerations

• Physicians prescribing buprenorphine must have appropriate training and certification, though recent regulatory changes have reduced barriers to prescribing. 1, 7

• Physicians not already certified can undergo training to receive a waiver from the Substance Abuse and Mental Health Services Administration (SAMHSA) to provide buprenorphine in office-based settings. 1

• Physicians prescribing opioids in communities without sufficient treatment capacity for opioid use disorder should strongly consider obtaining this waiver. 1

• Barriers to buprenorphine treatment include lack of institutional support, insufficient resources, and lack of specialty backup—identify treatment resources in the community and work to ensure sufficient treatment capacity. 1

Integration with Comprehensive Care

• All medication-assisted treatments for opioid use disorder must be combined with behavioral therapies for optimal outcomes. 1

• Evidence-based treatment typically includes buprenorphine or methadone in combination with behavioral therapies such as cognitive-behavioral therapy, contingency management, relapse prevention, and motivational enhancement therapy. 6, 1

• Integrated treatment approaches that address substance use disorders alongside other health issues show improved outcomes. 1