From the Guidelines
Buprenorphine is generally associated with a lower risk of overdose compared to full opioid agonists, but risks still exist, particularly when combined with other central nervous system depressants. When prescribing buprenorphine, clinicians should be aware of the potential risks of overdose, especially during induction or when combined with other substances like benzodiazepines or alcohol 1. The greatest overdose risk occurs during induction when patients may still have other opioids in their system or during periods of decreased tolerance after discontinuation. To minimize these risks, clinicians should:
- Start with appropriate dosing (typically 2-4mg initially, titrating up to maintenance doses of 16-24mg daily)
- Screen for and address polysubstance use
- Educate patients about overdose prevention
- Prescribe naloxone rescue kits
- Ensure close monitoring during the induction phase Patients with liver impairment may require dose adjustments as buprenorphine is metabolized hepatically 1. Despite these risks, evidence consistently shows that being on buprenorphine treatment significantly reduces overall overdose mortality compared to being untreated for opioid use disorder 1. It is essential to weigh the benefits and risks of buprenorphine treatment and to carefully monitor patients to minimize the risk of overdose. Clinicians should also be aware of the guidelines for prescribing opioids, including the CDC Clinical Practice Guideline for Prescribing Opioids for Pain, which recommends starting with the lowest effective dosage and avoiding unnecessary dosage increases 1. By following these guidelines and taking a cautious approach to prescribing buprenorphine, clinicians can help minimize the risk of overdose and provide effective treatment for patients with opioid use disorder.
From the FDA Drug Label
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF BUPRENORPHINE HYDROCHLORIDE INJECTION Addiction, Abuse, and Misuse Because the use of buprenorphine exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient's risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see WARNINGS]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of buprenorphine, especially during initiation or following a dosage increase. Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
The main risks of prescribing buprenorphine and overdose are:
- Addiction, abuse, and misuse: Buprenorphine exposes patients to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death.
- Life-threatening respiratory depression: Serious, life-threatening, or fatal respiratory depression may occur with use of buprenorphine, especially during initiation or following a dosage increase.
- Concomitant use with benzodiazepines or other CNS depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. To minimize these risks, proper dosing and titration of buprenorphine are essential, and patients should be regularly reassessed for the development of addiction, abuse, and misuse behaviors and conditions 2.
From the Research
Risks of Prescribing Buprenorphine and Overdose
- Buprenorphine is considered a safe opioid due to its relatively low maximum effect on respiratory depression, but it can produce serious respiratory depression, particularly when combined with sedatives such as benzodiazepines 3.
- The risk of overdose is increased when buprenorphine is misused or taken in high doses, especially in combination with other psychotropic drugs 4.
- Low dose initiation of buprenorphine is an alternative method that can minimize the risk of precipitated opioid withdrawal and expand the population to which buprenorphine can be offered 5.
- Prescribing decisions, such as the initial dose and days of supply, can impact treatment discontinuation and adverse opioid-related events, with lower initial doses and fewer initial days of supply associated with increased odds of discontinuation and adverse events 6.
Factors Contributing to Overdose Risk
- Combination with sedatives such as benzodiazepines can increase the risk of respiratory depression and overdose 3, 4.
- High-dose buprenorphine can cause severe respiratory depression, especially in situations of abuse or misuse 4.
- The role of norbuprenorphine, the main N-dealkylated buprenorphine metabolite, in contributing to respiratory depression is still unclear 4.
- Pharmacodynamic and pharmacokinetic interactions between buprenorphine and other drugs, such as benzodiazepines, can increase the risk of overdose 4.
Mitigating Overdose Risk
- Low dose initiation of buprenorphine can minimize the risk of precipitated opioid withdrawal and overdose 5.
- Gradually titrating the buprenorphine dose and continuing the full opioid agonist can help reduce the risk of overdose 5.
- Clear communication and frequent monitoring can help identify potential risks and prevent overdose 5.
- Prioritizing care coordination and providing guidance on the use of low dose initiation can help mitigate the risk of overdose 5, 7.