Evidence on Buprenorphine Dose Limits: A Review

J Addict Med. 2023 Sep-Oct;17(5):509-516. doi: 10.1097/ADM.0000000000001189. Epub 2023 Jun 16.

Abstract

Objectives: As overdose deaths from fentanyl continue to increase, optimizing use of medications for opioid use disorder has become increasingly important. Buprenorphine is a highly effective medication for reducing the risk of overdose death, but only if a patient remains in treatment. Shared decision making between prescribers and patients is important to establish a dose that meets each patient's treatment needs. However, patients frequently face a dose limit of 16 or 24 mg/d based on dosing guidelines on the Food and Drug Administration's package label.

Methods: This review discusses patient-centered goals and clinical criteria for determining dose adequacy, reviews the history of buprenorphine dose regulation in the United States, examines pharmacological and clinical research results with buprenorphine doses up to 32 mg/d, and evaluates whether diversion concerns justify maintaining a low buprenorphine dose limit.

Results: Pharmacological and clinical research results consistently demonstrate buprenorphine's dose-dependent benefits up to at least 32 mg/d, including reductions in withdrawal symptoms, craving, opioid reward, and illicit use while improving retention in care. Diverted buprenorphine is most often used to treat withdrawal symptoms and reduce illicit opioid use when legal access to it is limited.

Conclusions: In light of established research and profound harms from fentanyl, the Food and Drug Administration's current recommendations on target dose and dose limit are outdated and causing harm. An update to the buprenorphine package label with recommended dosing up to 32 mg/d and elimination of the 16 mg/d target dose would improve treatment effectiveness and save lives.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Buprenorphine* / therapeutic use
  • Drug Overdose* / drug therapy
  • Fentanyl / adverse effects
  • Humans
  • Narcotic Antagonists / therapeutic use
  • Opioid-Related Disorders* / drug therapy
  • Substance Withdrawal Syndrome* / drug therapy

Substances

  • Buprenorphine
  • Analgesics, Opioid
  • Narcotic Antagonists
  • Fentanyl