FDA Requires Update to Boxed Warning for Benzodiazepines

October 2, 2020

The FDA called for more detailed information on risks associated with benzodiazepine use based on review of adverse event reports dating from 1968.

The “current prescribing information for benzodiazepines does not provide adequate warnings about [the] serious risks and harms associated with these medicines so they may be prescribed and used inappropriately.”

The FDA statement above was made regarding class labeling of benzodiazepines as the agency called for an update to the current Boxed Warning. The revised must include additional information on the risks of abuse, misuse, addiction, physical dependence and withdrawal reactions associated with this drug class.

The requirement for the update is the outcome of an FDA review of postmarketing databases and published literature on benzodiazepine use and these associated risks. The review evaluated 104 cases from the FDA Adverse Event Reporting System (FAERS) database from January 1, 1968 through June 30, 2019, which represented a small subset of FAER cases but identified the most descriptive reports of dependence or withdrawal:

  • 80% of cases described benzodiazepine withdrawal, reported even when the drug was prescribed for therapeutic use
  • Most cases reported use of the agents for months to years.
  • Time to dependence after drug initiation ranged from days to weeks
  • Withdrawal symptoms were found to last from weeks to years.
  • Abrupt discontinuation vs dose tapering was described in some cases; most likely the cause of withdrawal symptoms.

To mitigate the potential for benzodiazepine-related adverse events, the Agency recommends the following: