FDA 2020 Benzodiazepine Boxed Warning

We encourage those who have not reported their harm to file a MedWatch report so that the FDA is aware of the many problems that remain unaddressed. Learn How to report HERE.

Previous Petition & Boxed Warning

In September 2020, the FDA announced a new boxed warning for benzodiazepines. In 2010, Emily Robin, a patient harmed by benzodiazepines, submitted a Citizen’s Petition requesting a new boxed warning on benzodiazepine packaging and modifications to the prescribing information. More than five years after submission, in 2015, Janet Woodcock, M.D., the FDA’s Principal Deputy Commissioner, responded, rejecting the proposed changes. In 2016, the FDA issued a new boxed warning specifically advising against combining benzodiazepines with opioids, leaving the contents of the Citizen’s Petition unaddressed.

Benzodiazepine Information Coalition’s Call-to-Action

Background

  • In 2017, Benzodiazepine Information Coalition led a community-wide reporting drive through MedWatch, the FDA’s adverse event reporting program.
  • We hoped this drive would encourage the FDA to reexamine benzodiazepine safety.
  • We realized that the FDA’s prescribing literature failed to warn about the real risks of harm that patients are experiencing.
  • Patient support groups joined our call-to-action and urged their members to report their harm.
  • As a result, thousands of patients reported their adverse events.

Our FDA Call-To-Action Worked (Sort of)

  • In 2018, the FDA observed an increase in patient adverse event reports.
  • These reports described prolonged symptoms after benzodiazepine withdrawal and failed attempts at discontinuation.
  • The FDA found that this increase in reporting was likely due to our call-to-action.
  • They investigated and discovered several themes in the reports.

FDA Observed Themes

  • Lack of physician education/knowledge regarding benzodiazepine prescribing
  • Lack of patient education by the physician at the time of prescribing
  • Physician-directed tapering schedules that did not prevent withdrawal symptoms
  • In spite of this, the FDA only produced a memorandum, deciding that existing benzodiazepine warnings were sufficient and that the numerous reports required no regulatory action.

The FDA’s Second Look

The FDA Starts a Review

  • In 2019, shortly after reviewing our call-to-action, the FDA began a review of benzodiazepines.
  • They specifically wanted to explore if Xanax was associated with more abuse and dependence than other benzodiazepines.
  • The FDA reviewed 104 cases of adverse events selected from the roughly 300,000 MedWatch adverse event reports.

FDA Review Findings

  • Adverse benzodiazepine events occur with prescribed therapeutic use.
  • Physician education about benzodiazepine safety is lacking.
  • Withdrawal was longer than expected.
  • The median length of withdrawal symptoms was 9.5 months.
  • Physical dependence occurred within days or weeks.
  • Median onset time to physical dependence was 14 days.
  • Abrupt and over-rapid tapers are harming patients.
  • Protracted withdrawals can last 12 months or more post-cessation.
  • In the longest case in the 104-case series, withdrawal symptoms lasted 8 years and were still present.

The FDA Takes Action

  • In September, 2020, the FDA announced a new benzodiazepine boxed warning.
  • The Warning now includes the risks of:
    • abuse
    • addiction
    • physical dependence
    • withdrawal reactions
  • The FDA now recommends:
    • judicious benzodiazepine prescribing
    • gradual benzodiazepine tapering
    • standardized warning labels on all benzodiazepines
Old Benzodiazepine Boxed Warning
New Benzodiazepine Boxed Warning

Canada Takes Action

  • In October, 2020, following the FDA Boxed Warning announcement, Health Canada also took action and updated their safety labels for benzodiazepines and benzodiazepine-like drugs.
  • The update by Health Canada included warnings about the risks of: 
    • problematic use and substance use disorder
    • severe and life-threatening withdrawal symptoms
    • harm when taken with opioids, which may cause deep drowsiness, respiratory depression, coma and death
    • falls and fractures in specified populations

The Benzodiazepine Boxed Warning Remains an Incomplete Achievement

Unaddressed Problems Remain

  • Many problems were not addressed in the warning, including:
    • No help for harmed patients
    • No help for future patients
    • Most prescribers are unaware of the warning’s existence, with no strategy in place to inform them
    • No calls for smaller dosing for safer cessation
    • FDA seems unsure of how to safely taper and offers little guidance beyond “slow”
    • No awareness of the level of harm some patients are suffering
    • No warnings about withdrawal-induced akathisia or fluoroquinolone interactions

Why We Still Consider the FDA’s Boxed Warning a Victory for Patient Safety 

  • The FDA finally took a stance on benzodiazepines after more than 60 years of patient harm and regulator inaction.
  • The FDA officially recognized protracted withdrawal syndromes.
  • The FDA acknowledged the need to for slow tapering.
  • The FDA is an authority recognized by physicians, so patients and activists can cite their findings.
  • University’s Margolis Center for Health Policy held a public workshop, with FDA officials and other benzodiazepine-concerned professionals, to discuss possible solutions.
  • Our director spoke at Duke’s workshop about prescribed benzodiazepine harm:

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