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.
In September, 2020, the FDA announced a new boxed warning for benzodiazepines. This is the timeline of how that warning came to be.
Benzodiazepine Information Coalition’s Call-to-Action
- 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:
- physical dependence
- withdrawal reactions
- The FDA now recommends:
- judicious benzodiazepine prescribing
- gradual benzodiazepine tapering
- standardized warning labels on all benzodiazepines
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:
- Dr. Christy Huff’s blog on KevinMD The updated benzodiazepine boxed warning: What you need to know
- To view the full report from our Freedom of Information Act request about this warning click HERE.
- FDA Drug Safety Communication
- New FDA Study Shows Benzodiazepines Can Cause Long Term Injury