With benzodiazepine prescribing increasing for approved indications and off-label uses, the FDA is taking action to make the use of the drug class safer for patients. The agency announced in a Drug Safety Communication that it is requiring an update to the boxed warning for benzodiazepines to now include the risks for abuse, misuse, addiction, physical dependence, and withdrawal reactions.
The FDA is also requiring class-wide changes to the Warnings and Precautions, Drug Abuse and Dependence, and Patient Counseling Information sections of the prescribing information for all benzodiazepine products. In parallel, revisions will be made to the existing patient Medication Guides to help educate patients and caregivers about these risks.2
In 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient pharmacies, according to the FDA, but those numbers have been on the rise for more than a decade. An analysis of 386,457 outpatient visits found benzodiazepine prescriptions jumped from 3.8% of prescriptions in 2003 to 7.4% in 2015. While prescribing is most common for anxiety and depression (34% in 2015), chronic pain prescriptions increased during that period from 3.6% to 8.5% (JAMA Netw Open 2019;2:e187399).
What makes that increase so concerning is that more than 30% of opioid-related deaths also involve benzodiazepines (JAMA 2013;309:657-659). A study using urine drug testing found that nearly one in five specimens (19%) that were positive for prescribed opioids also contained nonprescribed benzodiazepines. Furthermore, over 15% of specimens with prescribed benzodiazepines also showed nonprescribed opioids (J Addict Med 2017;11420-426).
The FDA stressed that physical dependence can occur even when benzodiazepines are taken for several days. Patients who take a benzodiazepine for weeks or months can experience withdrawal signs and symptoms when the medicine is discontinued abruptly or continued at lower doses. Stopping benzodiazepines abruptly or reducing the dosage too quickly can result in acute withdrawal reactions, including potentially fatal seizures. In 2018, an estimated 50% of patients who were given oral benzodiazepines received them for two months or longer, according to the FDA.
“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol, and illicit drugs,” said FDA Commissioner Stephen M. Hahn, MD, in a press release. “We are taking measures and requiring new labeling information to help health care professionals and patients better understand that while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction, and dependence.”