Opioids, benzodiazepines now require boxed warnings outlining risks of combined use

As part of the fight against opioid overdoses and deaths, the FDA now requires boxed warnings containing the risks associated with taking opioids and benzodiazepines simultaneously. In a data review, the FDA found that providers have been increasingly prescribing opioid analgesics and opioid-containing cough products along with benzodiazepines in recent years.


The updated warnings will apply to almost 400 different products, and will contain information about the risks of extreme sleepiness, respiratory depression, coma, and death when using the products together. FDA Commissioner Robert Califf stated that prescribers should carefully evaluate whether the benefits of using these medications together outweigh the serious risks on a patient-by-patient basis.

Opioid analgesics include oxycodone, hydrocodone, morphine, and other brand and generic medications designed to reduce pain. Benzodiazepines are used for treating neurological and psychological conditions, such as anxiety and seizure disorders. Although both classes of drugs depress the central nervous system (CNS), their differences require unique labeling information and slightly different warnings.


The FDA began reviewing scientific information about the combined use of these drugs even before it received a citizen petition in February 2016 requesting changes to existing labeling. The review revealed that the number of patients prescribed both drugs increased by 2.5 million between 2002 and 2014, or about 41 percent. Between 2004 and 2011, the rate of emergency department visits for non-medical use of both drug classes increased significantly, while overdose deaths nearly tripled. The new warning requirements are part of the agency’s Opioids Action Plan developed in response to the growing epidemic. The agency provided a response to the citizen petition and examples of labeling change notification letters.