FDA In Brief: FDA requires new warnings for gabapentinoids about risk of respiratory depression

December 19, 2019

Media Inquiries

The following quote is attributed to Douglas Throckmorton, M.D., deputy director for Regulatory Programs in the FDA’s Center for Drug Evaluation and Research:

“With the evolution of the opioid crisis, getting ahead of new concerns or addressing those that are already evident requires examining signs of misuse and abuse as soon as any signal emerges.

“Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co-use, including respiratory depression and increased risk of opioid overdose death.

“In response to these concerns, we are requiring updates to labeling of gabapentinoids to include new warnings of potential respiratory depressant effects. We are also requiring the drug manufacturers to conduct clinical trials to further evaluate the abuse potential of gabapentinoids, particularly in combination with opioids, with special attention being given to assessing the respiratory depressant effects.

“Our goal in issuing today’s new safety labeling change requirements is to ensure health care professionals and the public understand the risks associated with gabapentinoids when taken with central nervous system (CNS) depressants like opioids or by patients with underlying respiratory impairment. However, we do not want to unintentionally increase opioid use by turning prescribers away from this class of pain medications. ”

Related Information

The FDA is requiring new warnings about the risk of serious breathing difficulties that can lead to death in patients who use gabapentanoids with opioid pain medicines or other drugs that depress the central nervous system (CNS), or those who have underlying respiratory impairment, such as patients with chronic obstructive pulmonary disease (COPD) or the elderly. These warnings are based on a review of several sources of data including case reports submitted to the FDA or published in the medical literature, observational studies, human trials and animal studies.
Gabapentinoid products include gabapentin, which is marketed under the name Neurontin and Gralise, as well as generics; gabapentin enacarbil, a prodrug of gabapentin which is marketed as Horizant; and pregabalin, which is marketed as Lyrica and Lyrica CR, as well as generics. These drugs are prescribed to treat a variety of conditions, and some research and literature also suggest that clinicians may be prescribing gabapentinoids for unapproved or “off label” uses to patients with other types of pain, as alternatives to opioids.
An evaluation of drug utilization data shows increased prescription use of gabapentinoids. Between 2012 and 2016, the estimated number of patients who filled a gabapentin prescription increased from 8.3 million to 13.1 million annually, and the number of patients who filled a pregabalin prescription increased from 1.9 million to 2.1 million annually. In addition, data collected in 2016 from an office-based physician survey showed that an estimated 14% and 19% percent of patient encounters involving gabapentin and pregabalin, respectively, also involved opioids.
Health care professionals and patients should report side effects from gabapentin, pregabalin or other medicines to the FDA’s MedWatch program.

Additional Resources

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.