The U.S. Food and Drug Administration is warning that serious breathing difficulties may occur in patients using gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) who have respiratory risk factors.

These include the use of opioid pain medicines and other drugs that depress the central nervous system, and conditions such as chronic obstructive pulmonary disease (COPD) that reduce lung function. The elderly are also at higher risk.

Gabapentin and pregabalin are FDA-approved for a variety of conditions, including seizures, nerve pain, and restless legs syndrome. The FDA evaluation of respiratory depression with the gabapentinoids provides some evidence contrary to the widely held belief that gabapentinoids lack drug interactions and have wide therapeutic indices. Published studies demonstrate these drugs can behave in an additive way to potentiate central nervous system (CNS) and respiratory depression.

The FDA evaluation shows that the use of these medicines, often referred to as gabapentinoids, has been growing for prescribed medical use, as well as misuse and abuse.

Gabapentinoids are often being combined with CNS depressants, which increases the risk of respiratory depression. CNS depressants include opioids, anti-anxiety medicines, antidepressants, and antihistamines. There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone.

Health care professionals should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when co-prescribing gabapentinoids with an opioid or other central nervous system (CNS) depressant such as a benzodiazepine. Patients with underlying respiratory disease and elderly patients are also at increased risk and should be managed similarly.

Shifting treatment from one CNS depressant to another may pose similar risks. Be aware of the potential additive effects of all these CNS depressants and plan accordingly, by starting with low doses, titrating carefully, and informing patients of the potential for CNS and respiratory depression and their symptoms.

Incorporating one or more medications with non-drug therapies is the prevailing approach for optimizing analgesia. However, pairing an opioid with any CNS depressant – a gabapentinoid, benzodiazepine, sedating antidepressant, sedating antipsychotic, antihistamine, or other product – will increase the risk of respiratory depression.

The gabapentinoid prescribing information already includes guidance for health care professionals to caution patients about dizziness, somnolence, and the potential for impaired ability to operate a car or complex machinery.

The FDA will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs.