FDA is warning that serious, life-threatening, and fatal respiratory depression has been reported with the gabapentinoids, gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). Most cases occurred in association with co-administered central nervous system (CNS) depressants, especially opioids, in the setting of underlying respiratory impairment, or in the elderly.
Our 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.
When co-prescribing gabapentinoids with another CNS depressant, particularly an opioid, or in patients with underlying respiratory impairment, initiate the gabapentinoid at the lowest dose.
Adjust the dose of both gabapentin and pregabalin in patients with renal impairment and patients undergoing hemodialysis, because both drugs are excreted by the kidneys.
Monitor for symptoms of respiratory depression and sedation, especially when co-prescribing gabapentinoids with an opioid or other CNS depressant such as a benzodiazepine or when prescribing to patients with underlying respiratory impairment, or elderly patients.
The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants, including the gabapentinoid. Gabapentinoids used for analgesia or seizure control should be tapered prior to discontinuation. See the prescribing information for specific tapering guidance.
Encourage patients to read the Medication Guide they receive with each gabapentinoid prescription, which explains the safety risks and provides other important information.
To help FDA track safety issues with medicines, report adverse events involving gabapentin, pregabalin, or other medicines to the FDA MedWatch program, using the information in the “Contact Us” box at the bottom of this page.