Concomitant exposure to pregabalin in the preceding 120 days was associated with significantly increased odds of opioid-related death compared with exposure to opioids alone (adjusted odds 1.68; 95% CI, 1.19 to 2.36]). The researchers note that although current product monographs for gabapentin contain warnings about serious adverse events when this agent is combined with opioids, those for pregabalin do not. They call for a revision of the pregabalin product monographs based on these findings.
An editorial commends the researchers for completing a high-quality pharmacoepidemiologic study that strongly attempts to rule out any residual confounding factors. It adds that the authors' observations are consistent with those of other recently published studies, reinforcing the value of elucidating the potential interactions between these 2 drug classes to delineate best practices for their use. From a regulatory perspective, it notes that the US FDA is engaging in initiatives to determine what changes, if any, are needed to address the labelling concerns raised by this study.
In 2017, the MHRA issued a warning about gabapentin being associated with a rare risk of severe respiratory depression even without concomitant opioid medicines. It highlighted that patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants, and elderly people might be at higher risk of experiencing severe respiratory depression. It advised that when prescribing gabapentin in patients who require concomitant treatment with opioid medicines, patients should be carefully observed for signs of CNS depression, such as somnolence, sedation, and respiratory depression, and the dose of either gabapentin or the opioid should be reduced appropriately. No reference was made to issues issue with pregabalin at that time.
This warning is reflected in the SPC for gabapentin which alludes to spontaneous and literature case reports of respiratory depression and/or sedation associated with gabapentin and opioid use. No such warnings are present in the pregabalin SPC.