Gabapentinoids increase risk of exacerbations in COPD

Chronic obstructive pulmonary disease (COPD) patients treated with gabapentinoids faced a nearly 50% higher risk of severe exacerbations. Also, respiratory failure was markedly elevated while on this medication.

Gabapentinoids, i.e. gabapentin and pregabalin, are anticonvulsants that also indicated for neuropathic pain [1]. “However, in the last decade, the use of these drugs has risen dramatically in both America and Europe, with rates of prescription tripling, and this is thought to be partly due to off-label prescribing for any type of pain,” Mr Alvi Rahman (McGill University, Canada) explained [2]. Several health authorities have issued warnings of possible respiratory problems when using gabapentinoids, also in patients with COPD. Mr Rahman elaborated that these warnings are mostly based on case reports and that data from large studies supporting this evidence is still lacking.

To assess the possibility of a link between gabapentinoid use and hospitalisation as equivalent for severe exacerbation in patients with COPD, data was used from the Régie de l’assurance maladie du Quebec (RAMQ), a provincial health insurance program. Out of 156,803 COPD patients, 23,061 individuals starting on gabapentinoids were matched 1:1 with non-users by propensity score. Mean age within the cohort was 74.6 years and 56.5% were women. During the included 72,349 person-years (PY) of follow-up, a total of 6,232 severe COPD exacerbations happened with an incident rate of 14.1/100 PY versus 7.6/100 PY in gabapentinoid-users versus non-users. This corresponded to an adjusted hazard ratio (aHR) of 1.47. Concerning moderate to severe exacerbations and respiratory failure also demonstrated higher risks for those on gabapentinoids (aHR 1.15 (95% CI 1.10-1.19) and aHR 1.47  (95%CI 1.38-1.57)  , respectively). “We also looked at different patient subgroups to assess whether the risk varied according to the subgroups and overall, the risk was consistent,” Mr Rahman explained, concerning stratifications for age, sex, previous COPD exacerbations, and different groups of prior medications. Conducted sensitivity analyses confirmed and supported the main findings.
In his conclusion, Mr Rahman underlined that this was the first population-based study to demonstrate an association between gabapentinoid use and severe COPD exacerbation. “It supports previous warnings from the health agencies and it emphasises close monitoring and a risk-benefit assessment when prescribing gabapentinoids in this population,” Mr. Rahman indicated. He further encouraged good coordination of care between general practitioners and specialists about prescribing these drugs.

1. Mathieson S, et al. BMJ. 2020;369:m1315.
2. Rahman A. Gabapentinoids and the risk of severe exacerbations in patients with chronic obstructive pulmonary disease. Abstract 884, ERS International Congress 2023, 9–13 September, Milan, Italy.

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Posted on 29 October 202329 October 2023