Do gabapentinoids increase the risk of severe exacerbations of COPD?

Health agencies in Canada and the United States have previously warned of severe breathing problems associated with gabapentinoids (gabapentin, pregabalin).1,2 The concern arises when these agents are used with other central nervous system depressants (e.g., opioids, antianxiety agents, antidepressants) or by patients with lung problems (e.g., chronic obstructive pulmonary disease [COPD]), although supporting evidence is limited. This is an important issue, as use of these agents has increased significantly, partly due to off-label prescribing.3To further examine the safety of gabapentinoids, researchers in Quebec assessed whether gabapentinoid use is associated with severe exacerbations in patients with COPD. The time-conditional propensity score-matched, new-user cohort study used information from health insurance databases from the Régie de l’assurance maladie du Québec.4Patients with COPD between 1994 and 2015 who were starting gabapentinoid therapy for epilepsy, neuropathic pain or another chronic pain condition were matched 1:1 with nonusers in terms of COPD duration, indication for gabapentinoids, age, sex, calendar year and time-conditional propensity score. The primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in the overall cohort and in subcohorts according to gabapentinoid indication.4Results showed the following:The cohort included 356 gabapentinoid users with epilepsy, 9,411 with neuropathic pain and 3,737 with another chronic pain condition, matched 1:1 with nonusers. Compared with nonuse, gabapentinoid use was associated with an increased risk for severe COPD exacerbation overall (HR 1.39 [95%CI 1.29–1.50]).Compared with nonuse, gabapentinoid use was associated with an increased risk for severe COPD exacerbation across the indications of epilepsy (HR 1.58 [95%CI 1.08–2.30]), neuropathic pain (HR 1.35 [95%CI 1.24–1.48]) and other chronic pain condition (HR 1.49 [95%CI 1.27–1.73]).4 The investigators conclude that in this study, gabapentinoid use was associated with increased risk for severe exacerbation in patients with COPD. These results support the warnings from regulatory agencies regarding risks of gabapentinoids in patients with pulmonary disease. The study results also highlight the importance of considering this potential risk before prescribing gabapentin or pregabalin to patients with COPD.4References1. Health Canada. Summary safety review—gabapentin—assessing the potential risk of serious breathing problems. September 16, 2016. (accessed January 18, 2024).2. US Food and Drug Administration. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) when used with CNS depressants or in patients with lung problems. December 19, 2019. (accessed January 18, 2024).3. Chan AYL, Yuen ASC, Tsai DHT, et al. Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study. Nat Commun 2023;14:5005. (accessed January 18, 2024).4. Rahman AA, Dell’Aniello S, Moodie EEM, et al. Gabapentinoids and risk for severe exacerbation in chronic obstructive pulmonary disease. A population-based cohort study. Ann Intern Med 2024; published online January 16, 2024. (accessed January 18, 2024).

Do gabapentinoids increase the risk of severe exacerbations of COPD?

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