Gabapentinoids & COPD Exacerbations

In 2019, the FDA warned that serious breathing difficulties may occur in patients using gabapentin or pregabalin who have respiratory risk factors, including the use of opioid medicines and other drugs that depress the central nervous system, and conditions such as COPD that reduce lung function.

In further support of this warning, a recent study published in the Annals of Internal Medicine found that patients with COPD who take gabapentinoids may be at higher risk for severe exacerbations. Researchers used health insurance data to perform a cohort study of patients with COPD who started taking gabapentinoids between 1994 and 2015 for epilepsy or pain, matching them 1:1 with nonusers on COPD duration, gabapentinoid indication, age, sex, calendar year, and time-conditional propensity score. The primary outcome was severe COPD exacerbation requiring hospitalization. Patients were followed until the primary outcome occurred or prescription drug coverage ended, until gabapentinoid treatment was discontinued or started (users vs nonusers), until death, or until the study ended in 2015.

356 patients with epilepsy, 9,411 with neuropathic pain, and 3,737 with other chronic pain who had COPD and were taking gabapentinoids were matched with nonusers with COPD. Mean age for those with each indication was ~73 years, ~76 years, and ~74 years, respectively. Use of gabapentinoids was associated with increased risk for severe COPD exacerbation in those with epilepsy (hazard ratio [HR], 1.58; 95% CI, 1.08-2.30), neuropathic pain (HR, 1.35; 95% CI, 1.24-1.48), other chronic pain (HR, 1.49; 95% CI, 1.27-1.73), and overall (HR, 1.39; 95% CI, 1.29-1.50). Exacerbation risk was similar with gabapentin and pregabalin.

Source: Rahman et al. Ann Intern Med. 2024

The authors noted that COPD was defined according to use of relevant medications, that information on smoking and race and ethnicity was lacking, and that their results could have been affected by residual confounding, among other limitations. “In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation,” they concluded. “These findings support the warnings from regulatory agencies and highlight the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD.”

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