Gabapentinoid Use Linked to Risk for Severe COPD Exacerbations

Patients with chronic obstructive pulmonary disease (COPD) who use gabapentinoids for epilepsy, neuropathic pain, and other chronic pain have an increased risk for severe COPD exacerbations, researchers reported in the Annals of Internal Medicine.

Gabapentinoids (eg, gabapentin and pregabalin) are indicated for treatment of epilepsy and neuropathic pain. Although warnings have been issued about the risk for severe breathing problems associated with gabapentinoids, evidence supporting this issue is limited. Researchers therefore conducted a population-based cohort study to assess severe exacerbations among patients with COPD who had an approved or off-label indication for gabapentinoids (eg, epilepsy, neuropathic pain, or other chronic pain). The study employed use of a time-conditional propensity score (TCPS)-matched, new-user design.

Data were obtained from 3 computerized health care databases in Quebec, Canada. A base cohort was established among patients aged 55 years or older who received at least 3 prescriptions for a respiratory drug (long-acting β-agonist [LABA], long-acting muscarinic antagonist [LAMA], or a combination of LABA-LAMA or LABA-inhaled corticosteroid [ICS]) for at least 2 different dates within a 1-year period from January 1, 1994, to December 31, 2015. All patients initiating treatment with a gabapentinoid who also had a potential indication (ie, epilepsy, neuropathic pain, or other chronic pain) were then identified.

Each participant initiating gabapentinoid treatment was matched, based on TCPS, 1:1 without replacement to the control group participant with the closest TCPS. The primary outcome was severe COPD exacerbation, defined as an initial COPD hospitalization during follow-up or death from a COPD exacerbation.

The analysis included 356 individuals who had initiated gabapentinoid treatment who had epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain; these individuals were matched with an equal number of individuals who did not use gabapentinoids. The mean follow-up for patients with an epilepsy indication was 1.5 years, with a mean gabapentinoid treatment duration of 0.6 years. The mean follow-up was 1.6 years and the mean treatment duration was 0.5 years for patients with the 2 other indications.

Gabapentinoid use was associated with a higher risk for severe COPD exacerbations vs nonuse for the 3 indications. The peak increase for severe COPD exacerbation risk was observed after about 6 months of continuous gabapentinoid use.

Gabapentinoid use vs nonuse was associated with an increased risk for severe COPD exacerbations among individuals with epilepsy (adjusted hazard ratio [aHR], 1.58; 95% CI, 1.08-2.30), neuropathic pain (aHR, 1.35; 95% CI, 1.24-1.48), other chronic pain (aHR, 1.49; 95% CI, 1.27-1.73), and overall (aHR, 1.39; 95% CI, 1.29-1.50).

Estimates in patients with epilepsy had high uncertainty in stratified analyses. For patients with neuropathic pain and other chronic pain, the risk was found regardless of age, sex, number of previous COPD exacerbations, prior use of ICS, number of respiratory medications used, or opioid or benzodiazepine use at enrollment.

Findings in the sensitivity analyses and post hoc analyses were consistent with results in the primary analysis.

Study limitations include potential misclassification of patients with asthma among those who were prescribed LABA-ICS. In addition, the data may be more likely to include patients with COPD aged 65 years and older, and residual confounding is possible.

“In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation,” the study authors 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,” stated the investigators.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Pulmonology Advisor