Gabapentinoids in COPD Patients May Raise Risk for Severe Exacerbations

Gabapentinoid use in patients with chronic obstructive pulmonary disease (COPD) was associated with a higher risk for severe exacerbations, a population-based cohort study from Canada indicated.

Among more than 27,000 COPD patients, those who started therapy with the anticonvulsant for either epilepsy, neuropathic pain, or some other form of chronic pain had a 39% greater risk for severe exacerbations compared with a matched group of nonusers (HR 1.39, 95% CI 1.29-1.50), reported Christel Renoux, MD, PhD, of the Lady Davis Institute and Jewish General Hospital in Montreal, and colleagues in Annals of Internal Medicine.

The findings were consistent across age, sex, and COPD severity, and the increased risk for severe exacerbations remained consistent across the three subgroups studied:

• Epilepsy: 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)

“Public health agencies have released warnings of respiratory depression as a potentially serious adverse effect of gabapentinoids, including for patients with COPD,” wrote Renoux and co-authors. “However, these directives are yet to be echoed in clinical practice guidelines for the management of COPD and of neuropathic pain.”

“Several guidelines for the management of neuropathic pain recommend gabapentinoids as first-line pharmacotherapeutic options,” they continued. “Although one guideline noted gabapentinoids’ potential for misuse and dependence, none mentioned the potential for respiratory adverse effects. Thus, our findings may help inform the prescription of gabapentinoids in patients with COPD.”

On- and off-label gabapentinoid prescriptions are on the rise across North America, partly in response to the opioid epidemic, the authors suggested, given that the class of drugs are often perceived as a safer alternative to opioids.

“These trends are of concern because gabapentinoids are not effective in many of these off-label indications, yet they expose patients to potentially serious adverse effects,” Renoux and co-authors noted. “In particular, their propensity to cause central nervous system depression leading to sedation and respiratory depression has been reported in both animal and human studies.”

The analysis used three digital health insurance databases in Quebec and included 13,504 COPD patients ages 55 and older exposed to gabapentinoid from 1994 to 2015 for either epilepsy (n=356), neuropathic pain (n=9,411), or other chronic pain (n=3,737). These patients were matched to an equal number of COPD patients with epilepsy, neuropathic pain, or other chronic pain but who were not exposed to gabapentinoids.

The study’s main outcome was a severe COPD exacerbation requiring hospital admission or resulting in death.

For secondary outcomes, gabapentinoid use was also associated with an increased risk for either moderate or severe exacerbations, as well as respiratory failure, in patients taking the drugs for neuropathic or other chronic pain. Precision was limited regarding this association in patients with epilepsy, the researchers reported.

COPD was defined by relevant medications for the condition based on ICD codes, which included the possibility of misclassification if patients were prescribed long-acting beta-agonist/inhaled corticosteroids for asthma.

Other limitations included that data on race/ethnicity were missing, as were details on smoking status, and that the study may have captured more patients ages 65 and older, “because all persons in this age group are insured for prescription medication in Quebec,” Renoux and colleagues said.

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