Gabapentinoids linked to severe COPD exacerbation

Key takeaways

• The FDA issued a warning in 2019 about serious breathing problems associated with gabapentinoids.
• The study findings support warnings from the FDA and other regulatory agencies.

Gabapentinoid use was associated with severe exacerbation among users with COPD, supporting warnings from regulatory agencies about potentially serious adverse effects of the drugs, according to researchers.

In 2019, the FDA warned patients and providers about serious breathing problems associated with gabapentinoids, particularly among patients with respiratory risk factors such as COPD, Alvi A. Rahman, MSc, a PhD candidate in the department of epidemiology at McGill University in Canada, and colleagues wrote in Annals of Internal Medicine.

“Nevertheless, no population-based studies have been done among patients with COPD to investigate the potential respiratory adverse effects of gabapentinoids,” they wrote.

So, the researchers conducted a population-based cohort study to investigate the association. The analysis included health insurance data on 356 gabapentinoid users with epilepsy, 9,411 users with neuropathic pain and 3,737 users with other chronic pain, all of whom initiated use between 1994 and 2015. Gabapentinoid users were matched in a 1:1 ratio to nonusers on indications for gabapentinoid use, COPD duration, age, gender, calendar year and time-conditional propensity score.

Rahman and colleagues found that, compared with nonuse, gabapentinoids were linked to an increased risk for severe COPD exacerbation among those using the drug for:

• epilepsy (HR = 1.58; 95% CI, 1.08-2.3);
• neuropathic pain (HR = 1.35; 95% CI, 1.24-1.48); and
• other chronic pain (HR = 1.49; 95% CI, 1.27-1.73).

In the overall cohort, the HR for increased exacerbation risk associated with gabapentinoids was 1.39 (95% CI, 1.29-1.5) compared with nonuse.

“The peak increase in risk for severe COPD exacerbation occurred after approximately 6 months of continuous gabapentinoid use,” the researchers wrote.

They added that the risk occurred among users with neuropathic pain and other chronic pain regardless of age, sex, prior use of inhaled corticosteroids and the prior number of COPD exacerbations.

Although public health agencies have issued warnings of respiratory depression as a severe side effect of gabapentinoids, “these directives are yet to be echoed in clinical practice guidelines for the management of COPD and of neuropathic pain,” Rahman and colleagues wrote.

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

The study was limited by residual confounding, “including from lack of information on current or previous smoking,” the researchers noted.

“Given the likelihood of residual confounding, the risk for severe exacerbation associated with gabapentinoids may have been overestimated,” they added.

Still, Rahman and colleagues concluded that the 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.”