medwireNews: Gabapentinoid use by patients with chronic obstructive pulmonary disease for epilepsy, neuropathic pain, or other chronic pain is associated with an increased risk for severe exacerbations, suggests a population-based cohort study.
“This study supports the warnings from regulatory agencies and highlights the importance of considering the potential risk when prescribing gabapentin and pregabalin to patients with COPD,” say Christel Renoux (Jewish General Hospital, Montreal, Quebec, Canada) and colleagues.
They collated information from three healthcare databases to create a cohort of 156,803 patients (aged ≥55 years) with COPD, based on the receipt of three or more prescriptions for a respiratory drug, such as long-acting β-agonists (LABA), muscarinic antagonists, a combination of the two, or LABA-inhaled corticosteroids, on at least two different occasions in the year 1994–2015.
From this cohort, 13,504 individuals who started taking gabapentinoids for epilepsy (n=356), neuropathic pain (n=9411), or other chronic pain (n=3737) were time-conditional propensity score-matched to an equal number of COPD patients with the same indication who did not use gabapentinoids but had the same duration of COPD and were of the same age and sex.
Over a mean follow-up of 1.5 years and a gabapentinoid treatment duration of 6 months, the risk for a severe COPD exacerbation, defined as a first hospitalization for COPD or death due to a COPD exacerbation, was increased by a significant 58% among COPD patients using gabapentinoids for epilepsy compared with those not using them.
Similarly, the risk was increased by a significant 35% and 49% for COPD patients taking gabapentinoids for neuropathic pain or other chronic pain, respectively, over a mean 1.6-year follow-up and a mean 5-month treatment duration.
The incidence rates for severe exacerbation with gabapentinoid use compared with nonuse among COPD patients taking it for epilepsy were 22.4 and 10.7 per 100 person–years, respectively, and for those taking gabapentinoids for neuropathic and other chronic pain, a corresponding 15.3 versus 8.7 per 100 person–years and 14.0 versus 7.3 per 100 person–years. For the cohort overall, the respective rates were 15.1 versus 8.3 per 100 person–years and the increased risk was a significant 39%.
The researchers note in the Annals of Internal Medicine that differences in incidence between gabapentinoid use and nonuse occurred soon after treatment initiation and the increased risk for severe exacerbation peaked at about 6 months of continuous use.
Also, the increased risk with gabapentinoid use was seen “regardless of age, sex, and various markers of COPD severity,” they report.
The findings were consistent in several sensitivity analyses assessing, for instance, the effects of increasing the grace period between successive prescriptions from 7 days to 15 and 30 days, limiting the follow-up period to 1 year, and excluding patients with possible use of cancer-related palliative pain medication.
Renoux and team caution that there is potential for residual confounding in their study, because current or previous smoking status was not considered and “patients prescribed gabapentinoids may more likely be active smokers and at greater risk for COPD exacerbation.”
They stress that “[p]ublic health agencies have released warnings of respiratory depression as a potentially serious adverse effect of gabapentinoids, including for patients with COPD,” but note that “these directives are yet to be echoed in clinical practice for the management of COPD and of neuropathic pain.”
Therefore, “our findings may help inform the prescription of gabapentinoids in patients with COPD,” the authors conclude.
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