Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis Patients

Abstract

Background Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking.Methods From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0-100, >100-200, >200-300, and >300 mg) and pregabalin (>0-100 and >100 mg).Results In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%-41%) and fall (26%-30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively.Conclusions Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.

Keywords: United States Renal Data System; gabapentin; hemodialysis; pregabalin.

Graphical abstract

Figure 1.

Flow diagram demonstrating selection of study cohort. BMI, body mass index; VA, Veterans Affairs. ^aPatients were also excluded if the following occurred in January 2011: death, kidney transplantation, change in modality away from in-center hemodialysis (e.g., home hemodialysis or peritoneal dialysis), uncertain/recovered function, loss to follow-up, withdrawal from dialysis, or loss of Part D coverage, which precluded ascertainment of exposure status as of February 2011.