Gabapentin toxicity in patients with chronic kidney disease: a preventable cause of morbidity

Background: Gabapentin is frequently used as an analgesic in patients with chronic kidney disease. Although gabapentin is well known for its favorable pharmacokinetics, it is exclusively eliminated renally, and patients with chronic kidney disease are at risk for toxicity. Existing literature on such risk is lacking.

Methods: We examined the Mayo Clinic Rochester database from 1998 to 2007 in patients with serum gabapentin measurements and known medical outcomes. A total of 729 patients were stratified according to their estimated glomerular filtration rate: group I, 126 individuals with estimated glomerular filtration greater than 90 mL/min/1.72 mm(2) [corrected] ; group II, 594 individuals with estimated glomerular filtration less than 90 mL/min/1.72 mm(2) [corrected] without dialysis; group III, 9 individuals with chronic dialysis.

Results: Patients in groups II and III had higher serum gabapentin levels (8.39+/-0.32 microL/mL and 58.8+/-10.22 microL/mL, respectively) than in group I (5.52+/-0.32 microL/mL, P<.01). Toxicity occurred exclusively in groups II (5.56%) and III (77.8%); toxic manifestations were more severe in group III than in group II. Elderly individuals with multiple comorbidities were overrepresented in those with toxic manifestations. Gabapentin toxicity was suspected initially in only 41.5% of symptomatic cases.

Conclusion: Gabapentin toxicity in patients with chronic kidney disease is underrecognized. Patients with chronic kidney disease often receive inappropriately high gabapentin dosage for their kidney function, occasioning overt toxicity; advanced age and comorbidity predispose these patients for toxicity. Heightened awareness of such preventable risk, amid the chronic kidney disease epidemic, would be cost-effective and improve healthcare quality.