Should Gabapentin Be Dose Adjusted: What are the Clinical Consequences?

Objective: To review the clinical necessity of renal dose adjustment of gabapentin. Data Sources: Medical literature (1966–February 2006, week 2) was accessed through MEDLINE, EMBASE, Pre-MEDLINE, International Pharmaceutical Abstracts, and the manufacturer's package insert. Search terms included gabapentin, side effects/adverse effects, overdose, toxicity, and renal impairment. Literature references were consulted for relevant information. Study Selection and Data Extraction: All studies from the data sources that were published in English were evaluated. Case reports, case series, and clinical trials with primarily adult populations were included in the review to determine the clinical necessity of dosage adjustment, including morbidity and mortality associated with dose adjustment failure. Case reports of gabapentin overdose were evaluated for clinically significant outcomes. All reports were examined for clinical relevance and adequate information to address the issue of major clinical consequences of failure to dose adjust gabapentin in specific patient populations, including renally impaired and elderly patients. Data Synthesis: The package insert suggests dose adjustment of gabapentin in patients with decreased renal function, yet published information regarding clinical consequences of gabapentin in patients is limited. Although gabapentin possesses a favorable safety profile and is generally well tolerated, there have been cases reporting serious adverse effects. While clinical studies and the majority of case reports demonstrate minimal adverse effects, there is some concern that select patients may experience serious outcomes if the drug is not dose adjusted. Conclusions: The recommendation for dosage adjustment is suitably based upon the pharmacokinetic properties of gabapentin, yet healthcare practitioners should determine the need for gabapentin dosage adjustment in specific patients. There should be continued emphasis on recommending renal dose adjustments, with the most concern applied to the elderly and patients with significant renal impairment/end-stage renal disease.