Gabapentin: a pooled analysis of adverse events from three clinical trials in patients with postherpetic neuralgia.
BACKGROUND
Gabapentin has been shown to be well tolerated and effective in the management of the pain associated with postherpetic neuralgia (PHN). It is assumed that adverse events occurring with gabapentin are dose related, their frequency and severity increasing with increasing doses.


OBJECTIVE
The aim of this study was to assess the dose dependence of adverse events with gabapentin by determining the relationship between increasing doses of gabapentin and the onset and/or worsening of adverse events in patients with PHN.


METHODS
Data were pooled from 3 randomized, double-blind, placebo-controlled, parallel-group studies of gabapentin that focused on or included patients with PHN. Gabapentin was initiated at 300 mg/d and titrated to maintenance doses of 1800 to 3600 mg/d by day 12 to 24. The analysis of adverse events was based on 3 distinct groups: patients who received gabapentin <1800 mg/d, those who received gabapentin >or=1800 mg/d, and those who received placebo. Patients who were given higher doses of gabapentin had already received lower doses. An adverse event was recorded at the dose of its first onset and recorded again if its severity worsened at a higher dose.


RESULTS
This study included data from 603 patients with PHN: 358 patients (196 [54.7%] women, 162 [45.3%] men; mean [SD] age, 72.3 [10.3] years) received gabapentin, and 245 (133 [54.3%] women, 112 [45.7%] men; mean [SD] age, 73.3 [10.7] years) received placebo. The 3 most common adverse events were dizziness, somnolence, and peripheral edema. Patients receiving gabapentin >or=1800 mg/d had a higher incidence of peripheral edema (7.5%) than those receiving gabapentin <1800 mg/d (1.4%) or placebo (1.6%) (P<0.002, gabapentin >or=1800 mg/d vs placebo). In contrast, the incidence of dizziness and somnolence was not higher in patients receiving gabapentin >or=1800 mg/d compared with those in the other groups. Compared with placebo recipients, patients receiving gabapentin <1800 mg/d reported a significantly greater frequency of dizziness (20.2% gabapentin <1800 mg/d vs 7.4% placebo; P<0.002) and somnolence (14.9% vs 5.8%, respectively; P=0.005). However, at >or=1800 mg/d, rates of dizziness (9.7%) and somnolence (6.9%) were comparable to those with placebo. Discontinuation rates were comparable between patients receiving gabapentin and those receiving placebo.


CONCLUSIONS
In this pooled analysis of adverse-event data from 3 clinical trials in patients with PHN, the incidence of peripheral edema was increased when gabapentin was titrated to >or=1800 mg/d. Dizziness and somnolence, the other most commonly occurring adverse events, were transient and did not occur more frequently or worsen with titration to >or=1800 mg/d. Based on these findings, it does not appear that safety concerns should limit titration of gabapentin to achieve optimal efficacy.
Parsons
Bruce
B
Pfizer Inc., New York, NY 10017-5755, USA.
Tive
Leslie
L
Huang
Sue
S
D000368:Aged; D000588:Amines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004487:Edema / Q000139:chemically induced; D005260:Female; D000077206:Gabapentin; D006562:Herpes Zoster / Q000150:complications*; D006801:Humans; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin