Two well-studied conditions of peripheral
neuropathic pain are
postherpetic neuralgia (PHN) and painful diabetic
peripheral neuropathy (
DPN). Several
pregabalin trials for peripheral
neuropathic pain have been conducted in the West, but limited data are available for Japan. As ethnicity may influence health risks, differences may be evident in safety data from
pregabalin trials in Japan and in the West. The objectives of this review were to compare large pooled safety data from randomized controlled trials evaluating
pregabalin for the treatment of PHN or
DPN in the West with data from two (one PHN, N = 371; one
DPN, N = 314) similar trials in Japan. Longer-term safety data from Japanese open-label extension studies were also reviewed in these
neuropathic pain populations. Published and unpublished Pfizer-supported
pregabalin trials were identified and sourced from internal Pfizer records. A PubMed search to check for inclusiveness was conducted on 2 November 2011 using the following criteria: 'diabetic
peripheral neuropathy' OR '
postherpetic neuralgia' OR '
neuropathic pain' AND '
pregabalin', with limits set for clinical and randomized controlled trials published in English. Five PHN trials (N = 1250) and nine
DPN trials (N = 2554) were identified as suitable for inclusion based on methodological comparability. Descriptive safety data from the original trials were reviewed and the most commonly reported adverse events (AEs;
dizziness,
somnolence, peripheral oedema and
weight gain) were identified to be of primary interest. The majority of AEs were of mild to moderate severity in Japanese and Western populations. The most commonly reported AE data (all-causality) with
pregabalin (regardless of dose) in Japan (
dizziness: PHN = 31.1%; DPN = 24.6%, and
somnolence: PHN = 28.6%; DPN = 25.7%) were compared with pooled data from the Western trials (
dizziness: PHN = 24.9%; DPN = 23.0%, and
somnolence: PHN = 15.1%; DPN = 13.4%). Further assessment of these pooled AE (all-causality) data showed that
dizziness and
somnolence appeared early in the course of
pregabalin treatment, but resolved before the end of the treatment in the majority of PHN and
DPN patients (maximum duration of trials was 13 weeks). The slightly higher incidence of
dizziness and
somnolence in the two Japanese trials than that seen in the Western trials may reflect an increased exposure to
pregabalin per fixed dose due to the lower mean bodyweight of the Japanese versus Western populations (on a mg/kg basis). However, of the participants who experienced these AEs (all-causality), the proportion who withdrew from the trials in Japan (
dizziness: PHN = 23.5%; DPN = 18.2%, and
somnolence: PHN = 10.3%; DPN = 10.9%) were comparable with the proportion who withdrew from trials in the West (
dizziness: PHN = 16.0%; DPN = 29.3%, and
somnolence: PHN = 19.4%; DPN = 34.2%). In Japan, 12.5% (PHN) and 15.1% (
DPN) of patients experienced peripheral oedema as an AE (all-causality) compared with 8.8% (PHN) and 10.3% (
DPN) in the West.
Weight gain as an AE (all-causality) was experienced in 11.7% (PHN) and 13.4% (
DPN) of patients in Japan compared with 3.8% (PHN) and 7.0% (
DPN) in the West, but stabilized with continued treatment. Despite the lower mean bodyweight in Japanese versus Western patients, the PHN and
DPN patients in Japan had stable
blood glucose and HbA(1c) levels throughout the trials. The results of this review indicate safety outcomes in
pregabalin trials are comparable between patients in Japan and those in the West. While managing peripheral
neuropathic pain with
pregabalin treatment, all patients should be observed closely for the incidence of
dizziness and
somnolence, especially at the beginning of treatment. These patients should also be monitored for evidence of peripheral oedema and
weight gain during stable treatment, regardless of the source of
neuropathic pain.