A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain.

Pregabalin is a commonly used therapy currently recommended as first-line treatment for a number of neuropathic pain (NeP) conditions. Since licensure, a number of clinical trials of pregabalin in different NeP conditions have been completed from which additional data on safety and tolerability can be drawn. In this analysis, patient-level data from 31 randomized clinical trials of pregabalin in peripheral NeP sponsored by Pfizer were pooled and assessed for incidence of adverse events (AEs). Incidence by age, disease condition, and race, together with risk differences and time to onset and resolution of AEs, was assessed. In total, 7,510 patients were included: 4,884 on pregabalin (representing 805 patient-years treatment) and 2,626 on placebo. Pregabalin vs. placebo risk analysis identified 9 AEs with a risk difference, for which the lower limit of the 95% confidence interval (CI) was > 1%: dizziness (risk difference [95% CI]: (17.0 [15.4 to 18.6]), somnolence (10.8 [9.5 to 12.1]), peripheral edema (5.4 [4.3 to 6.4]), weight increase (4.7 [3.9 to 5.5]), dry mouth (2.9 [2.1 to 3.8]), constipation (2.3 [1.5 to 3.2]), blurred vision (2.2 [1.6 to 2.9]), balance disorder (2.0 [1.5 to 2.5]), and euphoric mood (1.6 [1.2 to 2.0]). The most common AEs, dizziness and somnolence, typically emerged within the first 1 to 2 weeks of treatment and resolved 1 to 2 weeks later, without resulting in cessation of treatment. The data from this review provide information, indicating which AEs may be expected in patients treated with pregabalin, and suggest that careful dose titration to the highest tolerable dose is the most appropriate approach in clinical practice.

Efficacy and safety of pregabalin in patients with spinal cord injury: a pooled analysis.

OBJECTIVE: To summarize the efficacy and examine the safety and tolerability of pregabalin in patients with central neuropathic pain due to spinal cord injury (SCI). RESEARCH DESIGN AND METHODS: Data were pooled from two 12 to 16 week, placebo-controlled trials of pregabalin in patients with neuropathic pain due to SCI. Pain diaries were used to rate pain from 0 = no pain to 10 = worst possible pain. Efficacy measures included: mean change in pain from baseline to endpoint; duration adjusted average change (DAAC) in pain; the percentage of patients with ≥30% or ≥50% reductions in pain score from baseline to endpoint; and Patient Global Impression of Change (PGIC) score at endpoint. Adverse events (AEs) were also compared between treatment groups. RESULTS: In total 174 patients received placebo and 182 received pregabalin. Mean change in pain from baseline to endpoint was improved in the pregabalin group compared with placebo (placebo-adjusted difference = -0.79; 95% CI = -1.15, -0.43; p < 0.001; baseline-observation-carried-forward). DAAC in pain was improved in patients receiving pregabalin compared with placebo (p < 0.001). The percentage of patients achieving ≥30% and ≥50% reductions in pain from baseline to endpoint was greater in the pregabalin arm compared with placebo (placebo: 30% = 22.5%, 50% = 11.6: pregabalin 30% = 35.6%, 50% = 22.4%) (all p < 0.01). PGIC scores at endpoint were significantly better in the pregabalin arm compared with placebo (p < 0.05). Treatment-related AEs, most commonly somnolence, dizziness, dry mouth, fatigue, edema, blurred vision, and constipation occurred more frequently in patients treated with pregabalin than placebo. The majority of AEs were mild to moderate in severity. CONCLUSIONS: Pregabalin reduced neuropathic pain due to SCI over a 12 to 16 week treatment period. Treatment-related AEs were mostly mild to moderate in severity and are consistent with the known safety profile of pregabalin. These findings should not be extrapolated to longer durations of treatment or other patient populations.