A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain

Abstract

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.

Keywords: adverse events; diabetic; neuralgia; pain; peripheral neuropathic pain; postherpetic neuralgia; pregabalin; safety.

Figure 1

Risk difference for common adverse events by age group. Risk difference with 95% confidence interval (CI) for patients < 65 years and ≥ 65 years for each AE (pregabalin, n = 4,883; placebo, n = 2,626). The risk difference for each AE, for all patients (of any age), is also shown. Those AEs with a risk difference for which the lower limit of the 95% CI was > 1% (for pregabalin all-doses) are shown.

Figure 2

Time to onset and resolution of common adverse events in studies of flexible-dose pregabalin. Kaplan–Meier plots of (A) time to onset and (B) time to resolution of common adverse events (those with a risk difference > 3) in the pregabalin flexible-dose group. Data followed similar trends for other doses of pregabalin and for placebo, for both time to onset and time to resolution.