Tolerability and safety of gastroretentive once-daily gabapentin tablets for the treatment of postherpetic neuralgia

Abstract

ObjectiveAn immediate-release formulation of gabapentin is approved for treatment of postherpetic neuralgia (PHN). This formulation, however, requires multiple daily dosing, usually three times per day, and is associated with a high incidence of somnolence and dizziness. We assessed the tolerability and safety of a once-daily gastroretentive formulation of gabapentin (G-GR) in phase 3 clinical trials in patients with PHN.Research design and methodsData were pooled from two placebo-controlled studies involving 723 patients (G-GR 1800 mg, n = 359; placebo, n = 364). Patients (43% male, mean age 66 years) with PHN pain >4 (0–10 scale) for ≥3 months were enrolled. Summary statistics for the incidence of treatment-emergent adverse events (AEs) were performed. Laboratory parameters and vital signs were assessed.ResultsTreatment-emergent AEs were reported in 48% of patients (G-GR, 54%; placebo, 42%) and led to discontinuation in 8% of patients (G-GR, 10%; placebo, 7%). The most frequent (≥3% in any group) AEs were dizziness (G-GR, 11%; placebo, 2%), somnolence (G-GR, 5%; placebo, 3%), headache (G-GR, 4%; placebo, 4%), peripheral edema (G-GR, 4%; placebo, <1%), and diarrhea (G-GR, 3%; placebo, 3%). Serious AEs were reported in seven patients in the G-GR group (2%) and ten patients in the placebo group (3%). There were two deaths, both in the placebo group. No serious AEs were considered related to treatment. Mean values for laboratory parameters and vital signs at the end of each study were similar between groups.ConclusionG-GR was safe and well tolerated for the treatment of PHN.

Real-world Experience With Once-daily Gabapentin for the Treatment of Postherpetic Neuralgia (PHN)

“…The overall percent of patients experiencing any AE was very similar between this study and the previous phase 3 studies (51% vs. 54%), as were the profiles of the most common AEs, dizziness and somnolence. 11 , 12 In this study, dizziness was reported for 13.7% of patients compared with 10.9% in the 2 phase 3 studies. Somnolence was reported for 5.6% compared with 4.5% in the phase 3 studies.…”

“…The overall percentage of patients 70 years and below and above 70 years experiencing an AE in the current study (51% for each group) was similar to the rates observed in the phase 3 studies (58% for patients below 65 y and 52% for patients 65 y and above). Although, older patients (above 70 y) in this study experienced slightly more dizziness, somnolence, nausea, and diarrhea, and were more likely to discontinue because of AEs than in the phase 3 studies, 12 this was likely due to differences in the study design. In its quest to best approximate real-world usage, this study permitted entry of patients previously unable to tolerate gabapentin or pregabalin and the use of concomitant medications was permitted.…”

“…Somnolence was reported for 5.6% compared with 4.5% in the phase 3 studies. 11 , 12 These AE rates were considerably lower than those reported with immediate-release gabapentin, where dizziness was reported in 24% to 33% of patients and somnolence in 17% to 27%. 2 , 3 This is especially notable because unlike previous studies of gabapentin in PHN, 2 , 3 , 9 , 10 , 16 patients with known intolerance to gabapentin or pregabalin were not excluded.…”

“…The most common adverse events (AEs) observed for G-GR-treated patients were dizziness (10.9%), somnolence (4.5%), and headache (4.2%). 11 , 12 These rates of dizziness and somnolence were lower than what was observed in similar clinical studies with immediate-release gabapentin (dizziness, 28.0%; somnolence, 21.4%). 13 In the G-GR clinical studies, 6.9% of patients in the placebo arm and 9.7% of patients in the G-GR arm discontinued study treatment due to AEs, most commonly because of dizziness.…”

Practical considerations in the pharmacological treatment of postherpetic neuralgia for the primary care provider

“…To improve the efficacy, safety, and tolerability of PHN therapy through simplified dosing regimens and shorten titration periods, two extended-release formulations of gabapentin were developed and recently approved by the FDA for the treatment of PHN: gastroretentive gabapentin (Gralise®; Depomed, Newark, CA, USA), approved in 2011,55 and gabapentin enacarbil (Horizant®; XenoPort, Santa Clara, CA, USA), approved in 201256 (Table 1). The dosing regimen for gastroretentive gabapentin is reduced to once daily, and a majority of patients (over 90%) reach therapeutic dosage within 2 weeks 57. Gabapentin enacarbil is dosed twice daily with a 4-day to 1-week titration period 58.…”