Long-term Safety of Gastroretentive Gabapentin in Postherpetic Neuralgia Patients

Jensen, Mark P.; Irving, Gordon; Rauck, Richard; Wallace, Mark; Sweeney, Michael F.; Vanhove, Geertrui F.

doi:10.1097/ajp.0b013e31827b32ab

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…In addition, oral dosage forms that adopt a different conformation in the gastric cavity to prolong gastric residence time have been described over the last 30 years. These attempts have been limited, however, by lack of safety mechanisms incorporated into the dosage forms that ensure ultimate safe passage through the GI tract (5–7) or limited (hours) duration of the gastric residence (8), or both. Recently, we developed new materials that can potentially improve safety and have the ability to fit into ingestible forms (9).…”

Section: Introductionmentioning

confidence: 99%

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

et al. 2016

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Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

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Section: Introductionmentioning

confidence: 99%

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

et al. 2016

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“…Furthermore, the evaluation of long-term safety and tolerability of G-GR revealed that, after reduction in AE incidence after 2-week titration period, the frequency, intensity, and severity of AEs did not change with long-term treatment. 43 Although patients who had not previously responded to gabapentin at daily doses >1200 mg were excluded from the phase 3 studies, exclusion criteria in the phase 4 study were limited to only those in the product label; thus the integrated patient population was not enriched with patients likely to be tolerant of gabapentin.…”

Section: Discussionmentioning

confidence: 99%

Relationships Among Adverse Events, Disease Characteristics, and Demographics in Treatment of Postherpetic Neuralgia With Gastroretentive Gabapentin

Shaparin

Slattum

Bucior

et al. 2015

The Clinical Journal of Pain

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Objectives:To characterize risk factors for occurrence of adverse events (AEs) and treatment discontinuations due to AEs for improving safety and tolerability of treatment of postherpetic neuralgia (PHN).Methods:Patients with PHN (n=556) received 1800 mg once-daily gastroretentive gabapentin (G-GR) in 2 phase 3 and 1 phase 4 study. Safety assessments included the incidence and severity of AEs and analysis of discontinuations due to AEs. Multivariable, logistic regression analyses examined predictors of AE reporting and discontinuations due to AEs.Results:In total, 53.2% of patients reported any AE, and 12.9% discontinued because of AEs. Both AE incidence and treatment discontinuations decreased rapidly during the 2-week titration to sustained, low levels. The probability to report any AE was 0.6 for females versus 0.4 for males, whereas there were no differences in probabilities for age (less than 75 vs. 75 y and older) and race (nonwhite vs. white). Consistent with this, only female sex was a significant (P=0.0006) predictor of AE reporting. Experiencing moderate (P≤0.0001) or severe (P=0.0006) AEs, but not patient demographics, was predictive of treatment discontinuations. The probability of discontinuation due to moderate AEs was 0.4 and 0.5 for severe AEs.Discussion:The tolerability of G-GR was not affected by patient age, but was affected by AE severity. Although being female was predictive of reporting AEs, it did not influence treatment discontinuation. Given that PHN is a disease for which the risk and duration of PHN increases with age and with being female, G-GR appears to be a well-suited treatment option for PHN.

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“…Furthermore, another adverse effect reported being associated with gabapentin was weight gain . However, long‐term treatment (up to 24 weeks) with gabapentin of 1800 mg was only associated with little weight gain (<1 kg) in patients with PHN …”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of gabapentin 1800 mg treatment for post-herpetic neuralgia: a meta-analysis of randomized controlled trials

Fan

et al. 2014

J Clin Pharm Ther

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SUMMARYWhat is known and objective: Gabapentin has been used for the management of post-herpetic neuralgia (PHN). However, inconsistent results have been reported. This meta-analysis was performed to assess the efficacy and safety of gabapentin 1800 mg/day in PHN patients by conducting a meta-analysis. Methods: Electronic databases were searched for relevant randomized controlled trials (RCTs) that compared gabapentin 1800 mg/day to placebo for PHN. The primary outcomes were reduction in 24-h average pain intensity scores, 50% and 30% pain intensity reduction and gabapentin-related side effects. The secondary outcomes were reduction in sleep rating scores and improvement in Patient Global Impression of Change (PGIC) or Clinician Global Impression of Change (CGIC). Results and discussion: Six RCTs were included. Gabapentin 1800 mg/day reduced the 24-h average pain intensity scores [standard mean differences (SMD) À0Á50; 95% confidence interval (CI) À0Á88, À0Á13; I 2 = 86Á3%] and average daily sleep rating scores [weighted mean differences (WMD) À0Á71; 95% CI À1Á11, À0Á32; I 2 = 0%]. Gabapentin treatment yielded an improvement in pain intensity (risk ratio (RR) 1Á88; 95% CI 1Á35, 2Á29; I 2 = 64Á8%; for 50% reduction and RR 1Á43; 95% CI 1Á12, 1Á83; I 2 = 0% for 30% reduction, respectively), PGIC (RR 1Á49; 95% CI 1Á28, 1Á74; I 2 = 0%), and CGIC (RR 1Á58; 95% CI 1Á29, 1Á92; I 2 = 30Á9%). However, gabapentin increased the somnolence (RR 2Á03; 95% CI 1Á39, 2Á98; I 2 = 2%), dizziness (RR 2Á68; 95% CI 1Á95, 3Á69; I 2 = 15%), peripheral oedema (RR 9Á10; 95% CI 3Á23, 25Á60; I 2 = 2%), total adverse effects (RR 1Á28; 95% CI 1Á16, 1Á42; I 2 = 0%) and withdrawal due to adverse events (RR 1Á51; 95% CI 1Á06, 2Á16; I 2 = 6%), but these adverse effects were often mild to moderate.

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Long-term Safety of Gastroretentive Gabapentin in Postherpetic Neuralgia Patients

Abstract: Long-term treatment (up to 24 wk) with G-GR of 1800 mg was well tolerated and associated with little weight gain (< 1 kg) in patients with PHN. No new safety issues emerged with G-GR long-term treatment.

Cited by 5 publications

References 23 publications

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

Relationships Among Adverse Events, Disease Characteristics, and Demographics in Treatment of Postherpetic Neuralgia With Gastroretentive Gabapentin

Efficacy and safety of gabapentin 1800 mg treatment for post-herpetic neuralgia: a meta-analysis of randomized controlled trials

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