Trends in First Gabapentin and Pregabalin Prescriptions in Primary Care in the United Kingdom, 1993-2017

Objectives Gabapentin has been increasingly used in various indications in recent years. Despite variable pharmacokinetics, therapeutic drug monitoring (TDM) is scarcely described in other indications than epilepsy. The aim of the study was to investigate the use and pharmacokinetic variability of gabapentin in epilepsy and non‐epilepsy indications and to further evaluate the use of TDM in patients with restless legs syndrome (RLS). Materials & Methods Population‐based data from the Norwegian Prescription Database, retrospective TDM data from the section for Clinical Pharmacology, the National Center for Epilepsy, Norway, and prospective observational data on patients with RLS were used. Results The use of gabapentin increased by 30% from 2014 to 2017 (32 181 to 42 675 users). TDM data from 120 patients showed a 22‐fold pharmacokinetic variability in concentration/dose ratios, and this ratio was elevated in elderly patients (≥65 years). The majority of elderly used gabapentin for non‐epilepsy indications. In patients with RLS, intake in the evening/night only was common due to nocturnal symptoms, in contrast to regular dosing regimens in epilepsy. Thus, drug fasting concentrations do not reflect concentrations at the time of required therapeutic effect. TDM was still found useful in most patients to support dosage increase or evaluate adverse effects. Conclusion Due to extensive pharmacokinetic variability, TDM can benefit patients using gabapentin. Challenges with applying TDM in new indications such as RLS include different dosage regimens and consequently different interpretation of serum concentrations. Thus, TDM should be requested on clear clinical grounds and the service tailored according to the therapeutic indication.

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“…The use of GBP in Norway was shown to gradually increase from 2007 to 2015, 4,5 due to an increase in use in neuropathic pain. 27 27 …”

Section: Use Of Gbp In Norwaymentioning

confidence: 99%

“…4 Increased use has also been demonstrated internationally, with a recent study from United Kingdom finding a large increase in the rate of patients newly treated with GBP from 2007 to 2017. 27…”

Section: Use Of Gbp In Norwaymentioning

confidence: 99%

Therapeutic drug monitoring of gabapentin in various indications

et al. 2019

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“…Parkinson's disease (PD) is a common neurodegenerative disorder, and the major unmet needs of PD are the identification of reliable biomarkers and the development of successful disease-modifying treatments, 2 issues that are basically linked to a better comprehension of the disease pathogenesis. 1,2 Compelling evidence indicates that oxidative stress and neuroinflammation play central roles in the pathophysiology of PD. [3][4][5][6] These processes are critically modulated by the transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of cellular defence.…”

Section: Introductionmentioning

confidence: 99%

“…Gabapentinoids, such as gabapentin and pregabalin, are indicated in neuropathic pain and epilepsy. Recent US and European data have shown that their use tripled during the last decade, and there has been a high level of off‐label prescriptions and misuse . Although side effects, such as somnolence, dizziness, and ataxia, are usually mild, long‐term adverse effects are unknown.…”

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confidence: 99%

“…Recent US and European data have shown that their use tripled during the last decade, and there has been a high level of offlabel prescriptions and misuse. [1][2][3] Although side effects, such as somnolence, dizziness, and ataxia, are usually mild, long-term adverse effects are unknown. Their pharmacodynamic mechanisms are complex and poorly understood, which should lead to vigilance in clinical practice.…”

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confidence: 99%

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Parkinsonism Associated with Gabapentinoid Drugs: A Pharmacoepidemiologic Study

et al. 2019

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Background Use of gabapentinoids is increasing. Following recent case reports, we investigated a putative risk of parkinsonism with pregabalin or gabapentin. Methods A disproportionality analysis of 5,653,547 individual case safety reports in the World Health Organization individual case safety report database, VigiBase, compared all patients with parkinsonism who were receiving gabapentinoids with other patients. Results are shown as reporting odds ratios and the information component, an indicator of disproportionate Bayesian reporting. Sensitivity analyses included comparisons with drugs used for similar indications (amitriptyline, duloxetine) and exclusion of drugs that induce parkinsonism. Results Among 5,653,547 reports, 4925 parkinsonism reports were found with pregabalin and 4881 with gabapentin. Gabapentin and pregabalin were associated with increased reporting odds ratio (2.16 [2.10–2.23], 2.43 [2.36–2.50]). Similar trends were found using information components after excluding drugs that induce parkinsonism and for pregabalin compared with amitriptyline or duloxetine. Conclusions This study found that gabapentinoids (particularly pregabalin) can be associated with parkinsonism. © 2019 International Parkinson and Movement Disorder Society

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2019

JAMA

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used may no longer meet diagnostic criteria on subsequent testing (or conversely be reassigned from normal to having gestational diabetes). Childhood overweight and obesity is defined by body mass index (BMI); however, BMI in the overweight range sometimes reflects high lean body mass more than adiposity and thus is an imprecise measure of adiposity. Nevertheless, since height and weight are routine clinical measures, BMI z score is typically used clinically as an index of adiposity. The BMIbased childhood overweight and obesity cutoffs 2 were therefore used to power our study. We concur that the nonsignificant fully adjusted odds ratio of 1.21 (95% CI, 1.00-1.46) for the association between gestational diabetes and childhood overweight and obesity may have been related to not meeting our recruitment target. Anticipating the potential limitation of the overweight and obesity outcome and noting the importance of fully addressing contextual factors when drawing scientific conclusions using measures of statistical significance, 3 the HAPO Follow-up Study specified a priori 4 additional secondary measures of childhood adiposity as part of the study design (Table 4 in the article). These included (1) obesity as defined by BMI, (2) percentage of body fat determined by air displacement plethysmography, (3) sum of skinfolds, and (4) waist circumference. In contrast to the overweight and obesity outcome, these 4 outcomes were all significantly associated with gestational diabetes in a fully adjusted model that included maternal BMI. Arguably, the association of gestational diabetes with these more specific measures of childhood adiposity may be as important as the nonsignificant association of gestational diabetes with overweight and obesity. When considered together, our results suggest an association between gestational diabetes as defined by IADPSG criteria and later childhood obesity and adiposity. Requiring more stringent criteria to identify gestational diabetes would narrow the application of the results to primary prevention efforts and diminish the public health implications.

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Trends in First Gabapentin and Pregabalin Prescriptions in Primary Care in the United Kingdom, 1993-2017

Abstract: Given the safety concerns of gabapentinoids and the lack of robust evidence supporting their efficacy in cases of nonneuropathic pain, 6 caution is necessary when prescribing gabapentinoids, especially among patients also prescribed opioids.

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Therapeutic drug monitoring of gabapentin in various indications

Therapeutic drug monitoring of gabapentin in various indications

Parkinsonism Associated with Gabapentinoid Drugs: A Pharmacoepidemiologic Study

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