Limited Systemic Exposure with Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis

Abstract

Background Glycopyrronium tosylate (GT; Qbrexza ® [glycopyrronium] cloth, 2.4%) is a topical anticholinergic approved (USA) for primary axillary hyperhidrosis in patients aged ≥ 9 years. Objective The objective of this study was to compare the pharmacokinetics and safety of GT to oral glycopyrrolate (phase I study) and assess the relationship between glycopyrronium pharmacokinetics and anticholinergic-related adverse events or efficacy with population pharmacokinetics using data from two phase II studies. Methods In the phase I study, study staff applied GT to axillae of patients with primary axillary hyperhidrosis (aged 9–65 years) once daily (5 days); oral glycopyrrolate was administered to healthy adults (aged 18–65 years) every 8 hours (15 days). In the phase II studies (NCT02016885 [20 December, 2013], NCT02129660 [2 May, 2014]), adults with primary axillary hyperhidrosis applied topical glycopyrronium (0.8–3.2%) or vehicle to axillae once daily (4 weeks). Pharmacokinetic and adverse event data were collected in all studies. Results Glycopyrronium pharmacokinetic parameters were similar between adult and pediatric patients treated with GT; there was no evidence of accumulation. Systemic absorption of glycopyrronium was lower with GT vs oral glycopyrrolate. No anticholinergic-related adverse events occurred with GT in the phase I study, while dry mouth and nasal dryness occurred with oral glycopyrrolate; anticholinergic adverse events occurred in the phase II studies. In the population pharmacokinetic analysis, frequency/severity of anticholinergic-related adverse events increased with higher glycopyrronium concentration; no relationship was observed between efficacy and pharmacokinetic measures. Conclusions These studies indicate limited absorption of GT compared to oral glycopyrrolate and a low risk of anticholinergic adverse events with proper GT administration when following instructions for use (wipe each underarm once with same cloth, wash hands, avoid ocular contact). Supplementary Information The online version contains supplementary material available at 10.1007/s40262-020-00975-y.

Pharmacokinetic profile data of glycopyrronium bromide 1% cream beyond 2 weeks are important

“…The authors reported increases in the mean plasma GP levels in the first 7-8 days of treatment, a small decline for the GPB 0Á5% and 1% cream during the next 7 days of treatment, and a more pronounced decline 7 days after the treatment period. 2 Interestingly, these values were spread out over a relatively large range. In the same phase Ib study, the maximum GP exposure, as measured by the peak concentration (C max ), were apparently below the respective values observed after oral administration, but the time to maximum plasma concentration (T max ) and the area under the curve (AUC) are not available.…”

“…In 2021, Pariser et al . reported the pharmacokinetic (PK) profile of GP tosylate wipes applied by patients with hyperhidrosis for 4 weeks with a 2‐week off‐drug follow‐up 4 . In view of the likely systemic absorption of topical anticholinergic agents, the possible risks of their long‐term use and the potential interindividual variability, especially in elderly patients, we believe that data on the PK profile of the GPB 1% cream formulation for a time period beyond 2 weeks are of great importance in real‐world practice and need to be considered and critically evaluated in an appropriately extended clinical trial programme.…”

Pharmacokinetic profile data of glycopyrronium bromide 1% cream beyond 2 weeks are important: reply from the authors

“…COVID-19 ARDS-prone individuals, such as those aged over 70 years, men and those with comorbid conditions, including obesity, diabetes or heart disease, will have reduced natural killer (NK) cell function compared with people without these characteristics. 2 A critical reduction in NK cell function would lead to immune dysregulation and thus aberrant response to a stimulus (SARS-CoV-2 infection in the case of COVID-19) and overproduction of cytokines, including interleukin (IL)-1b, IL-8, IL-17, tumour necrosis factor (TNF)-a and granulocytemacrophage colony-stimulating factor. Such cytokines would in turn promote neutrophil activation, with an increased neutrophil/lymphocyte ratio (NLR) and monocytosis.…”

“…The PK data (C max ) of GP are predictive of anticholinergic adverse events (AEs) following topical application regarding frequency and severity. 2 As the frequency of systemic, anticholinergic AEs was lower after treatment with GPB cream than with GPT-containing wipes, 3,4 plasma concentrations after topical application of GPB cream are unlikely to exceed those of GPT-containing wipes.…”

“…DEAR EDITOR, Gregoriou et al have asked for systemic pharmacokinetic (PK) data beyond 2 weeks after the topical application of glycopyrronium (GP) bromide (GPB)-containing cream for treatment of primary axillary hyperhidrosis, 1 compared to another recently approved GP tosylate (GPT)-containing topical product. 2 The active pharmaceutical moiety of both GPB and GPT is GP. A phase Ib study of GPB cream revealed a dose-dependent increase in GP in plasma.…”