Investigational topical anticholinergics in clinical development for the treatment of hyperhidrosis

Figures & data

Table 1. Studies of topical anticholinergics in patients with focal hyperhidrosis

Active agent	Preparation	Disorder	Efficacy	Tolerability
Glycopyrronium bromide
Shaw et al. 1997 [4]	Cream 0.5%	GS	+	+
Hale et al. 2000 [5]	Cream 2%	AH	–	±
Masur et al. 2020 [6]	Cream 0.5%, 1%, 2%	AH	2%: ++ 1%: + 0.5%: ±	2%: ± 1%: ± 0.5%: ±
Abels et al. 2021 [7]	Cream 1%	AH	++	±
Hyun et al. 2015 [8]	Solution 2% in cotton pads	CF	+	+
Baker et al. 2016 [9]	Spray 1%,2%	AH	1%: ± 2%: +	1%: + 2%: +
Umeclimidium
Nasir et al. 2018 [10]	Solution 1.85%	AH	±	+
Oxybutinin Chloride
Nguyen et al. 2018 [13]	Gel 3%	AH	+	±
Artzi et al. 2017 [14]	Gel 10%	AH, PPH	+	+
Millán-Cayetano et al. 2017 [15]	Patch	AH, PPH	±	–
Bergón-Sendín et al. 2016 [16]	Patch	AH, CF, PPH	±	-
Sofpironium bromide
Kirch et al. 2020 [11]	Gel 5%, 10%, 15%	AH	++ (all)	+ (all)
Yokozeki et al. 2021 [12]	Gel 5%	AH	++	±

GS: Gustatory sweating, AH: Axillary hyperhidrosis, CF: Craniofacial hyperhidrosis, PPH: Palmoplantar Hyperhidrosis.

Efficacy

++ Significant sample of participants, double blind design, statistically

significant efficacy compared to placebo.

+ One of the above is not fulfilled.

± Two of the above are not fulfilled.

Tolerability

+Low incidence of significant adverse events that could lead to

discontinuation of treatment.

± Significant incidence of adverse events that could lead to discontinuation

of treatment.

- Verified discontinuation of treatment for a significant number of participants.

Table 2. Comparison and evaluation of available data for the topical anticholinergics under investigation

	Most promising preparation under investigation	Most promising concentration under investigation	Evidence from studies	Pharmacology considerations
Glycopyrronium bromide	Cream and solution	1% Penetration enhancers should probably need to be added to the final formulation	Strong: multiple studies. multicenter, randomized, compared to vehicle design	Minimal blood-brain barrier penetration expected, due to glycopyrronium being highly polarized
Umeclidinium	Solution	1.85%	Poor: One phase II study, few patients, no statistical comparison with vehicle undertaken	Poor penetration of blood-brain barrier has been reported
Sofpiromiuum bromide	Gel	5%	Moderate: Phase II, and Phase III studies, already approved in Japan	Analogue of glycopyrrolate, retrometabolic design, minimal penetration of blood-brain barrier expected
Oxybutinin chloride	Gel	5%	Poor: case series and small studies open label design	Considerable penetration of blood-brain barrier expected due to lipophilicity

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