Glycopyrrolate for Hyperhidrosis
Yes, glycopyrrolate is an effective and FDA-approved treatment for primary hyperhidrosis, available in both topical and oral formulations. 1
FDA-Approved Topical Formulation
Glycopyrronium tosylate (topical glycopyrrolate) received FDA approval in June 2018 specifically for primary axillary hyperhidrosis. 1 This represents the highest-quality evidence supporting its use, as it is based on rigorous phase 3 randomized controlled trials.
Efficacy Data from Pivotal Trials
In the ATMOS-1 and ATMOS-2 phase 3 trials, topical glycopyrronium tosylate 3.75% applied once daily demonstrated significantly superior efficacy compared to vehicle, with 59.5% of patients achieving a clinically meaningful response (≥4-point improvement in sweating severity) versus 27.6% with vehicle (P < .001). 2
Gravimetric sweat production was reduced by an average of 107.6 mg/5 minutes from baseline, significantly more than vehicle at 92.1 mg/5 minutes (P < .001). 2
The medication was generally well tolerated with mostly mild to moderate adverse effects that infrequently led to discontinuation. 2
Topical Application Sites Beyond Axillae
While FDA approval is specifically for axillary hyperhidrosis, clinical evidence supports off-label topical use for other anatomical sites:
Craniofacial hyperhidrosis: A 0.5% glycopyrrolate solution applied topically to the face and forehead demonstrated significant reduction in facial sweating with minimal adverse effects, maintaining efficacy even after multiple face washings. 3
Gustatory hyperhidrosis: Topical glycopyrrolate 1.5-2% showed excellent results (complete resolution of sweating after eating spicy foods) in 77% of patients with post-sympathectomy gustatory hyperhidrosis, with only mild side effects including dry mouth and sore throat. 4
Oral Glycopyrrolate for Hyperhidrosis
Oral glycopyrrolate represents an alternative systemic approach, particularly useful for generalized or multifocal hyperhidrosis:
Seasonal dose adjustment is critical for optimal outcomes: Patients who adjusted their oral glycopyrrolate dose according to seasonal temperature variations were significantly more likely to report an "excellent" response after 12 months of treatment compared to those maintaining a fixed dose. 5
Patients with palmar and plantar hyperhidrosis showed greater propensity to benefit from seasonal dose adjustments. 5
Oral glycopyrrolate is typically considered after failure of other oral anticholinergics like oxybutynin. 5
Key Advantages of Glycopyrrolate
Glycopyrrolate has a quaternary ammonium structure that prevents blood-brain barrier penetration, making it significantly less likely to cause central nervous system side effects such as delirium, sedation, or confusion compared to atropine or scopolamine. 6, 7 This pharmacological property is particularly important for patients requiring chronic therapy or elderly patients. 6
Common Pitfalls and Practical Considerations
Anticholinergic side effects including dry mouth, blurred vision, urinary retention, and constipation can occur with both topical and oral formulations, though topical application minimizes systemic exposure. 7
For oral therapy, do not maintain a fixed year-round dose; instead, counsel patients to increase dosing during warmer months when sweating naturally increases. 5
Topical glycopyrrolate is more effective at preventing new secretion formation than eliminating existing sweat, so application should be proactive rather than reactive. 7
The topical formulation requires daily application for sustained benefit, with recurrence of hyperhidrosis occurring within 2 days of discontinuation. 3