The US Food and Drug Administration approved glycopyrronium tosylate (QBREXZA) in 2018 for the topical treatment of primary axillary hyperhidrosis in adults and pediatric patients 9 years of age and older. It is the first new clinical treatment for hyperhidrosis since the approval of Botox 15 years ago, according to David M. Pariser, MD, professor of dermatology at Eastern Virginia Medical School in Norfolk, VA, in an interview with The Dermatologist.
A topical anticholinergic, the therapy was found to effectively treat participants with hyperhidrosis in 2 phase 3 clinical trials: ATMOS-1 and ATMOS-2.1
“One of the concerns of any clinical trial is adverse events and how to identify and manage them,” said Dr Pariser. He and his colleagues conducted an open-label extension study to assess adverse events associated with glycopyrronium tosylate, specifically examining the rates of ones known to be associated with anticholinergic therapies. These include dry mouth, mydriasis, blurred vision, and urinary retention/hesitation.
Study Design and Results
A total of 550 participants aged 9 years and older with primary axillary hyperhidrosis who were enrolled in ATMOS-1 and ATMOS-2 trials were included in the study. In the trials, participants received either glycopyrronium tosylate or vehicle for 4 weeks. Those who completed the trials with 80% or higher compliance were given the option to enroll in the open-label extension study and receive glycopyrronium tosylate for up to 44 weeks. Participants were assessed at baseline, and weeks 2, 4, 8, 12, 16, 20, 28, 36, and 44. Treatment-emergent adverse events were recorded throughout the study using open-ended questions.
The most common adverse event associated with anticholinergics was dry mouth (16.9%), followed by blurred vision (6.7%), application site pain (6.4%), nasopharyngitis (5.8%), mydriasis (5.3%), urinary hesitation (4.2%), nasal dryness (3.6%), and dry eyes (2.9%). According to Dr Pariser, these findings were not surprising. “When we give anticholinergics systemically, which is standard of care although off-label, virtually everyone gets dry mouth,” he said. Adverse events, including ones associated with anticholinergics, were reported as mild or moderate, and most resolved within 3 to 14 days.
In addition, adverse events decreased over the course of the 44-week extension period, with the majority occurring within the first 3 months of treatment. “This is an indication that patients were able to manage the drug,” said Dr Pariser. The management of these events included dose interruptions (stopping the drug for a day or 2), dose frequency alterations (every other day), drug withdrawal, or no action. Few participants (n=44) discontinued the study, but the majority did not utilize dose reduction or frequency alteration prior to discontinuing treatment.
Management of Adverse Events
Each of the adverse events associated with anticholinergic therapy can be managed in various ways. For example, some patients experienced mydriasis and blurred vision after accidentally exposing their eyes to the therapy.
“One the first instructions we give patients who apply this drug topically with their hand is to be sure to wash it thoroughly so that they do not get any of the therapy in their eyes,” said Dr Pariser. If patients do get the therapy in their eyes, their dermatologist can reassure them that mydriasis goes away on its own in a couple of hours or days, added Dr Pariser.
“It is important to let people know up front that, because this is an anticholinergic drug, there is some systemic absorption and a number of patients will experience these effects,” said Dr Pariser.
Oral anticholinergics are prescribed for patients with hyperhidrosis, added Dr Pariser, and among those patients, everyone experiences some adverse effect. These can be managed by dose interruption or changing the frequency of application to every other day.
The only adverse event that may require immediate treatment is urinary retention, “which could be handled on an emergent basis,” said Dr Pariser. However, this is not likely if the patient is warned about the potential for urinary hesitancy/retention, he added. Dose interruption and reduced frequency can also address urinary hesitancy and prevent retention.
This study validates the efficacy of topical glycopyrronium tosylate for patients with primary axillary hyperhidrosis. “Although there was some systemic absorption, the therapeutic effect was not much different for systemic absorption verses topical application suggesting it is working topically,” said Dr Pariser. While this is a major breakthrough in the treatment of hyperhidrosis, more studies are needed to determine the optimal strategy for treatment and whether this therapy is effective for hyperhidrosis affecting the hands, feet, face, scalp, breasts, groin, and other parts of the body.
For example, the skin on the hands and feet is thicker than under the arms. “We are not sure whether the absorption or its therapeutic effect is going to be the same or different,” said Dr Pariser. While this therapy was not studied in those areas, patients will still use this therapy on other areas affected by hyperhidrosis, added Dr Pariser, thus we give them some instructions for other parts of the body. For example, he and his colleagues are reluctant to use the therapy on the face and scalp due to the risk of getting some in the eyes and warn patients about the potential adverse events associated with this use. Future studies are needed to determine the efficacy, appropriate amount, and frequency of dosing for other areas of the body.
Additionally, Dr Pariser noted that patients, regardless of whether they had an adverse event, have reported not using the therapy every day and still experiencing good improvement.
“In the real world, patients are going to use this as they feel they need it,” said Dr Pariser. “Hyperhidrosis tremendously affects their quality of life, self-image, and relationships. When patients know they that there is a treatment for them that works, it empowers them to feel as though they can control the process. Some patients will decide that they do not need treatment all of the time and prefer that option.”
As more patients with hyperhidrosis use topical glycopyrronium tosylate, more research is needed to determine the real-world use of this therapy and whether dosage and frequency can be adjusted to suit patients’ needs, as well as its efficacy on other areas of the body.
1. Pariser DM, Drew J, Gopalan R, Hebert AA. An evaluation of anticholinergic adverse events with long-term use of topical glycopyrronium tosylate, a treatment for primary axillary hyperhidrosis. Presented at: American Academy of Dermatology Annual Meeting; March 1-5, 2019. Washington, DC.