Systemic Medication

Systemic medications may be used for the treatment of generalized or focal hyperhidrosis[145]. They may be useful for patients with cranio-facial hyperhidrosis, focal hyperhidrosis affecting large areas such as the back, multifocal hyperhidrosis, hyperhidrosis that is not satifactorily treated with other methods, or temporary, short-term event-specific hyperhidrosis management (ex. for a wedding, speech, or performance).

Additionally, experienced practitioners in hyperhidrosis care (including IHhS Board of Directors members) report effective use of systemic medications as adjunctive therapy to help patients find more relief from hyperhidrosis symptoms than other treatments are providing alone. For example, medications may be used in addition to antiperspirants, iontophoresis (or in the water baths of iontophoresis), and/or injectables.

The drugs currently used for systemic treatment of hyperhidrosis have not yet been studied in controlled trials specifically for excessive sweating. Their use, instead, is based on anecdotal evidence and much practitioner experience. They are not approved by the US Food and Drug Administration, at this time, for the treatment of hyperhidrosis. Keep in mind, also, that at the doses likely to inhibit hyperhidrosis, side effects can be limiting.[134]

The most commonly used agents for excessive sweating are anticholinergics, which block the sympathetic stimulation of eccrine glands by inhibiting the action of acetylcholine at the synapse.[19] Use of these drugs can be limited, however, by the common side effects of the anticholinergic class—dry mouth, urinary retention, constipation, and visual disturbances such as mydriasis and cycloplegia.[9,19] It may be possible to manage such side effects by adjusting the dose. It should be noted, also, that studies (in JAMA Neurology 2016 and JAMA Internal Medicine 2015) have reported a potential link between the development of dementia and/or brain atrophy and long-term, high-level anticholinergic use in patients over the age of 65.

Anticholinergics used for hyperhidrosis include glycopyrrolate, propantheline, glycopyrronium bromide, oxybutynin, and benztropine.[19] Anticholinergic therapy is generally not recommended in patients with glaucoma (especially narrow-angle glaucoma) and those who have impaired gastric emptying or a history or symptoms of urinary retention. Patients should be aware of risks of overheating when using anticholinergics. Athletes, people who work outdoors and anyone who may potentially cause themselves injury by becoming overheated must use extra care when considering these treatments. Patients or parents of children taking the medication must remain aware of temperature, water intake, exertion, and any symptoms of overheating. 

When considering anticholinergic options note that glycopyrrolate is a preferred anticholinergic in part because it less likely than others in the class to cross the blood-brain barrier. Glycopyrrolate is not on the Beers list of potentially inappropriate medications for the elderly put out by the American Geriatric Society and is the only anticholinergic not on that list. 

Two common anticholinergic medications are available in liquid formulations, which can helpful for children who suffer from hyperhidrosis. One is a liquid form of glycopyrrolate (Cuvposa) indicated to reduce drooling in pediatric cerebral palsy patients. The other is oxybutynin in a liquid indicated for pediatric patients with certain bladder and urinary conditions.

Another option for anyone with difficulty swallowing is recently-launched (2022) Dartisla ODT, the first FDA-approved orally disintegrating tablet of glycopyrrolate. Dartisla ODT is FDA-approved as an add-on treatment to reduce symptoms of peptic ulcer, but may be prescribed off-label for patients with excessive sweating. Dartisla comes as a freeze-dried tablet that disperses almost instantly in the mouth, and is absorbed by mucous membranes. Each tablet of Dartisla ODT is 1.7mg of glycopyrrolate, which is bioequivalent to 2mg of oral glycopyrrolate. If prescribing Dartisla ODT, educate patients to handle doses with dry hands as the tablets will disintegrate upon any contact with moisture. Blister packs make it possible to open a dose and drop it into the mouth. Patients can receive Dartisla ODT for as little as $0 through Phil, an online pharmacy, or as little as $20 at other pharmacies.

Some physicians have had success treating palmar and/or plantar hyperhidrosis by adding a crushed anticholinergic tablet to iontophoresis water. The ODT form of glycopyrrolate (Dartisla ODT) may show itself to be convenient for this purpose.

When stressful situations are a trigger for hyperhidrosis, use of an anticholinergic agent or a benzodiazepine prior to an event likely to provoke anxiety may be helpful.[19] Long-term use of benzodiazepines such as diazepam is limited by development of dependency,[9] and many patients cannot tolerate the sedative effects of these drugs.[34] Some patients are able to take diazepam 5 mg at bedtime for several weeks to get used to its sedating effect and then use it as needed for anxiety-provoking events.[34]

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