Glycopyrronium

Glycopyrronium is an anticholinergic agent that is used to treat hyperhidrosis (Glaser DA et al. 2019), COPD and in anesthesia. The active ingredient is a long-acting acetylcholine receptor antagonist (long-acting muscarinic antagonist, LAMA).

Glycopyrronium is a long-acting muscarinic receptor antagonist that binds primarily to the M1 and M3 receptors. When used locally in the airways, glycopyrronium relaxes the smooth muscles of the bronchi by preventing the bronchoconstrictive effect of acetylcholine on the smooth muscle cells of the airways by blocking M1 and M3 receptors. Glycopyrronium is characterized by a long duration of action and only needs to be inhaled once a day. The secretion-inhibiting effect of glycopyrronium is also due to the inhibition of acetylcholine.

Absorption: In adults, a topical dose of 66 mg glycopyrronium reaches a Cmax of 0.08 ± 0.04 ng/ml, with a Tmax of one hour and an AUC0-24 of 0.88 ± 0.57 h*ng/ml.

Inhaled glycopyrronium is about 40% bioavailable. A 25-µg inhalation solution achieves a Cmax of 34.5 pg/ml, with a Tmax of < 20 minutes and an AUC0-inf of 255 h*pg/ml.

An intramuscular dose of 8 µg/kg achieves a Cmax of 3.47 ± 1.48 µg/l, with a Tmax of 27.48 ± 6.12 minutes and an AUC of 6.64 ± 2.33 h*g/l.

Oral glycopyrronium has highly variable pharmacokinetics, reaching a mean Cmax of 0.318 ng/ml, a Tmax of 3.1 hours and an AUC0-24 of 1.74 h*ng/ml.

Glycopyrronium is 38-44% protein-bound in plasma. It is bound to serum albumin, alpha-1-acid glycoprotein and other plasma proteins.

Metabolism: Glycopyrronium is hydrolyzed to the inactive M9 metabolite. Metabolism is mediated primarily by CYP2D6 and to a lesser extent by CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP3A4.

Elimination: 85% of an intravenous dose was recovered in urine and < 5% in bile. > 80% of the recovered dose is the unchanged parent substance. The remainder is excreted as an inactive M9 metabolite. The mean half-life of oral glycopyrronium is 3.0 hours.

The active substance glycopyrronium is used in adults with COPD for bronchodilation by inhalation. Glycopyrronium is also used parenterally in preparation for anesthesia to reduce the secretion of saliva, mucus and gastric juice. Other areas of application include the treatment and prophylaxis of bradycardia during operations. Glycopyrronium is also used to reduce the sometimes severe side effects of anti-muscle relaxants such as neostigmine and pyridostigmine. A more recent indication is hyperhidrosis (Griffo R et al. 2025).

Common side effects of inhaled glycopyrronium include headaches, dry mouth and sleep disorders. There is also an increased risk of inflammation of the nasopharynx, gastrointestinal infections and urinary tract infections.

The most dangerous side effect of intravenous administration of glycopyrronium is cardiac arrhythmia. These occur primarily after the administration of high doses in combination with neostigmine and pyridostigmine.

Glycopyrronium in the form of the one-percent cream must not be used for hyperhidrosis in cases of hypersensitivity to the active substance or any of the other ingredients and in diseases that may be aggravated by the anticholinergic effect of Axhidrox, such as:

• glaucoma
• paralytic ileus
• unstable cardiovascular status with acute bleeding
• severe ulcerative colitis
• ulcerative colitis complicated by toxic megacolon
• myasthenia gravis
• Sjögren's syndrome

The drug should be used with caution in patients with gastroesophageal reflux disease, glaucoma, obstruction of the bladder outflow tract and heart failure.

^Axhidrox®, a one-percent therapeutic agent (cream application) with glycopyronium bromide for the local treatment of hyperhidrosis, has been available since 2022 (Abels C et al. 2021). Topical glycopyrronium tosylate also showed antihyperhidrotic efficacy in several studies (ATMOS-1/NCT02530281, ATMOS-2/NCT02530294) (Pariser DM et al. 2019).

1. Abels C et al. (2021) A 1% glycopyrronium bromide cream for the topical treatment of primary axillary hyperhidrosis: efficacy and safety results from a randomized, controlled phase IIIa study. Br J Dermatol 185:315-322.
2. Glaser DA et al. (2019) A 44-week, open-label study to evaluate the safety and efficacy of topical glycopyrronium tosilate in patients with primary axillary hyperhidrosis. Am J Clin Dermatol 20:593-604.
3. Griffo R et al. (2025) Sweating in the GRiff-when surgery can cure. Derma aktuell 06:8-10
4. Pariser DM et al. (2019) Topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: patient-reported outcomes of the randomized, controlled phase III ATMOS-1 and ATMOS-2 trials. Am J Clin Dermatol 20:135-145.