Glycopyrrolate for Chronic Drooling in Children

Background: Sialorrhea, or drooling, is seen in the pediatric population, especially in patients with cerebral palsy and other neurodevelopmental disabilities. If medication use is warranted, anticholinergic agents are the drug of choice; however, adverse effects limit their use. Glycopyrrolate, a synthetic anticholinergic that acts at peripheral muscarinic receptors, has been used off-label for excessive drooling in children with neurodevelopmental disabilities for years. Product formulations restricted the use of glycopyrrolate. However, an oral solution was approved by the US Food and Drug Administration for children ages 3 to 16 years with neurologic disorders for chronic severe drooling in 2010; it became available for use in 2011. Objective: This article provides an overview of the pharmacology, clinical efficacy, and tolerability of glycopyrrolate when used for sialorrhea in children. Methods: To evaluate the efficacy and safety profile of glycopyrrolate for the treatment of sialorrhea in children, a comprehensive search was performed of the MEDLINE database (1966 February 25, 2012) and International Pharmaceutical Abstracts as well as references from additional review articles identified. Searches were conducted using the terms glycopyrrolate, sialorrhea, drooling, secretion, and pediatrics. The terms drug-induced and Parkinson disease associated sialorrhea were excluded from the search. The pharmaceutical manufacturer of the oral solution was contacted for medical and study information. Results: Oral bioavailability of glycopyrrolate varies widely, with a median of 3.3%. Mean C-max in children was determined to be 0.37 mu g/mL, and mean Lax was 3.1 hours. The clearance in children ranges from 0.6 to 1.43 L/kg/h. The t(1/2) ranges from 22 to 130 minutes and 19 to 99 minutes in infants and children, respectively. Six studies describing the use of glycopyrrolate for drooling in children were identified. A double-blind, crossover trial of 27 patients (age range, 4-19 years) demonstrated a reduced mean drooling score (modified Teacher's Drooling Scale [1 = never drools to 9 = clothing, hands, and objects frequently become wet]) for glycopyrrolate (mean highest tolerated dose, 0.11 mg/kg) compared with placebo of 1.85 versus 6.33 (P < 0.001). In a parallel study of 36 patients (age range, 3-16 years), 14 of 20 patients randomized to receive glycopyrrolate solution showed improvement in the mean modified Teacher's Drooling Scale score compared with only 3 patients receiving placebo (-3.5 vs -0.1, respectively). Glycopyrrolate was initiated at 0.02 mg/kg per dose orally TID (Max dose: 3 mg) and titrated over a 4-week period. Adverse effects identified in studies include dry mouth (9%-41%), constipation (9%-39%), and behavioral changes (18%-36%). Conclusions: Glycopyrrolate is effective in decreasing sialorrhea in children with cerebral palsy or other neurodevelopmental disabilities. Adverse effects did occur, more frequently at higher doses, and should be monitored. (Clin Ther. 2012;34:735-742) (C) 2012 Elsevier HS Journals, Inc. All rights reserved.