New Drug Review
Glycopyrrolate for Chronic Drooling in Children
Lea S. Eiland, PharmD, BCPS
Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Huntsville, Alabama
ABSTRACT
Background: Sialorrhea, or drooling, is seen in the
pediatric population, especially in patients with ce-
rebral palsy and other neurodevelopmental disabili-
ties. If medication use is warranted, anticholinergic
agents are the drug of choice; however, adverse ef-
fects limit their use. Glycopyrrolate, a synthetic an-
ticholinergic that acts at peripheral muscarinic re-
ceptors, has been used off-label for excessive
drooling in children with neurodevelopmental dis-
abilities for years. Product formulations restricted
the use of glycopyrrolate. However, an oral solution
was approved by the US Food and Drug Administra-
tion for children ages 3 to 16 years with neurologic
disorders for chronic severe drooling in 2010; it be-
came available for use in 2011.
Objective: This article provides an overview of the
pharmacology, clinical efficacy, and tolerability of gly-
copyrrolate when used for sialorrhea in children.
Methods: To evaluate the efficacy and safety pro-
file 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 var-
ies widely, with a median of 3.3%. Mean C
max
in chil-
dren was determined to be 0.37
g/mL, and mean T
max
was 3.1 hours. The clearance in children ranges from
0.6 to 1.43 L/kg/h. The t
½
ranges from 22 to 130 min-
utes and 19 to 99 minutes in infants and children,
respectively. Six studies describing the use of glycopy-
rrolate 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 ϭ never drools
to 9 ϭ 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 Ͻ 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 (Ϫ3.5
vs Ϫ0.1, 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 de-
creasing sialorrhea in children with cerebral palsy or
other neurodevelopmental disabilities. Adverse ef-
fects did occur, more frequently at higher doses, and
should be monitored. (Clin Ther. 2012;34:735–742)
© 2012 Elsevier HS Journals, Inc. All rights re-
served.
Key words: anticholinergic, children, drooling, gly-
copyrrolate, pediatrics, sialorrhea.
INTRODUCTION
Sialorrhea, or drooling, is seen in the pediatric popula-
tion and is defined as saliva that unintentionally goes
beyond the lip margin.
1
Drooling is normal in infants
and decreases as they develop oral motor skills, usually
at ϳ18 months of age. However, the occurrence of
continual drooling after 4 years of age should be eval-
uated.
1
Sialorrhea is most commonly seen in patients
Accepted for publication February 27, 2012.
doi:10.1016/j.clinthera.2012.02.026
0149-2918/$ - see front matter
© 2012 Elsevier HS Journals, Inc. All rights reserved.
Clinical Therapeutics/Volume 34, Number 4, 2012
April 2012 735