Safety and efficacy of glycopyrrolate oral solution for management of pathologic drooling in pediatric patients with cerebral palsy and other neurologic conditions.

BACKGROUND: The purpose of this study was to assess the safety and efficacy of oral glycopyrrolate solution 1 mg/5 mL for 24 weeks in pediatric patients with chronic moderate-to- severe drooling associated with cerebral palsy and other neurologic conditions.

METHODS: In this multicenter, open-label, 24-week study, males and females aged 3-18 years weighing at least 27 lb received oral glycopyrrolate solution, starting at 0.02 mg/kg three times daily and titrated in increments of 0.02 mg/kg every 5-7 days for 4 weeks to an optimal maintenance dose or a maximum dose of 0.1 mg/kg, but not exceeding 3 mg three times daily. Safety was assessed by description and tabulation of all adverse events. The primary efficacy endpoint was response, defined as at least a three-point change from baseline to week 24 on the modified Teacher's Drooling Scale.

RESULTS: Of 137 intent-to-treat participants, 10 (7.3%) received the maximum dose of 0.1 mg/kg three times daily; 122 (89%) had at least one treatment-emergent adverse event, 47% related to oral glycopyrrolate solution, with most being mild-to-moderate in intensity. The most commonly reported treatment-emergent adverse events were constipation (20.4%), vomiting (17.5%), diarrhea (17.5%), pyrexia (14.6%), dry mouth (10.9%), flushing (10.9%), and nasal congestion (10.9%). Nineteen patients (13.9%) discontinued treatment due to an adverse event, but no adverse event was specifically associated with discontinuation. Two patients had clinically significant toxicity grade shifts, one each in platelet count and calcium concentration. No deaths occurred on treatment; deaths of three patients (multisystem organ failure, anoxic encephalopathy, and aspiration pneumonia) within 30 days of their last dose were not considered to be treatment-related. At 24 weeks, 52.3% (95% confidence interval 43.7-60.9) of patients were responders, with at least a three-point decrease in modified Teacher's Drooling Scale from baseline, with 83.5% of parents/caregivers and 85.8% of investigators rating oral glycopyrrolate solution as being worthwhile.

CONCLUSION: Oral glycopyrrolate solution 1 mg/5 mL for chronic moderate-to-severe drooling associated with cerebral palsy or other neurologic conditions was well tolerated over 24 weeks by pediatric patients aged 3-18 years.