CMC may have a congenital or acquired disease with a severe neurologic and functional impairment and with a complete dependence for daily life activities; the presence of tracheostomy with or without mechanical ventilation, the presence of gastrostomy for enteral feeding, of a central venous access as the need of frequent aspirations of saliva during the day characterized this population [9, 10]. Especially in this subset of patients, the drooling control could represent a major goal in their clinical management. In fact, the drooling represents a major issue in patients with neurological impairment for its clinical and social impact. These children are at risk of saliva aspiration which can cause recurrent pneumonia and impairment in the gastric acid reflux removal related with esophageal dysmotility and esophagitis. The accumulation of saliva in the mouth can increase oral infections and damage the teeth. Moreover, the halitosis has a bad impact on social relationship.
Medical treatment is based on anticholinergic drugs as transdermal scopolamine, benzotropine and GLY [2,3,4,5,6,7,8, 12, 13]. GLY (Glycopyrrolate or glycopyrronium bromide) is a synthetic quaternary ammonium anticholinergic agent with poor blood–brain barrier penetration and consequently has limited and rare central effects. GLY was approved for clinical use in 1961 for peptic ulcer disease in adults. Actually, the oral GLY formulation was approved by the United States Food and Drug Administration (FDA) to treat drooling in children aged 3–16 years [3,4,5,6,7,8,9,10,11,12,13,14]. Orally GLY has relatively low and variable bioavailability influenced by high-fat meal that significantly decreased the absorption and excreted largely via the kidneys. After oral administration, GLY half-life is about 3 h and was present in plasma for < 12 h, following oral administration [14]. The suggested daily dosage is 0.02–0.1 mg/kg in 3 daily dose [ 3–8].
Five studies reported on GLY use for the treatment of drooling in children with cerebral palsy and other conditions with neurological impairment; four are prospective studies [5, 6, 8, 15, 16] while one a retrospective review [7]. Different dosages were proposed but almost the daily dosage was fractionated over three doses with limited toxicities and efficacy in reducing drooling in a mixed population including children with more than 3 years of age and young adults. In the randomized double-blind, dose-ranging trial [8], 39 children were treated according to two dosage regimens based on weight. Children less than 30 kg were started at 0.6 mg, with weekly increases to 1.2 mg, 1.8 mg, and 2.4 mg, whereas children over 30 kg were started at 1.2 mg, with weekly increases to 1.8 mg, 2.4 mg, and 3.0 mg. In the most recent prospective randomized placebo-controlled phase III study [15], GLY resulted to be significantly superior to placebo in reducing drooling in children aged 3–16 years affected by cerebral palsy or other neurological conditions associated with drooling problem. The dose used ranged from 0,02 mg/kg to 0,1 mg/kg accounting of the wide oral bioavailability range.
We present a case report of CMC treated with GLY before 3 years of age and with a median weight of 9.8 kg (range 3.5–22 kg). GLY seems effective in decreasing drooling with an overall response of about 94% with a statistically significant reduction of mean value of Drooling Impact Scale considered between baseline and follow-up (P < 0.001). The treatment was well tolerated with limited toxicities and a prolonged administration, mean treatment duration was of 31.5 months (range 1–69 months).
The median daily starting dose of 0.06 mg/kg (range 0.02–0.21 mg/kg) up to 0.07 mg/kg (range 0.02–0.28 mg/kg) in 3 daily dose with a high dose/kg for low weight patients due to the dosage adjustment using the 0.5 mg tablets. In fourteen patients, the starting dose controlled drooling without no need of dose/kg increase. We observed a side effects occurrence of about 5%; probably the limited side effect occurrence could be related to the young age of patients. It should be also considered that the most frequent side effects of GLY are dry mouth and thick secretions, both difficult to report in this age group.
Although our experience is limited, this is the first prospective case report reporting on the GLY use for drooling control in a population of CMC with severe neurological impairment under 3 years of age. An objective measure was used to confirm efficacy of the treatment. GLY is an effective drug and can be used without major complications in this age group for a long period with important social and medical implications. Further prospective and comparative studies are needed to confirm the safety of GLY and its efficacy in younger population. Moreover, the highly variable pharmacokinetics should be considered in a prospective study.
