ESUOM15: Hypersalivation: oral glycopyrronium bromide
This is information from a NICE 'Evidence summary: new medicines', and is not NICE guidance. The complete commentary is available at http://publications.nice.org.uk/esnm15
Key points from the evidence
There is moderate evidence that oral glycopyrronium bromide (tablets and solution or suspension) reduces hypersalivation (sialorrhoea) or drooling in children and young people with a neurological condition, and adults with Parkinson's disease, compared with placebo. There is also limited evidence of its efficacy in adults with schizophrenia and clozapine-induced hypersalivation. The most commonly reported adverse effects of oral glycopyrronium bromide are antimuscarinic, for example dry mouth. There is no evidence of its long-term efficacy or safety in treating hypersalivation.
Regulatory status: unlicensed.
Glycopyrronium bromide is an antimuscarinic drug that can potentially reduce salivary secretions. This evidence summary describes the efficacy and safety of oral preparations of glycopyrronium bromide (tablets and solution or suspension) when used to treat hypersalivation in adults, children and young people. Hypersalivation is the excessive production of saliva that can cause 'chronic drooling' or 'problem drooling'.
Oral preparations of glycopyrronium bromide (tablets and solution or suspension) are not licensed in the UK. Therefore, using these preparations, which are either imported or prepared by 'specials' manufacturers, for treating hypersalivation would be unlicensed. In 2010, glycopyrrolate (glycopyrronium bromide) 1 mg/5 ml oral solution was licensed in the USA to treat chronic severe drooling in children and young people aged 3–16 years with a neurological condition.
Two double-blind, placebo-controlled, randomised controlled trials (RCTs) were identified that examined the efficacy and safety of oral glycopyrronium bromide for treating hypersalivation in children and young people with a neurological condition (Mier et al. 2000 and Zeller et al. 2012a), and 1 double-blind, placebo-controlled RCT in adults with Parkinson's disease (Arbouw et al. 2010). An additional RCT (Liang et al. 2010) was identified comparing oral glycopyrronium bromide with the centrally acting antimuscarinic biperiden (unlicensed use) for treating clozapine-induced hypersalivation in adults with schizophrenia. All of the identified trials were small, with fewer than 40 participants in each trial, and were short term (8 weeks or less).
The 2 RCTs in children and young people with a neurological condition (predominantly cerebral palsy) showed that oral glycopyrronium bromide significantly improved drooling after 8 weeks of treatment. The dosage of glycopyrronium bromide was titrated and dependent on weight in these trials, up to a maximum of 3 mg per dose given 3 times daily. In 1 of the trials (Mier et al. 2000), the mean parent- or carer-reported drooling score was significantly improved from severe drooling to no drooling or mild drooling with glycopyrronium bromide; drooling remained severe with placebo. In the other trial (Zeller et al. 2012a), there was a significant clinical improvement in drooling from baseline to 8 weeks in 73.7% of children and young people receiving glycopyrronium bromide compared with 17.6% receiving placebo.
The RCT in adults with Parkinson's disease (Arbouw et al. 2010) showed a significant improvement in drooling score with 1 week of glycopyrronium bromide 1 mg 3 times daily compared with placebo.
The RCT in adults with schizophrenia and clozapine-induced hypersalivation (Liang et al. 2010) showed that drooling improved with either oral glycopyrronium bromide 1 mg twice daily or oral biperiden 2 mg twice daily (a centrally acting antimuscarinic agent) for 4 weeks. Drooling significantly improved from baseline with both medicines but glycopyrronium bromide was superior. Participants taking biperiden had a significant reduction in Mini Mental State Examination (MMSE) scores; there were no significant differences from baseline in MMSE scores with glycopyrronium bromide.
Glycopyrronium bromide was associated with more reported adverse effects than placebo in the 2 trials in children and young people with a neurological condition (Mier et al. 2000 and Zeller et al. 2012a ), but statistical significance was not reported. In the Mier et al. (2000) trial, 7 of 36 people stopped treatment while taking glycopyrronium bromide, compared with 1 of 36 people while receiving placebo. In the Zeller et al. (2012a) trial, 1 participant in each group stopped treatment because of adverse effects occurring during treatment.
Additional safety and adverse event warnings are included in the labelling of the US product, Cuvposa (glycopyrrolate [glycopyrronium bromide] 1 mg/5 ml oral solution), which is licensed to treat chronic severe drooling in children and young people aged 3–16 years with a neurological condition. Cuvposa is contraindicated in children and young people with medical conditions that preclude antimuscarinic (anticholinergic) therapy and in people taking concomitant oral forms of potassium chloride.
Constipation is listed as a dose-limiting adverse reaction in the Cuvposa label. Other adverse effect warnings include intestinal pseudo-obstruction (that may present as abdominal distension, pain, nausea or vomiting) and incomplete mechanical intestinal obstruction (that may present as diarrhoea). The most commonly reported adverse effects listed, with an incidence of 30% or more, are: dry mouth, vomiting, constipation, flushing and nasal congestion.
The 4 RCTs included in this evidence summary do not provide evidence for the efficacy or safety of long-term oral glycopyrronium bromide use. Larger RCTs are needed to further evaluate oral preparations of glycopyrronium bromide for treating hypersalivation in adults, children and young people.
About this evidence summary
'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.
The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.
The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.