Advice

Key points

Key points

The content of this evidence summary was up-to-date in February 2017. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.

Regulatory status: new medicine. Glycopyrronium bromide (Sialanar) is an antimuscarinic (anticholinergic) medicine licensed in September 2016 for the symptomatic treatment of severe sialorrhoea (chronic pathological drooling) in children and adolescents aged 3 years and older with chronic neurological disorders. Sialanar is licensed for short-term intermittent use and is only licensed in children. There is limited clinical trial evidence on the use of glycopyrronium in adults with sialorrhoea. Sialanar 320 micrograms/ml oral solution is the first formulation of glycopyrronium bromide licensed for this indication in the UK.

Overview

This evidence summary discusses 2 small randomised controlled trials (RCTs) that compared glycopyrronium bromide with placebo for the treatment of severe sialorrhoea in children and young people with chronic neurological conditions. The majority of participants had cerebral palsy.

In both RCTs, participants treated with glycopyrronium bromide had statistically significantly improved drooling after 8 weeks, (measured using the modified Teacher's Drooling Scale [mTDS]), compared with placebo.

Adverse effects were common with glycopyrronium bromide, mostly due to its anticholinergic action. The most commonly reported adverse effects include dry mouth, constipation, urinary retention, reduced bronchial secretions and flushing. The SPC advises that glycopyrronium bromide can cause thickening of secretions, which may increase the risk of respiratory infection and pneumonia. Glycopyrronium bromide should be used with caution in people with heart problems due to its potential increase in heart rate, blood pressure and rhythm disorders (SPC: glycopyrronium).

There is a lack of long-term safety data for glycopyrronium bromide, and the SPC recommends that the total treatment duration should be kept as short as possible.

It is not possible to determine the relative effectiveness of glycopyrronium bromide compared with other treatments for severe sialorrhoea because glycopyrronium has only been compared to placebo. Because Sialanar is not bioequivalent to other formulations of glycopyrronium bromide, switching to Sialanar should only be conducted under supervision to ensure that efficacy and side effects are balanced. The effectiveness of glycopyrronium bromide should be balanced against the adverse effects associated with treatment.

A summary to inform local decision-making is shown in table 1.

Table 1 Summary of the evidence on effectiveness, safety, patient factors and resource implications

Effectiveness

  • After 8 weeks treatment, oral glycopyrronium bromide significantly improved drooling, measured using the mTDS, in children and young people with neurological conditions, compared with placebo (2 RCTs, n=77).

  • One RCT had a high drop-out rate (12/39, 31%), and children who did not complete the study were not included in the efficacy analysis, which may have introduced bias (Mier et al. 2000).

Safety

  • The SPC states that adverse effects are common with glycopyrronium bromide due to its anticholinergic action. The most common adverse reactions include dry mouth, constipation, diarrhoea, vomiting, urinary retention, flushing and nasal congestion.

  • The SPC advises that anticholinergic adverse effects may be dose dependent and difficult to assess in a child with disabilities. Treatment should be stopped in the event of constipation, urinary retention or pneumonia.

  • Due to the lack of long term safety data, glycopyrronium bromide is recommended for short‑term intermittent use only.

Patient factors

  • Glycopyrronium bromide was associated with more adverse effects and discontinuations because of adverse effects than placebo.

  • The SPC recommends that glycopyrronium bromide should be taken at least one hour before or at least two hours after meals or at consistent times with respect to food intake.

  • Most children in the clinical trials had cerebral palsy. Glycopyrronium has not been extensively tested in children with other neurological conditions.

Resource implications

  • Glycopyrronium bromide 400 microgram/ml oral solution (Sialanar) costs £320 per 250 ml bottle (MIMS, February 2017). At a dose of 1,600 micrograms (4 ml) three times daily the 28-day cost is £430.08 (based on a child weighing 33 kg at a dose of 48 micrograms/kg glycopyrronium bromide).

  • Once opened the bottle has a shelf life of 28 days. Any liquid remaining after this time should be discarded.

  • The manufacturer estimates that there are approximately 1,500 children in England who may be eligible for treatment with glycopyrronium bromide.