Severe sialorrhoea (drooling) in children and young people with chronic neurological disorders: oral glycopyrronium bromide

Other treatments

Other medicines that have been used to manage sialorrhoea include the following (Specialist Pharmacy Service, 2015):

None of these medicines are licensed in the UK for managing sialorrhoea and their use would be off-label.

Costs of other treatments

See table 3 for the costs of other treatments in comparison to Sialanar.

Table 3 Costs of other treatments

Current or estimated usage

Proveca, the manufacturer of glycopyrronium bromide (Sialanar) estimates that there are approximately 18,595 children in England with cerebral palsy, of whom 15% (2,789 children) are estimated to have severe sialorrhoea. The manufacturer estimates that about 55% of these children will be eligible for treatment, giving a potential treated population of 1,534 children.

Likely place in therapy

The NICE guideline on cerebral palsy in under 25s recommends considering anticholinergic medication to reduce the severity and frequency of drooling in children and young people with cerebral palsy. The guideline recommends glycopyrronium bromide (oral or by enteral tube), transdermal hyoscine hydrobromide or trihexyphenidyl hydrochloride (for children with dyskinetic cerebral palsy, but only with input from specialist services).

The results of the 2 RCTs in this evidence summary involving a total of 77 children and young people with neurological conditions and severe sialorrhoea found after 8 weeks treatment glycopyrronium bromide reduced drooling (measured using the modified Teacher's Drooling Scale [mTDS]) compared with placebo. There are no studies supporting the chronic use of glycopyrronium bromide for this indication, and the maximum duration of treatment is 24 weeks (EPAR: glycopyrronium). Adverse effects are more common in people treated with glycopyrronium bromide compared with placebo. Many adverse effects are due to glycopyrronium bromide's anticholinergic action, which include dry mouth, constipation, diarrhoea and urinary retention. Anticholinergic effects are common with glycopyrronium bromide, may be dose dependent and difficult to assessment in a disabled child (SPC: glycopyrronium).

The majority of participants in the 2 RCTs had cerebral palsy, it is not known if the efficacy and safety results observed in these people will be the same in children with other neurological conditions. Although some participants in the 2 RCTs had previously received medicines to treat sialorrhoea, including glycopyrronium bromide, details of the treatments are not provided. It is not known whether glycopyrronium bromide is an effective treatment for people who have failed to respond to other treatments.

Glycopyrronium bromide oral solution is the first and only medicine licensed in the UK 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 only licensed in children, there is limited clinical trial evidence on the use of glycopyrronium in adults with sialorrhoea. Although glycopyrronium bromide has been used in the UK for many years for this indication, this has been through the use of unlicensed products or preparations made by specials manufacturers. The General Medicine Council's good practice guidelines recommends that prescribers should usually prescribe medicines in accordance with the terms of their license, and that the use of unlicensed medicines should generally be limited to when there is no suitable licensed medicine.

Despite glycopyrronium bromide being used for many years in the UK, the EPAR highlights that it has been primarily used in adults, in both acute and chronic settings and in formulations than Sialanar. The adverse effect profile established in other populations cannot be applied to children with chronic neurological disorders, many of whom have multimorbidity. In addition, each formulation of glycopyrronium bromide has its own bioavailability profile. Sialanar is not bioequivalent to other formulations of glycopyrronium bromide and switching to Sialanar should only be conducted under supervision to ensure that efficacy and side effects are balanced.

The 2 RCTs measured patient-oriented primary outcomes that reported on improvements in drooling, although neither study measured quality of life. The EPAR summarises the results of a mapping exercise that estimated the effect of drooling on quality of life in people with cerebral palsy. The EPAR concluded that quality of life was clearly affected in children with cerebral palsy who had a drooling problem, compared with children who did not drool.

It is not possible to determine the relative effectiveness of glycopyrronium bromide compared with other treatments for severe sialorrhoea because glycopyrronium bromide has only been compared to placebo in all published RCTs. In Zeller et al. (2012a) participants treated with glycopyrronium bromide had a mean mTDS score of approximately 7 at baseline (severe symptoms- drools to the extent that clothing becomes damp; frequently), which improved after 8 weeks treatment to a score of approximately 3 (mild symptoms- only the lips are wet; frequently). The effectiveness of glycopyrronium bromide should be balanced against the adverse effects associated with the treatment (EPAR: glycopyrronium).