Intervention and alternatives

Intervention and alternatives

Glycopyrronium bromide is an antimuscarinic agent that reduces salivary secretions and does not cross the blood–brain barrier. No oral preparations (tablets and solution or suspension) of glycopyrronium bromide are licensed in the UK. Therefore, the use of imported oral preparations or those prepared by 'specials' manufacturers for treating hypersalivation in adults, children and young people is unlicensed.

Glycopyrrolate (glycopyrronium bromide) tablets 1 mg and 2 mg are available in the USA, licensed for adjunctive therapy in treating peptic ulcer. Glycopyrrolate (glycopyrronium bromide) 1 mg/5 ml oral solution (Cuvposa) was licensed in the USA in 2010 to reduce chronic severe drooling in children and young people aged 3–16 years with a neurological condition associated with problem drooling, such as cerebral palsy.

The recommended dosage is 0.02 mg/kg 3 times daily initially, with doses titrated in increments of 0.02 mg/kg every 5–7 days based on therapeutic response and adverse effects. The maximum recommended dose is 0.1 mg/kg 3 times daily (not to exceed 1.5 to 3 mg per dose based on weight). Doses should be given at least 1 hour before, or 2 hours after, meals.

Glycopyrronium bromide is licensed in the UK as an injection for preoperative and intraoperative use, as a powder for solution for iontophoretic treatment (electromotive drug administration) of hyperhidrosis (excessive sweating), and for use in a single-dose dry-powder inhaler for chronic obstructive pulmonary disease.

Condition

Hypersalivation (sialorrhoea) is the excessive production of saliva. This presents as drooling in children, young people and adults with a neurological condition, such as cerebral palsy or Parkinson's disease. Hypersalivation can also be an adverse effect of drug treatment (for example, clozapine).

Chronic drooling can be defined as the unintentional loss of saliva from the mouth. Zeller et al. (2012a) reported that although drooling is normal in infants, it usually stops by 15–18 months of age, and is considered pathological if present after 4 years. Drooling can result in perioral chapping, irritation, maceration and secondary infection of the skin. The prevalence of moderate-to-severe drooling in children, young people and adults with neurological conditions, particularly cerebral palsy, is estimated to be between 10% and 37% (Zeller et al. 2012a and Mier et al. 2000 ).

The full NICE clinical guideline on Parkinson's disease states that excessive saliva or drooling occurs in 70–80% of people with Parkinson's disease and may be more common in men. Drooling is thought to result from oropharyngeal dysfunction, including reduced swallowing frequency.

Bird et al. (2011) reported that, second to sedation, hypersalivation is one of the most common adverse effects attributed to clozapine, occurring in 30–80% of people taking the drug.

Alternative treatment options

A review of the management of drooling in adults with neurological conditions (Squires et al. 2012) stated that management is best accomplished using a multidisciplinary team approach. Initial management is conservative (mostly behavioural) if symptoms are mild and infrequent. When conservative management is no longer adequate, drug treatment (usually with an antimuscarinic agent) is considered. Similar approaches have been tried in children and young people with neurological conditions (Mier et al. 2000, Walshe et al. 2012 and Zeller et al. 2012a).

Drug treatments other than glycopyrronium bromide that have been used to manage hypersalivation include the following (UKMI, Medicines Q&A, 2012):

  • antimuscarinic drugs (amitriptyline, atropine, benzatropine, trihexyphenidyl hydrochloride, hyoscine hydrobromide)

  • beta-blockers.

  • botulinum toxin.

None of these are licensed in the UK for treating hypersalivation.

The full NICE clinical guideline on Parkinson's disease states that management of sialorrhoea or drooling may include:

  • referral to a speech and language therapist for assessment of swallowing ability

  • behavioural management techniques to encourage regular saliva swallows

  • use of a portable metronomic brooch as a reminder for saliva swallows

  • lip seal and swallow exercises

  • sublingual 1% atropine ophthalmic solution twice daily

  • injection of salivary glands with botulinum toxin A.

Current strategies for clozapine-induced hypersalivation include topical and oral antimuscarinic drugs, alpha-adrenergic drugs (for example, clonidine), botulinum toxin and substitute benzamide derivatives (such as amisulpride) (Bird et al. 2011 ).