Advice
Product overview
Mode of action
Glycopyrronium bromide is an antimuscarinic (anticholinergic) medicine that reduces salivary secretions. It has limited ability to penetrate the blood brain barrier, although the extent of penetration is unknown (SPC: glycopyrronium).
Regulatory status
Glycopyrronium bromide (Sialanar) received a European marketing authorisation in September 2016 and was launched in the UK in January 2017. Each millilitre (ml) of Sialanar 320 micrograms/ml oral solution contains 400 micrograms glycopyrronium bromide. Glycopyrronium bromide 400 microgram/ml oral solution is licensed for the symptomatic treatment of severe sialorrhoea (chronic pathological drooling) in children and adolescents aged 3 years and older with chronic neurological disorders (SPC: glycopyrronium).
Although glycopyrronium bromide is used in clinical practice, Sialanar is the first preparation licensed for this indication in the UK. Previously, people requiring treatment with glycopyrronium bromide have used imported products (including the US product Cuvposa) or formulations made by specials manufacturers. The different formulations of glycopyrronium bromide are not bioequivalent (see dosing information).
Dosing information
The SPC states that each millilitre (ml) of oral solution contains 400 micrograms of glycopyrronium bromide, equivalent to 320 micrograms of glycopyrronium. Care should be taken when calculating the dose of Sialanar, with particular attention to whether the dose is expressed as glycopyrronium or glycopyrronium bromide. The dosing schedule is based on the weight of the child, starting with approximately 12.8 micrograms/kg glycopyrronium per dose (equivalent to 16 micrograms/kg of glycopyrronium bromide per dose) three times daily and increasing the dose every 7 days using the dosing table (see table 1 in the SPC).
Dose titrations should be carried out in discussion with the parent or carer to assess both efficacy and adverse effects until an acceptable maintenance dose is achieved. The maximum single dose is 64 micrograms/kg body weight of glycopyrronium or 6 ml (1,900 micrograms glycopyrronium, equivalent to 2,400 micrograms glycopyrronium bromide) three times daily, whichever dose is less (SPC: glycopyrronium).
Food reduces the absorption of glycopyrronium bromide, and the SPC advises that it should be taken at least 1 hour before food or at least 2 hours after meals, or at consistent times with respect to food intake. Specialists involved in developing this evidence summary advised that this dosing regimen may be challenging in children requiring assisted feeding or in those with a gastrostomy, and particular care should be taken when determining the most effective dosing regimen for these children.
In children and young people with mild to moderate renal impairment (eGFR 30–90 ml/min/1.73m2) the dose should be reduced by 30% (see dosing table 2 in the SPC).
The EPAR for Sialanar reports on a bioavailability study conducted by the manufacturer in healthy adults. It found that Sialanar is approximately 25% more bioavailable compared with Cuvposa, the glycopyrronium bromide formulation licensed in the US and used in 2 studies by Zeller et al (2012a and 2012b). Because of the difference in bioavailability the dose of Sialanar is approximately 20% lower than the recommended dose of the Cuvposa.
Cost
The company has advised that Sialanar costs £320.00 for a 250 ml bottle (MIMS, February 2017). The manufacturer estimates that the average dosage of glycopyrronium bromide is likely to be 1,600 microgram (4 ml) three times daily. This equates to a 28-day cost of £430.08.
Once opened a bottle of Sialanar has a shelf life of 28 days. Any liquid remaining after this time should be discarded.