A link to a publication on the BUDGET IMPACT ANALYSIS OF ORAL GLYCOPYRRONIUM BROMIDE (SIALANAR™)  FOR THE SYMPTOMATIC TREATMENT OF SEVERE SIALORRHOEA (DROOLING) IN THE UK SETTING:  can be found here

Sialanar

Sialanar received a European Paediatric Use Marketing Authorisation (PUMA) on 15th 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

Glycopyrronium bromide already has an accepted place in the treatment armamentarium for the management of sialorrhoea, appearing as a treatment option in all UK treatment guidelines published to date and several national formularies recommend the use of glycopyrronium bromide for the management of sialorrhoea including UK, Germany and NL.

The benefit of glycopyrronium in alleviating pathological drooling in children with neurological disorders has been demonstrated in two randomised, placebo-controlled clinical trials (Zeller, 2012a study and Mier, 2000). Both had an 8 week treatment duration. The pivotal 8-week study, Zeller at al. 2012a, conducted with thirty-eight patients demonstrated superiority of glycopyrronium bromide over placebo in reduction of drooling in children 3-16 years old. The initial dose was 0.02 mg/kg, which was increased in 0.02 m g/kg increments every 5 to 7 days up to a maximum dose of 0.1 mg/kg (but not to exceed a maximum dose of 3 mg t.i.d, regardless of weight). The responder rate at Week 8, ≥ 3 point improvement on the modified Teacher's Drooling Scale (mTDS) was significantly higher for glycopyrronium (14/19; 73.7%) than for placebo (3/17; 17.6%) (p = 0.0011), with improvements starting 2 weeks after treatment initiation (52.6% vs. 0%; p=0.00007). The favourable effects of glycopyrronium on the mTDS were corroborated by results of investigator and patient/caregiver rated global assessments.

The study by Mier et al. conducted in thirty-nine children aged 4 years and older with neurodevelopmental conditions and severe sialorrhoea demonstrated superiority of glycopyrronium over placebo. Doses were increased in 0.6 mg increments in both groups but from different starting doses: 0.6 to 2.4 mg in the lower weight group and 1.2 to 3.0 mg in the higher weight group. Drooling score on the mTDS improved in a linear manner with increasing dose level over the 4-week titration period; scores were 6.0 at dose level 1, 4.5 at level 2, 3.6 at level 3, and 2.6 at level 4. After an additional 4 weeks at the highest individual dose the mean drooling score had decreased further to 2.3.

These two randomised, double-blind studies are supported by a long-term safety study by Zeller at al. 2012b. In this 24-week, open-label study glycopyrronium was administered to 137 paediatric patients between 3-18 years of age. At Week 24, 52.3% (95% CI 43.7–60.9) of subjects were responders (≥ 3 point reduction on the mTDS). The proportion of responders ranged between 40.3% and 56.7% over the 6 assessment points during the 24 week study period.

References

Mier RJ, Bachrach SJ, Lakin RC, et al. Treatment of sialorrhea with glycopyrrolate: A double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000;154:1214-8.

Zeller RS, Lee H-M, Cavanaugh PF, Davidson J. Randomized phase III evaluation of the efficacy and safety of a novel glycopyrrolate oral solution for the management of chronic severe drooling in children with cerebral palsy or other neurologic conditions. Ther Clin Risk Manag 2012a;8:15-23.

Zeller RS, Davidson J, Lee H-M, Cavanaugh PF. Safety and efficacy of glycopyrrolate oral solution for management of pathologic drooling in pediatric patients with cerebral palsy or other neurologic conditions. Ther Clin Risk Manag 2012b; 8:25-32.