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Transdermal scopolamine and glycopyrrolate for sialorrhea and salivary fistula

last modified on: Tue, 12/28/2021 - 08:38

return to: Hypersalivation Ptyalism Sialorrhea

Botulinum toxin treatment of sialorrhea was formerly considered 'third-line treatment' in use of pharmacotherapy for sialorrhea (Tszeng 2002) with a combination of approaches to include positioning techniques and behavior therapy in that these 'alternatives are often used in combination, as single -approach therapy is often unsuccessful' (Tszeng 2002 citing Blasco 1996).

Merello et al identified in 2008 that "that the management of sialorrhea in PD [Parkinsons disease], it is proposed that glycopyrrolate should be evaluated before considering botulinum toxin injections" (Merello 2008).  

More recent work (Sridharan 2018) supports use of  botulinum toxin (Btx) in favor glycopyrrolate through a meta-analysis comparing placebo, benztropine, botulinum toxins A and B to identify 'only botulinum toxins A and B were associated with significant therapeutic effects in Parkinson's disease".  These investigators identified through this comparative meta-analysis that 'Benztropine and  botulinum toxins A and B were considered to be effective in reducing sialorrhea associated with neurological disorders".

A more recent publication identified Botulinum neurotoxin (BoNT) to be 'first line of pharmacotherapy for chronic sialorrhea' (Jost 2019)

Drug Information: Scopolamine is an alkaloid that inhibits the muscarinic receptors for acetylcholine. It produces both peripheral anti-muscarinic properties and central sedative, antiemetic and amnestic effects. Limited bioavailability when administered orally - used through transdermal delivery

1.5 mg drug reservoir with a priming does (140 microg ) to reach steady concentration quickly; the patch releases 0.5 mg alkaloid over a period of 3 days (release rate of 5 microg/h) (Renner UD 2005)

TTS-S = Transdermal therapeutic system for scopolamine

 

Uses of scopolamine:

  1. Premedication before anesthesia for antiemetic effect
  2. "the most effective single agent to prevent motion sickness" 
  3. Considered by some as an initial treatment for sialorrhea (Squires 2012)
    1. Administered to 30 young disabled patients with various diagnoses including cerebral palsy - with significant reduction in saliva reported at one week, but 4 dropped out of treatment due to side effects (Mato 2010)
    2. Benefit may be short-lived as the body becomes accustomed to the drug or as side effects become intolerable

Adverse effects of scopolamine

  1. Hallucinations  (toxic psychosis mainly in elderly and paediatric patients) - reported 'only occasionally (Nachum 2006)
  2. Vertigo
  3. Dry mouth
  4. Drowsiness (TTS-S have the incidence of drowsiness reported with oral dimenhydrinate (Nachum 2006)
  5. Difficulty urinating
  6. Rash
  7. Headache
  8. Blurred vision

Alternative Medical Therapy 

  1. Glycopyrrolate   (Arbouw 2010)- reported oral glycopyrrolate 1 mg orally (po) tid 'effective and safe' in reducing drooling in 23 patients with Parkinsons
    1. Advantage of not crossing the blood-brain barrier- hence minimal central side effects (advantage in those with cognitive decline) 
    2. "In a recent review of the management of sialorrhea in PD, it is proposed that glycopyrrolate should be evaluated before considering botulinum toxin injections (Merello 2008)
  2. Amitryptilene
  3. Sublingual atropine drops
  4. Benztropine 
  5. Radiotherapy

 

 

References

  1. Renner UD, Oertel R, Krich W: Pharmacokinetics and pharmacodynamics of clinical use of scopolamine. Ther Drug Monit 2005 Oct;27(5):655-65 
  2. Nachum Z, Shupak A, and Gordon CR: Transdermal scopolamine for prevention of motion sickness: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 2006;45(6):543-66
  3. Banfi P, Ticozzi N, Lax A, Guidugli GA, Nicolini A and Silani V: A review of options for treating sialorrhea in amyotrophic lateral sclerosis. Respir Care 2015 Mar;60(3):446-54
  4. Squires N, Wills A, and Rowson J: The management of Drooling in adults with neurological conditions  Current Opinion in Otolaryngology & Head and Neck Surgery Olv 20(3), June 2012, p 171-176
  5. Mato A, Limeres J, Tomas I et al Management of drooling in disabled pateints with scopolamine patches. Br J Clin Pharmacol 2010;69:684-688
  6. Arbouw M, Movig K, Koopmann M et al Glycopyrrolate for sialorrhea in Parkinson Disease. A randomized double-blind, crossover trial. Neurology 2010;74:1203-1207.
  7. Merello M: Sialorrhoea and drooling in patients with Parkinson's disease: epidemiology and management. Drugs Aging 2008;25:1007-1019
  8. Jost WH1, Bäumer T2, Laskawi R3, Slawek J4, Spittau B5, Steffen A6, Winterholler M7, Bavikatte G8.Therapy of Sialorrhea with Botulinum Neurotoxin.Neurol Ther. 2019 Sep 21. doi: 10.1007/s40120-019-00155-6. [Epub ahead of print]
  9. Sridharan K1, Sivaramakrishnan G2.Pharmacological interventions for treating sialorrhea associated with neurological disorders: A mixed treatment network meta-analysis of randomized controlled trials.J Clin Neurosci. 2018 May;51:12-17. doi: 10.1016/j.jocn.2018.02.011. Epub 2018 Feb 21.
  10. Tscheng DZ1.Sialorrhea - therapeutic drug options.Ann Pharmacother. 2002 Nov;36(11):1785-90.
  11. Blasco PA, Stansbury JCK. Glycopyrrolate treatment of chronic drooling. Arch Pediatr Adolesc Med 1996;150:932-5.
  12. Schwalje AT and Hoffman HT.  Intraductal Salivary Gland Infusion With Botulinum Toxin. Laryngoscope Investigative Otolaryngology pp 520-525 accessed on line Oct 19 2019:  https://onlinelibrary.wiley.com/doi/pdf/10.1002/lio2.306