Download Hypersalivation can hyoscine hydrobromide be used to treat it?

Medicines Q&As
Q&A 51.6
Hypersalivation – can hyoscine hydrobromide be used to treat it?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 25th June 2015
Background
A general description of the pharmacological approach to the management of non drug-induced
hypersalivation is contained in a separate Q&A document: No 50: Hypersalivation – what drug
treatment options are available?
In the UK, hyoscine hydrobromide (also called scopolamine hydrobromide) is available as an
injection, tablets (e.g. Kwells), chewable tablets (e.g. Joy-rides) and as a transdermal patch
(Scopoderm). None of these products are licensed to treat hypersalivation.
There are no published studies on the use of hyoscine butylbromide (Buscopan) for the management
of non drug-induced hypersalivation. It would not be expected to be effective by mouth as its
absorption from the gastrointestinal tract is very poor.
Answer
Oral and subcutaneous route
There are no published studies available on the use of oral or subcutaneous hyoscine hydrobromide in
the management of hypersalivation. Anecdotally, this has tended to be a treatment option with a usual
starting dose of 200 – 400 micrograms two or three times daily orally or subcutaneously. Hyoscine
hydrobromide tablets are available over-the-counter (for the prevention of motion sickness).
Transdermal patches
Scopoderm (hyoscine) patches are licensed for the prevention of travel sickness symptoms e.g.
nausea, vomiting and vertigo, in adults and children aged 10 years or over. Each patch contains
1.5mg hyoscine U.S.P. and the average amount of hyoscine absorbed from each patch in 72 hours is
1mg (1). The patch should be applied to the hairless skin behind the ear. Steady state plasma levels
of hyoscine are reached within about 6 hours of application of the patch and are maintained for up to
72 hours if the patch is not removed. The patch must be removed every 3 days, and replaced with a
fresh patch behind the other ear (1).
Transdermal hyoscine patches offer several advantages over other treatments including ease of
administration, maintenance of steady state concentrations and a low incidence of systemic side
effects compared with other anticholinergics (2). Peak concentration side effects such as those seen
with pulse entry of the drug are minimised (3).
Transdermal hyoscine has been investigated for the treatment of hypersalivation (2-11) and it is
assumed that all studies described below utilised a 1.5mg patch similar to that available in the UK, but
this is not always stated.
Randomised controlled studies
A prospective randomised double-blind crossover placebo-controlled trial has been conducted to
evaluate the efficacy of transdermal hyoscine in 30 disabled patients (aged 12-58 years) with persistent
drooling (4). After a baseline period, patients applied either a hyoscine 1.5mg or a placebo patch every 72
hours for 2 weeks with a 1-week washout period before crossover. Four patients withdrew from the study
due to hyoscine side-effects (irritability (n=1), agitation (n=1), skin reaction (n=2)). One case each of
urinary retention, mydriasis and skin reaction also occurred. At baseline, 79% of all the patients had
grade 3 drooling (severe/fulsome) and 21% had grade 2 (mild/moderate). At the end of the second
weeks’ of treatment, 19% of hyoscine treated patients had grade 3 drooling, 62% had grade 2 and 19%
had grade 1 (dry) (p<0.001 vs. baseline). Frequency of drooling was also significantly reduced from 6
bibs/day to 3 bibs/day following two weeks of hyoscine treatment (p<0.005).
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In another double-blind placebo-controlled crossover study, 11 developmentally delayed children with
moderate to severe drooling (aged over 5 years and weighing more than 15kg) were randomly assigned
to two weeks treatment with transdermal hyoscine or a placebo patch, with a one-week ‘wash-out’ period
before treatment crossover (5). The patches were applied to the children’s backs to avoid tampering,
covered by porous opaque gauze and changed twice weekly. There was less drooling on 80% of days
during active treatment compared to 19% during the placebo period. Over half of the patients had a
statistically significant reduction in drooling, and 31% had cessation of drooling, while wearing the
hyoscine patch. One child withdrew because of extreme dizziness and falling while wearing the placebo
patch. Reported side effects included pruritus around the site of the patch (3 patients) and increased
mouthing behaviours (3 patients) although it is not clear whether this occurred during the active or
placebo phase. One child with a pre-existing seizure disorder had a cluster of simple partial seizures
during the active-patch phase. It was noted by the clinicians that two-thirds of the patients had pupillary
dilatation whilst wearing the active patch. Four patients continued to use patches successfully for 3
months after study end.
Controlled studies
In a double-blind placebo-controlled crossover study of 15 adult patients with special needs, the response
to 3 days of treatment with transdermally applied hyoscine was described as: "excellent in four patients
(no drooling), good in seven, moderate in two and two patients did not respond" (3). In this study mild
objective signs of adverse effects were reported in 11 patients, which were relatively similar in type,
frequency and degree in the active drug and placebo periods. Fifteen adverse effects were reported.
Mouth dryness, tiredness, conjunctival irritation and thirst were equally reported in both 3 day periods.
Behavioural changes were reported in three patients, positive effects with the active drug treatment in two
and restlessness with placebo treatment in one. During the hyoscine treatment period, one patient
reported loss of appetite and one reported increased swallowing difficulties.
Non-comparative studies
A short-term non-comparative study from 1990 divided 109 adult patients into 7 clinical groups
depending on the likely cause of hypersalivation, and offered treatment with hyoscine patches for up
to 7 days (6). The investigators concluded that 43-100% of patients in the 7 groups experienced
"noticeable to excellent" improvement, although no objective measurements were taken. Those with
tracheotomies and peritonsillar abscess fared less well than other groups (aerodigestive tumours,
neurological cause, parotidectomy, tonsillitis/pharyngitis). Three patients experienced urinary
retention, which may have been attributed to hyoscine, and resulted in treatment discontinuation.
Seven patients suffered from blurred vision, but only one discontinued treatment on account of this
effect. Nearly half of the 22 patients with tonsillitis and pharyngitis discontinued treatment after 24
hours due to dry mouth. Three patients applied two patches simultaneously for up to 7 days with no
apparent increase in side effects.
Case reports
One case report describes the effective control of drooling using transdermal hyoscine patches in a
traumatic brain-injured adult patient (2). Saliva flow decreased by an average of 30% with one patch
(applied for 3 days) and by 59% with two-patch dosing (applied every 3 days and used for over 4
months). No significant side effects were observed. The authors stress that the efficacy and potential
side effects of transdermal hyoscine are subject to individual variation but that more than one patch may
be effective if a further reduction in salivary flow is required and there are no contra-indications.
There is also a report of an 80-year-old patient with peritoneal carcinomatosis who was successfully
treated with transdermal hyoscine (20 micrograms/hour) to reduce hypersalivation and to control nausea
and vomiting due to bowel subocclusion (7). Modest side effects were reported and the treatment was
continued until the patient died 2 months later.
In two patients with severe dysphagia following a stroke, transdermal scopolamine (1.0mg/2.5cm2 every
72 hours) “probably reduced salivation” (8). One patient experienced worsening of urinary retention.
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One case report describes the development of strabismus in a 4-year old child treated with a hyoscine
patch for drooling. A quarter of a 1.5mg hyoscine patch was affixed to the skin behind his ear to release
a dose of 150 micrograms of hyoscine at a constant rate over 3 days. In five days a strabismus
developed, which resolved approximately seven days after removal of the patch (11).
The side effects of hyoscine patches are described in the SPC (1). Note, that there has been a report of
toxic psychosis with the use of hyoscine patches (12), and whilst other cases of acute psychosis and
confusion have been reported, such complications probably occur in less than 1 in 50 000 cases (13).
There have also been two reports of unilateral mydriasis (14), in one case this occurred when a user
inadvertently transferred hyoscine from the patch to the eye by rubbing her eyes after applying the patch.
A further case report describes two children with disabilities who showed reduced near vision and dilated
pupils with reduced or no response to light, which improved on removal of the hyoscine patch. The
authors comment that as the effect of the drug may be cumulative, and many patients are unable to
communicate difficulties, clinicians need to be aware of these possible side effects (15). A retrospective
case series of 5 children (age range 8-18 years) who regularly wore hyoscine patches to control drooling
found that the anticholinergic effects of the drug can cause photophobia and impair vision due to pupil
dilatation and paralysis of accommodation. The authors recommend that patients using hyoscine patches
in this way should have visual assessments and appropriate spectacles prescribed if necessary (16).
There is little information available on the long-term use of hyoscine patches. One patient is documented
as using the preparation continuously for 24 days on his own initiative, but no further details are given (6).
Another used two patches at the same time for over 4 months (2). In addition, a two-year-old child with
cerebral palsy was successfully treated with transdermal hyoscine patches (one 1.5mg patch every 72
hours) to manage excessive drooling for 2 years. No significant side effects were observed although
cognitive side effects could not be assessed because of his limited cognitive function (9). More recently,
the case of a 24-year old male patient with cerebral palsy and pyschomotor retardation has been
described. A significant reduction in the severity of drooling was reported within 24 hours of treatment
with a transdermal hyoscine patch (one 1.5mg patch every 72 hours), which was maintained for 3 years.
Mild oliguria was reported, but this did not necessitate discontinuation of treatment (10).
Long-term use risks the sequelae of dry mouth such as increased dental decay, mouth infections,
swallowing and speech difficulties. It is also not known whether long-term use will facilitate tolerance,
requiring an increase in dosage. One case of withdrawal symptoms following the cessation of 10
days’ use of transdermal hyosine patches for motion sickness has been reported, with symptoms
resolving after 3 days (17). Clinicians should be aware of all these potential problems and monitor for
them if chronic use is deemed necessary. However, short-term use may be acceptable for many
patients, e.g. post-ENT surgery, or for special occasions in those with chronic hypersalivation where
drooling may be socially embarrassing.
Nebulized route
One author describes three case reports of the administration of hyoscine hydrobromide via a portable
nebulizer at a dose of 800 micrograms two or three times daily. The three patients felt a beneficial effect
within 30 minutes and had no troublesome systemic side effects, and the author suggests that hyoscine
hydrobromide may have a local action on the salivary glands. The patients found nebulized hyoscine to
be more effective than transdermal hyoscine (18).
Two further case reports have been described. One patient with hypersalivation, who had previously
been treated unsuccessfully with oral propantheline, initially received nebulized hyoscine
800 micrograms three times a day, with a noticeable improvement within 24 hours. However, the
patient was concerned about dryness of her mouth immediately following nebulizations and a change
in taste sensation. Following several dose adjustments, a dose of 200 micrograms four times a day
provided significant improvement and was well tolerated, although fluctuations in her oral salivation
remained. The second patient reported a dramatic reduction in oral secretions following seven days
treatment with nebulised hyoscine 400 micrograms four times a day (19).
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Medicines Q&As
Summary


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None of the hyoscine hydrobromide preparations currently available in the UK are licensed to
treat hypersalivation.
Although there are no published studies, oral or subcutaneous hyoscine hydrobromide has
been used anecdotally for the management of hypersalivation.
Three small, short-term studies have reported successful use of transdermal hyoscine
patches for the management of hypersalivation in adults and children (3,4,5). Transdermal
hyoscine patches offer several advantages over other treatments including ease of
administration, maintenance of steady state concentrations and a low incidence of systemic
side effects compared with other anticholinergics (2). Most patients were treated with one
patch at a time changed every 3 days (on the whole), but two patches have been used
successfully in a minority.
Hyoscine patches may be particularly useful for patients with intractable swallowing difficulties
(e.g. head and neck cancers) who may have problems with drooling or choking owing to the
normal production of saliva.
Five cases of successful use of nebulized hyoscine hydrobromide have been described (18,19).
Data on long-term efficacy and safety of hyoscine by any route are exceedingly sparse.
Limitations
 There are no major randomised placebo-controlled trials for any drug to treat hypersalivation, so
the amount of published evidence is limited. No randomised double-blind comparative studies
are available. The evidence for the use of some of these drugs is limited to anecdotal reports
only.
 The majority of the studies are short-term so long-term efficacy and safety data are not available.
 Most of the studies included small numbers of patients.
 The majority of the studies rely on subjective outcome measurements since it is difficult to
assess saliva production objectively particularly as there is inter-individual variation in saliva
production. No single method of measurement of salivary flow and outcome presentation is
available.
 This Q&A has not addressed the management of drug-induced sialorrhoea.
References
(1) SPC Scopoderm 1.5mg patch. Novartis Consumer Health. Accessed via
http://www.medicines.org.uk/emc/ on 20th July 2015. SPC last updated on the eMC 23rd July
2014.
(2) Dreyfuss P, Vogel D, Walsh N. The use of transdermal scopolamine to control drooling: a case
report. Am J Phys Med Rehabil 1991;70:220-222.
(3) Brodtkorb E, Wyzocka-Bakowska MM, Lillevold PE et al. Transdermal scopolamine in drooling.
Journal of Mental Deficiency Research 1988;32:233-237.
(4) Mato A, Limeres J, Tomas I et al. Management of drooling in disabled patients with scopolamine
patches. Br J Clin Pharmacol 2010;69:684-688.
(5) Lewis DW, Fontana C, Mehallick LK et al. Transdermal scopolamine for reduction of drooling in
developmentally delayed children. Dev Med Child Neurol 1994;36:484-486.
(6) Talmi YP, Finkelstein Y, Zohar Y. Reduction of salivary flow with transdermal scopolamine: a
four-year experience; Otolaryngol Head Neck Surg 1990;103:615-618.
(7) Tassinari D, Poggi B, Fantini M et al. Treating sialorrhea with transdermal scopolamine.
Exploiting a side effect to treat an uncommon symptom in cancer patients. Support Care Cancer
2005;13:559-561.
(8) Rønning OM, Stavem K. Transdermal scopolamine to reduce salivation and possibly aspiration
after stroke. Journal of Stroke and Cerebrovascular Diseases 2008;17:328-329.
(9) Siegel LK, Klingbeil MA. Control of drooling with transdermal scopolamine in a child with cerebral
palsy. Dev Med Child Neurol 1991;33:1013-1014.
(10) Montero AM, Posse JL, Carmona IT et al. Control of drooling using transdermal scopolamine
skin patches. A case report. Med Oral Patol Cir Bucal 2008;13(1):E27-30.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
(11) Good WV, Crain LS. Esotropia in a child treated with a scopolamine patch for drooling. Pediatrics
1996;97:126-127.
(12) Ziskind AA. Transdermal scopolamine-induced psychosis. Postgrad Med 1988;84:73-76.
(13) Neverlien PO, Sorumshagen L, Eriksen T et al. Glycopyrrolate treatment of drooling in an adult
male patient with cerebral palsy. Clin Exp Pharmacol Physiol 2000;27:320-322.
(14) Thiele EA, Riviello JJ. Scopolamine patch-induced unilateral mydriasis. Pediatrics 1995;96:525.
(15) Firth AY, Walker K. Visual side-effects from transdermal scopolamine (hyoscine). Dev Med Child
Neurol 2006;48:137-138.
(16) Saeed M, Henderson G and Dutton GN. Hyoscine skin patches for drooling dilate pupils and
impair accommodation: spectacle correction for photophobia and blurred vision may be
warranted. Dev Med Child Neurol 2007;49:426-428.
(17) Saxena K and Saxena S. Scopolamine withdrawal syndrome. Postgrad Med 1990;87:63-66.
(18) Zeppetella G. Nebulized scopolamine in the management of oral dribbling: three case reports. J
Pain Symptom Manage 1999;17:293-295.
(19) Doyle J, Walker P, Bruera E. Nebulized scopolamine (letter). J Pain Symptom Manage
2000;19:327-328.
Quality Assurance
Prepared by
Kate Pickett, Lead Pharmacist – Formulary and Medicines Q&As, Southampton Medicines Advice
Service, University Hospital Southampton NHS Foundation Trust
Date Prepared
25th June 2015
Checked by
Nicola Watts, Lead Clinical Advice Pharmacist (based on the Q&A originally checked by Simon Wills,
Sandra Hicks and Sue Gough), Southampton Medicines Advice Service, University Hospital
Southampton NHS Foundation Trust
Date of check
5th October 2015
Search strategy:
Medline (Ovid Online): exp *SIALORRHEA/dt (limited to human and English language)
Embase (NICE Evidence): exp HYPERSALIVATION/dt (limited to human and English language and
years 1998-2015)
Drugdex (accessed via https://www.micromedexsolutions.com/)
Electronic Medicines Compendium (accessed via http://www.medicines.org.uk/emc/)
NICE Evidence Search (accessed via www.evidence.nhs.uk)
Cochrane Library (accessed via http://www.cochranelibrary.com/
NICE (accessed via http://www.nice.org.uk/)
BNF (accessed via www.medicinescomplete.com)
Available through NICE Evidence Search at www.evidence.nhs.uk
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