Advice
Overview for healthcare professionals
Overview for healthcare professionals
Regulatory status of glycopyrronium bromide
Oral glycopyrronium bromide does not have marketing authorisation in the UK for treating hyperhidrosis in children, young people or adults. Glycopyrronium bromide is available in the UK as:
-
a powder for solution licensed for iontophoretic treatment (electromotive drug administration) of idiopathic hyperhidrosis of the palms of hands and soles of feet in children and adults (Robinul powder, Amdipharm Mercury Company),
-
a 200 microgram/ml solution for injection licensed for preoperative and intraoperative use in children and adults (Amdipharm Mercury Company; Accord Healthcare), and
-
a single-dose dry-powder inhaler licensed for maintenance therapy to relieve symptoms of chronic obstructive pulmonary disease in adults (Seebri Breezhaler inhalation powder, Novartis Pharmaceuticals).
Oral preparations of glycopyrronium bromide (tablets and solution or suspension) are not licensed in the UK and must be either imported or prepared by specials manufacturers. Use of these preparations is unlicensed.
In line with the guidance from the General Medical Council (GMC), it is the responsibility of the prescriber to determine the clinical need of the patient and the suitability of using oral glycopyrronium bromide outside its authorised indications.
Evidence statements
-
No randomised controlled trials on the use of oral glycopyrronium bromide for treating hyperhidrosis were identified.
-
Five case series reporting the use of oral glycopyrronium bromide tablets were identified: 3 in a total 100 adults with focal or generalised primary hyperhidrosis; 1 in 31 children or young people with focal primary hyperhidrosis; and 1 in 19 adults or young people with compensatory hyperhidrosis after sympathectomy for focal primary hyperhidrosis.
-
Dosages of oral glycopyrronium bromide in case series ranged from 1 mg to a maximum 8 mg (in divided doses) daily, and treatment duration was variable or unreported. In all but 1 case series, participants had previously tried various treatments, and either the condition had not responded or they had been intolerant to the treatment.
-
Across the 5 case series, hyperhidrosis responded to treatment in between 67 and 90% of participants. Response rates were based on absolute responses to therapy as recorded in patient records, or on patient questionnaires, which could be subjective and do not appear to be validated.
-
Adverse effects were common, affecting between 29 and 79% of participants, the most frequent being dry mouth (affecting 16–63%). In 2 studies, around a quarter of participants stopped treatment because of adverse effects. In the study in children or young people, 1 child stopped treatment because of palpitations.
-
These case series provide weak evidence of the efficacy of oral glycopyrronium bromide for treating hyperhidrosis; the publication of well conducted randomised controlled trials would assist local decision making on this topic.
Summary of the evidence
This section gives a brief summary of the main evidence. A more thorough analysis is given in the Evidence review section.
Efficacy
No randomised controlled trials were identified that had examined oral glycopyrronium bromide for treating primary or secondary hyperhidrosis in adults, children or young people.
Five case series reporting the use of oral glycopyrronium bromide tablets in people with hyperhidrosis were identified: 3 in a mainly adult population with focal or generalised primary hyperhidrosis (Bajaj and Langtry 2007; Lee et al. 2012; Walling 2012), 1 in children or young people with focal primary hyperhidrosis (Paller et al. 2012), and 1 in adults or young people with compensatory hyperhidrosis after sympathectomy for focal primary hyperhidrosis (Gong and Kim 2013).
Dosages of oral glycopyrronium bromide ranged from 1 mg to a maximum 8 mg (in divided doses) daily, and treatment duration was variable or unreported. In all but 1 case series (Lee et al. 2012) participants had tried previous treatments for hyperhidrosis and either the condition had not responded, or they had been intolerant of the treatment.
According to patients' case notes, in Bajaj and Langtry (2007) hyperhidrosis responded to treatment with oral glycopyrronium bromide (in terms of reduced sweating) in 79% (15 out of 19) adults, and in Walling (2012) the response rate was 67% (30 out of 45). In Lee et al. (2012) the response rate was 75%, with 27 out of 36 participants showing a decrease in sweating on the Keller scale. In children and young people, Paller et al. (2012) reported that hyperhidrosis responded to treatment with oral glycopyrronium bromide in 90% (28 out of 31) of participants, based on case notes or verbal interview. In people with compensatory hyperhidrosis after sympathectomy, Gong and Kim (2013) reported a response rate of 89% (17 out of 19) on the Milanez de Campos scale, which measures everyday discomfort caused by hyperhidrosis.
Table 1 Summary of the 5 case series
|
Oral glycopyrronium bromide tablets |
Comment |
|
|
Number |
19 adults (24 adults received treatment; results reported only for 19 who attended follow-up) |
Participants had focal or generalised primary hyperhidrosis and all but 13% (3/24) had tried previous treatments |
|
Dosage and treatment duration |
2 mg twice daily increased to 2 mg 3 times daily (4 mg twice daily in 1 person; 2 mg once daily in 1 person) |
Duration of treatment not reported |
|
Effect on hyperhidrosis |
79% (15/19) respondeda; 4 stopped because of lack of efficacy |
8 out of 19 completed LASb before and after treatment: 'excellent' response in 3, 'improvement' in 4 and no improvement in 1 |
|
Adverse effects |
79% (15/19) |
Dry mouth affected 63% (12/19) |
|
Withdrawal because of adverse effects |
26% (5/19) |
Reasons: dry mouth (n=3), erectile dysfunction (n=1), headaches and urinary retention (n=1) |
|
Number |
36 adults (66 adults received treatment; results reported only for 36 who completed all follow-up) |
Participants had focal or generalised primary hyperhidrosis. None had received previous treatments |
|
Dosage and treatment duration |
1 mg twice daily increased by 2 mg daily to maximum 8 mg daily |
Duration of treatment not reported |
|
Effect on hyperhidrosis |
75% (27/36) responded on the Keller scalec |
Mean score reduction on Keller scalec from 60 to 35.9 (p<0.01) Mean score reduction on Milanez de Campos scaled from 57.9 to 38.7 (p<0.01) |
|
Adverse effects |
36% (13/36) |
Dry mouth (n=10), palpitations (n=4), headache (n=1) and 'other' (n=3). |
|
Withdrawal because of adverse effects |
None |
|
|
Number |
45 adults |
Participants had focal or generalised primary hyperhidrosis and had tried previous treatments (76% continued other treatments alongside oral glycopyrronium bromide tablets) |
|
Dosage and treatment duration |
1 mg once daily to 3 mg twice daily |
Duration of treatment not reported |
|
Effect on hyperhidrosis |
67% (30/45) respondeda,e 6 did not respond 9 withdrew because of adverse effects |
14 out of 30 people who responded reported degree of improvement as 'great', 'excellent' or '>75%' (n=6), or 'some', 'moderate' or '>50%' (n=8) |
|
Adverse effects |
Not reported |
Adverse effects are only reported for those who withdrew from treatment |
|
Withdrawal because of adverse effects |
20% (9/45) |
Dry mouth (n=4), gastrointestinal disturbance (n=2), headache (n=1), rash (n=1) and mental health effects (n=1) |
|
Number |
31 children or young people |
Participants had primary focal hyperhidrosis of the palms, soles and/or axillary area and had tried previous treatments |
|
Dosage and treatment duration |
1 mg once daily to 3 mg twice daily |
Duration of treatment ranged from 4 months to 10 years in those who found improvement |
|
Effect on hyperhidrosis |
90% (28/31) respondedf 3 did not respond |
20 rated the response as 'major' and 8 as 'adequate' |
|
Adverse effects |
29% (9/31) |
Dry mouth (n=8), dry eyes (n=3), blurred vision (n=1) and palpitations (n=1) |
|
Withdrawal because of adverse effects |
3% (1/31) |
1 stopped treatment because of palpitations |
|
Number |
19 adults or young people (age range 15 to 76 years) |
Participants had compensatory hyperhidrosis after sympathectomy for primary hyperhidrosis |
|
Dosage and treatment duration |
1 mg twice daily to 8 mg daily |
Questionnaire completed 1 month after treatment started |
|
Effect on hyperhidrosis |
89% (17/19) responded on the Milanez de Campos scale at 1 monthd |
Mean score reduced from 60.4 to 34.2 (p<0.05) |
|
Adverse effects |
42% (8/19) |
Dry mouth (n=3), palpitations (n=3), headache (n=1) and constipation (n=1) |
|
Withdrawal because of adverse effects |
None |
|
|
Abbreviations: LAS, linear analogue scale. a The degree of treatment response could not be accurately assessed from the patients' case notes, so the absolute responses were recorded. b A patient-assessed LAS (0 to 10 points) of the severity of hyperhidrosis and quality of life. An 'excellent' response was an improvement of 9 points or more, and 'improved' was an improvement of up to 8 points. c The Keller scale examines hyperhidrosis symptoms. No further details of this scale are given. d The Milanez de Campos scale examines the discomfort level of hyperhidrosis in everyday life. No further details of this scale are given. e 'Non-responders' were defined as people who reported 'no', 'slight' or 'less than 50% improvement', or stopped treatment because of lack of efficacy. f Response was based on a review of case notes or verbal interview. |
||
Safety
In case series of oral glycopyrronium bromide in people with hyperhidrosis, adverse effects have been common, the most frequent being dry mouth. In adults, Bajaj and Langtry (2007) (n=19) reported that 79% experienced adverse effects (63% dry mouth) and 26% stopped treatment because of adverse effects; in Lee et al. (2012) (n=36), 36% experienced adverse effects (28% dry mouth), though none stopped treatment as a result; and in Walling (2012) (n=45), 20% stopped treatment because of adverse effects (9% because of dry mouth). In children and young people, Paller et al. (2012) (n=31) reported adverse effects in 29% (dry mouth in 26%), and 1 child stopped treatment because of palpitations.
In people taking oral glycopyrronium bromide for compensatory hyperhidrosis after sympathectomy, Gong and Kim (2013) (n=19) reported adverse effects in 42% (dry mouth in 16%; palpitations in 16%), although no withdrawals because of adverse effects were reported.
Oral glycopyrronium bromide products (glycopyrrolate tablets, USP, Robinul and Robinul Forte; and glycopyrrolate oral solution, Cuvposa) are available in the USA (not licensed for hyperhidrosis). The tablets are contraindicated in medical conditions that preclude antimuscarinic therapy, such as glaucoma, obstructive uropathy, obstructive disease of the gastrointestinal tract, paralytic ileus, unstable cardiovascular status in acute haemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis and myasthenia gravis. There are also warnings about fever and heat stroke as a result of decreased sweating in high environmental temperatures, and diarrhoea, which may be an early symptom of incomplete intestinal obstruction. Listed adverse effects include dry mouth, decreased sweating, urinary hesitancy and retention, blurred vision, tachycardia, palpitations, headaches, nervousness, mental confusion, drowsiness, weakness, dizziness, insomnia, nausea, vomiting, constipation and impotence.
Cost effectiveness and cost
No cost-effectiveness studies of oral glycopyrronium bromide for use in hyperhidrosis were identified.
The NHS Electronic Drug Tariff (May 2013) lists the following prices for glycopyrronium bromide oral solution and suspension in Part VIIIB, Arrangements for payment for specials and imported unlicensed medicines:
-
glycopyrronium bromide 1 mg/5 ml oral solution/suspension: £150.92 for minimal volume of 100 ml plus £0.01 for each extra ml
-
glycopyrronium bromide 2 mg/5 ml oral solution: £262.61 for minimal volume of 100 ml plus £0.14 for each extra ml
-
glycopyrronium bromide 2 mg/5 ml oral suspension: £197.59 for minimal volume of 100 ml plus £0.15 for each extra ml.
No price is listed for glycopyrronium bromide oral tablets, and the cost of these will differ depending on the source. NHS Prescription Cost Analysis for England 2012 reported that various glycopyrronium bromide tablets cost between £268.57 and £712.34 per item (the number of tablets per item is not known).