Consultation on proposal to make Aquiette 2.5mg Tablets (oxybutynin hydrochloride) available from pharmacies
Detail of outcome
1. Scope of the report and Background to public consultation
The scope and purpose of this report is to detail the outcome of the public consultation and subsequent decision of the procedure for reclassification of Oxybutynin Hydrochloride. This report confirms the medicine is safe for patients under appropriate medical supervision; it is not intended to be an assessment report.
1.1 Consultation documents for ARM 102 which summarise the proposed reclassification from a prescription only medicine (POM) to pharmacy (P) medicine of Aquiette 2.5mg Tablets containing oxybutynin hydrochloride for treatment of longstanding (˃ 1 month) overactive bladder symptoms, i.e., urinary urgency and frequency without dysuria, which may occasionally lead to incontinence in women between 18 and 65 years of age, were posted on the GOV.UK website on 23 April 2022.
The deadline for comments was 13 May 2022. ARM 102 documents can be accessed from Proposal to make Aquiette 2.5mg Tablets (oxybutynin hydrochloride) available from pharmacies
1.2 To be reclassified from POM to P, a medicine must:
- be unlikely to be a direct or indirect danger to human health when used without the supervision of a doctor, even if used correctly.
- be generally used correctly (i.e., not frequently or to a wide extent used incorrectly)
- not contain substances or preparations of substances where the activity of the product or its side effects require further investigation.
- not normally be prescribed by a doctor for injection (parenteral administration)
1.3 In the UK, these criteria are laid down in the Human Medicines Regulations 2012, regulation 62(3).
The public consultation (ARM 102) was conducted to seek wider views on the reclassification proposal for Aquiette from prescription only medicine to pharmacy availability, prior to a final decision by the MHRA. Following a review of the unprecedented number of responses to the public consultation and the expert opinion of the government’s independent advisory committee on medicines safety, the Commission on Human Medicines (CHM), which, in light of newer and emerging evidence concerning the safety of oxybutynin hydrochloride (the active ingredient in Aquiette), advised against the reclassification of Aquiette to pharmacy status; a decision was made to retain the POM status for this medicine.
2. Background on anticholinergic medicines
2.1 Active ingredient in Aquiette (oxybutynin hydrochloride)
The active ingredient in Aquiette, oxybutynin hydrochloride, belongs to a group of medicines known as anticholinergics (also known as muscarinic receptor antagonists).
Anticholinergic medicines may be prescribed by doctors to treat a variety of conditions including chronic obstructive pulmonary disease (COPD), bladder conditions, gastrointestinal disorders, and symptoms of Parkinson’s disease.
2.2 Anticholinergic activity and adverse effects
Anticholinergic medicines act by blocking the action of a neurotransmitter known as acetylcholine. This inhibits nerve impulses responsible for voluntary muscle movements and various bodily functions.
Effects of anticholinergics peripherally (outside the brain and the central nervous system) include dry mouth, dry eyes, constipation, and difficulty passing urine.
Central effects (on the brain and the central nervous system) of anticholinergics may include cognitive effects such as difficulty thinking and remembering, mental confusion, dizziness, poor attention, inability to concentrate, delirium, confusion, and restlessness.
2.3 Anticholinergic burden
Anticholinergic burden is defined as the cumulative effect of using one or more drugs with anticholinergic activity. Various scales and indices exist for calculating anticholinergic burden in patients. The Anticholinergic Cognitive Burden (ACB) score (see 2.4) is one such scale used by healthcare professionals.
2.4 Anticholinergic Cognitive Burden (ACB) score
The ACB scale is a method of quantifying the risk of harmful cognitive effects in people taking medicines with anticholinergic activity. The scale ranges from 0 to 3, with a score of 0 (zero) given to medicines with no anticholinergic activity to the highest score of 3, for medicines with strong evidence of anticholinergic effects on the brain. A person’s total ACB score is calculated by adding up the scores for any medicines that they take. A total ACB score of 3 or more may increase the risk of cognitive impairment, functional impairment, falls and mortality in older adults (˃ 50 – 65 years of age).
Oxybutyinin hydrochloride, the active ingredient in Aquiette has an ACB score of 3, meaning it has strong anticholinergic effects on the brain and therefore contributes significantly to anticholinergic burden.
3. Summary of responses to consultation
3.1 A total of 2033 complete responses were received, 1640 (81%) of which were in favour of reclassification, 328 (16%) were against reclassification and 65 (3%) were undecided (not sure).
The majority of responses in favour of reclassification were from patients and/or members of the public (97%). The majority of responses against reclassification were from healthcare professionals and professional bodies/associations (78%). The highest percentage of responses undecided about the reclassification were from patients/members of the public (71%).
3.2 A breakdown of the 1640 responses in support of the proposal is as follows:
- patients/members of the public (97%)
- healthcare professionals (pharmacists, GPs, consultants, nurses) (2%)
- professional organisations/associations (1%)
3.3 A breakdown of the 328 responses against the proposal is as follows:
- healthcare professionals (pharmacists, GPs, consultants, nurses, physiotherapists) (75%)
- patients/members of the public (20%)
- professional organisations/specialist associations (3%)
- academics (2%)
Of the healthcare professionals responding ‘no’, 52% were pharmacists, 19% consultants (neurologists, geriatricians, urologists, old age psychiatrists), 15% specialist nurses/physiotherapists and 13% GPs.
Of the professional bodies/associations responding, 69% were against the proposal to reclassify Aquiette.
3.4 A breakdown of the 65 respondents who were undecided (not sure) about the proposal is as follows:
- patients/members of the public (71%)
- healthcare professionals (26%)
- specialist associations (3%)
3.5 All the responses received have been carefully considered and analysed. Due to the large number of responses a decision has been made not to publish individual responses. Key issues and concerns raised by respondents are summarised below.
4. Responses against the proposal to reclassify Aquiette as a pharmacy medicine
Responses against reclassification of Aquiette were received from healthcare professionals, professional bodies and associations and patients.
4.1 Responses from healthcare professionals
Of the individual healthcare professionals responding, 83% were opposed to the reclassification.
4.1.1 Key issues raised by healthcare professionals in opposition to the reclassification of Aquiette were:
i) Concerns over the suitability of the active ingredient oxybutynin hydrochloride for pharmacy supply
- increased potential for serious side effects
- potential to increase anticholinergic burden with increased risk of dementia if used long-term.
- cognitive impairment (trouble remembering, learning new things, concentrating), even when used in under 65s and with low dose.
- risk of exposing younger patients to anticholinergics over longer periods in their lifetime.
- use of this drug with high ACB score of 3 is at odds with current clinical practice which discourages use of oxybutynin in favour of alternative drugs with lower anticholinergic burden.
ii) Concerns over supply of Aquiette in pharmacies
- by-passing NICE guidance
- complexity of diagnosis of overactive bladder (OAB)
- masking of other conditions/delay in diagnosis of more serious conditions
- potential for patients to view this as a one-size fits all (quick fix) to a complex problem.
- lack of access by pharmacists to patient records, with risk of prolonged treatment/ lack of continuity of care
- shifting cost onto the patient with potential for inequality of access
4.2 Responses from patients
Patients with first-hand experience of living with OAB or other bladder conditions expressed views against the reclassification, citing reasons such as poor tolerability of oxybutynin, its potential to cause cognitive impairment, including dementia with long-term use and the importance of correct diagnosis of their condition by a doctor.
4.3 Responses from professional bodies/specialist associations
Of the professional bodies/associations responding, 69% provided a negative response to the proposal to reclassify Aquiette.
These included the following:
- Royal Pharmaceutical Society (RPS)
- College of Mental Health Pharmacy (CMHP)
- Pharmacy Forum Northern Ireland
- Primary Care Pharmacy Association
- Pharmacists’ Defence Association (PDA)
- British Medical Association (BMA)
- British Geriatric Society (BGS)
- Pelvic Obstetric Gynaecological Physiotherapy (POGP) professional network of the Chartered Society of Physiotherapy.
A significant number of detailed comments in opposition to reclassification of Aquiette were received from professional bodies and associations on grounds of patient safety and negative benefit to risk associated with oxybutynin hydrochloride in the pharmacy (P) setting.
4.3.1 The key concerns raised by professional bodies/associations in opposition to the reclassification of Aquiette aligned with those expressed by individual healthcare professionals and included the following:
- potential masking of symptoms with delay in diagnosis of a more serious condition, which may lead to the worsening of an undiagnosed condition.
- potential for ‘ordering online’ and ‘internet prescribing’ mechanisms being used for the inappropriate self-treatment of a condition such as this (overactive bladder)
- without access to patient notes, it could be challenging to determine its suitability in patients who do not fully disclose all current and previous medical diagnoses.
- in many areas across GB prescribing of oxybutynin has been limited due to the unacceptable side effect profile of the medication and to reduce the risk of increasing the anticholinergic burden in patients.
- questionable value, compared to the risk, in patients’ self-managing a previously undiagnosed condition, at cost, for a maximum of 12 weeks (if patient follows the advice strictly) for a condition that will likely continue after the treatment period.
- risk of patients obtaining this from multiple pharmacies
- risk of women seeking pharmacological intervention without first following the evidence-based primary approach of bladder training with the support of an appropriately qualified professional to assess and provide follow-up.
- whilst overactive bladder is a condition for which better access to medication, after diagnosis and a non-pharmacological treatment trial would be desirable, a community pharmacy is not an appropriate setting to determine diagnosis nor monitor lifestyle measures.
- the health of anyone taking anticholinergic medication, regardless of age, needs close monitoring; the side effect profile and contraindications / precautions list for oxybutynin is wide-ranging.
- switching this from POM to P could increase risk of enhanced anticholinergic burden due to the lack of monitoring, leading to increased side effects.
- concern that efficacy is not sufficient compared with more conservative measures and that patients might dismiss this whole class of medication because the OTC medicine didn’t work for them.
5. Responses in favour of the proposal to reclassify Aquiette as a pharmacy medicine
The majority of responses in favour of reclassification were from patients and/or members of the public (97%). Healthcare professionals made up 2% of responses in favour, with the remaining 1% being from professional organisations/associations.
Patients responding in favour of reclassification made it evident that there is an unmet need for improved access to treatment for OAB. Key points included greater ease of access to treatment, reducing pressure on GPs, increased awareness of OAB and removal of the embarrassment and stigma associated with discussing it.
5.1 Responses from patients
Some extracts from comments received form patients include the following:
- `…we urgently need easily accessible help for women, their families and friends who suffer the effects of it.
- `… there are very many women struggling with an overactive bladder, and we need help especially when advice re retraining one’s bladder etc is so incredibly hard to do
- `This is such a widespread problem…& can be very limiting when all you want to do is to lead a normal life.
- `The personal & sensitive nature of the problem has allowed it to go under the radar for far too long and there are many who are at a complete loss of how to deal with it.
5.2 Responses from healthcare professionals
Healthcare professionals made up 2% of responses in favour of reclassification. The minority of healthcare professionals responding in favour of reclassification, acknowledged anticholinergic burden and antimuscarinic side effects and drug interactions associated with oxybutynin, despite being in favour of reclassification.
5.3 Responses from professional organisations/associations
Professional organisations/associations responding in favour of reclassification included:
- Proprietary Association of Great Britain (PAGB)
- Community Pharmacy Northern Ireland
- National Pharmacy Association (NPA)
- Healthcare Improvement Scotland
- Community Pharmacy Patient Safety Group & the CCA (Company Chemists’ Association) Professional Practice Group.
One association noted that availability of Aquiette through pharmacies would aid in addressing much of the current backlog of GP appointments. It was acknowledged that the clinical assessment and consultation with the patient should be carried out by the pharmacist and not be delegated to other pharmacy staff.
Another association while responding in favour of the reclassification of Aquiette, acknowledged concern over risks associated with delay in diagnosis of potentially more serious conditions and purchase of multiple packs of the product by the patient.
A professional practice group responding in favour of the reclassification and improved access for women to treatment of health problems, including urinary incontinence where appropriate, acknowledged the emerging evidence concerning possible causal link with dementia and anticholinergic medicines such as oxybutynin and the need for careful consideration of how such concerns may be communicated to patients.
6. Responses undecided (not sure) about the proposal to reclassify Aquiette as a pharmacy medicine
65 responses were undecided about the proposal to reclassify Aquiette.
Healthcare professionals, including pharmacists, consultants and GPs acknowledged the need for wider access to treatment for OAB and greater awareness of the condition, but also raised concerns such as side effects and anticholinergic burden associated with oxybutynin and potential for missed underlying conditions/misdiagnosis.
Specialist nurses acknowledged the need for better services for women with bladder problems, but also expressed concern that assessment of bladder symptoms is complex, requiring specialist input, to ensure other conditions do not go untreated or are missed.
Undecided patients expressed concern over potential for masking underlying conditions/misdiagnosis and side effects of oxybutynin. Some patients also noted from their own experience of treatment that correct diagnosis of bladder symptoms is time consuming, often with the need to try several different treatments before finding a suitable one. There was also concern that patients may circumvent the system by responding at consultation to the pharmacist in such a way as to fit the ‘supply model’ for Aquiette and therefore be able to purchase it.
7. Main issues raised
7.1 It was evident from comments in favour of reclassification, that there is an unmet need for improved access to treatment for OAB. Key points made by respondents included:
- greater ease of access to treatment
- reducing pressure on GPs
- increased awareness of OAB and removal of the embarrassment and stigma associated with discussing it.
7.2 However, opposition to the reclassification, primarily from healthcare professionals and professional bodies/associations, was evident, with concerns expressed over the active ingredient in Aquiette (oxybutynin hydrochloride). Oxybutynin is known to cross the blood brain barrier and exert effects on the brain. Respondents to the consultation cited publications relating to possible association between anticholinergic OAB medicines, cognitive impairment, and risk of dementia. Other publications noted an inconsistency in findings as to such an association. Much of the literature is very recent and this is an area of increasing interest and concern to clinicians.
7.3 Healthcare professionals/professional bodies responding to the consultation highlighted that in some parts of GB, it was now clinical practice to reduce prescribing of oxybutynin due to concerns over anticholinergic side effects and associated anticholinergic burden. The proposal to make oxybutynin more freely available as a pharmacy medicine, despite proposed risk minimisation measures proposed for Aquiette as a `P’ medicine is at odds with current clinical practice.
7.4 Some respondents to consultation raised concerns over risk of exposing younger patients to anticholinergic effects over a longer period in their lifetime, should Aquiette become available in pharmacies.
7.5 Other concerns expressed over the proposal to reclassify Aquiette included by-passing of NICE guidance, complexity of diagnosis of OAB, masking of underlying conditions with delay in diagnosis of more serious conditions, lack of access by pharmacists to patient medical records and the shifting of costs onto the patient with potential for inequality of access.
8. Conclusion
8.1 Careful assessment of the significant number of responses to consultation on the reclassification of Aquiette 2.5mg Tablets for treatment of longstanding (˃ 1 month) overactive bladder symptoms, i.e., urinary urgency and frequency without dysuria, which may occasionally lead to incontinence in women between 18 and 65 years of age, has identified some safety concerns associated with the supply of such a product in the pharmacy setting.
8.2 After careful consideration of advice from CHM and all available evidence on the safety of Aquiette, including the responses to the public consultation, the Licensing Authority has taken the decision that the POM criteria, in particular criterion 1 (the product is likely to present a direct or indirect danger to human health even when used correctly, if used without the supervision of a doctor) and criterion 3 (further investigation of the activity and/or side effects is required) apply to Aquiette.
The MHRA has therefore refused the reclassification to pharmacy (P) medicine status for Aquiette.
8.3 Patients will still be able to access oxybutynin with a prescription from a qualified healthcare professional. This will ensure that the medicine is used safely and appropriately under medical supervision.
MHRA
June 2023
Original consultation
Consultation description
Aquiette 2.5mg Tablets are a medicine for treatment of long-standing (present for over 1 month) symptoms of overactive bladder (OAB) which are not adequately controlled by bladder training alone, in women 18 to 65 years of age. We propose to make it available through pharmacies.
Aquiette tablets contain oxybutynin, an anticholinergic medicine and are intended to treat symptoms of OAB at the milder end of the spectrum of this condition including urgent need to urinate, frequent urination, sometimes leading to accidental leaks. Aquiette is not suitable for treating symptoms of stress incontinence alone such as accidental leakage of urine during exercise, when coughing or when sneezing.
In suitable women and following at least 6 weeks of bladder training alone, a 6 week course of Aquiette may be tried. If symptoms of OAB are adequately controlled, a further 6 weeks treatment may be given. A maximum of 12 weeks treatment may be provided in the pharmacy.
Medicines containing oxybutynin, the active ingredient in Aquiette will still be available on prescription. Women will have a choice in where they obtain supply of this medicine from, either on prescription or from pharmacies.
We consider that this product may be available as a pharmacy (P) medicine.
The Commission on Human Medicines has advised that this product could be made available as a Pharmacy (P) medicine.
We want to know what you think about this proposed change.
Please use this form to tell us your views.
The deadline for comments is 23:45PM, 13 May 2022.
Below you will find:
- A summary of the proposed change and the background
- A copy of the proposed patient information leaflet, label, and Summary of Product Characteristics if the change goes ahead
- A form for your response
Documents
Last updated 3 July 2023 + show all updates
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Publication of outcome to consultation.
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First published.