Medicines Healthcare Products Regulatory Agency
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 governments 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 Parkinsons 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 persons 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 a