Further investigation of oxybutynin’s side effects are needed before it can be safely reclassified as a pharmacy (P) medicine, pharmacy bodies have said in response to proposals laid out by the Medicines and Healthcare products Regulatory Agency (MHRA).
On 23 April 2022, the MHRA launched a public consultation on a set of proposals to make Aquiette 2.5mg (oxybutynin hydrochloride; Maxwellia) tablets available from community pharmacies without a prescription. The consultation closed on 13 May 2022.
Aquiette 2.5mg tablets are for the treatment of women aged 18 to 65 years who have symptoms of an overactive bladder that have lasted for more than a month and are not adequately controlled by bladder training alone.
The proposals suggested that in suitable women — and following at least six weeks of bladder training alone — a six-week course of Aquiette could be tried, and if symptoms are then adequately controlled, a further six weeks could be given.
In its response to the consultation, the Royal Pharmaceutical Society (RPS) said that it did not believe that oxybutynin was suitable to undergo the switch from prescription-only (POM) medicine to P medicine.
The response said that there was “mounting evidence” implicating the active ingredient, oxybutynin, with “brain health harm, cognitive decline, the progression of dementia and greater mortality”.
“This ever-increasing evidence of unintentional harm from oxybutynin clearly demonstrates that before it can be considered safe to be moved from POM to P, further investigation of these side effects would be required,” the RPS said.
In June 2021, a paper co-authored by Tony Avery, the incoming clinical director for prescribing at NHS England, concluded that there was sufficient evidence that oxybutynin satisfied the criteria for a causal link with the development of dementia and that alternative bladder medicines should be used where possible.
The RPS’s response also highlighted that the suggested inclusion criteria and review of treatment for Aquiette did not fall in line with current recommendations detailed in the BNF and National Institute for Health and Care Excellence (NICE) guidelines for the treatment of urinary incontinence.
“The BNF and NICE both recommend that prior to any drug treatment commencing, a urine screen should be taken to test for the presence of infection or blood in the urine to help identify underlying causes,” the RPS said.
“A positive test can lead to an urgent referral under certain circumstances, including in patients under 65. This is not required with Aquiette, which could delay the diagnosis of more serious conditions by months.
“This is referenced in the consultation document itself … however, there is no acknowledgement of the potential harm this could cause.”
Pharmacy Forum Northern Ireland (PFNI), the professional leadership body for pharmacists in Northern Ireland, also said it was “against” the move to make oxybutynin available without prescription.
The PFNI’s consultation response said: “The hazards of Aquiette’s anticholinergic side effects especially in older women or those at risk of rapid cognitive decline are well documented.
“Indeed, it is telling that some trusts in GB have removed it from their treatment pathways. The cumulative anticholinergic exposure for older people taking medications for multiple health conditions can be underestimated.”
The response added that the safe supply of Aquiette and the reduction of risk of harm from its use relied on the patient being aware of and reporting the presence of symptoms other than those associated with overactive bladder.
“There is the possibility that the absence, or lack of awareness, of these symptoms could open up the risk of missing more sinister conditions (e.g. ovarian cancer, which can masquerade as other conditions due to the vague symptoms).
“The delay in diagnosis for an underlying condition could pose risks.”
In contrast, the Proprietary Association of Great Britain (PAGB), which represents manufacturers of branded over-the-counter (OTC) medicines, said it was in support of the proposals owing to the medicine’s “well-established safety profile”.
“The assessment made by MHRA highlights the key risks related to using the product, which include: use of the medicine by patients with certain illnesses or conditions; potential side effects in key at risk groups; and drug interactions, including other anticholinergic drugs,” the PAGB said in its response.
“The consultation shows that these risks were mitigated through the [summary of product characteristics], including contraindications, warnings and indications/usage restrictions. Therefore, the incremental risks associated with the supply of the product are minimised.”
The PAGB said it understood that reclassification would “increase awareness” that overactive bladder is a treatable condition and there was an “unmet need” for an appropriate product to be available as a P medicine.
“Expanding the range of medicines available to buy OTC, where appropriate, helps to empower more people to self care, giving them faster, easier access to effective medicines,” the PAGB said.
“It also allows for more appropriate use of NHS resources by reducing the number GP consultations for advice and self-treatable conditions.”
The MHRA told The Pharmaceutical Journal that it could not confirm when the outcome of the consultation would be announced and that no updates could be shared “at this stage”.
A spokesperson for Maxwellia, the licence holder for Aquiette 2.5mg tablets, said that the MHRA continued to “follow their process” and that it would wait for news of the approval of Aquiette “in due course”.
In response to concerns raised by pharmacists at the time of the announcement of the consultation, the company has argued that by introducing Aquiette as an “early, self-care option” it would “drive awareness” of the condition and let women know that there is treatment available.