April 2008

Rationale for reclassification

We agree that pharmacists are well placed to provide prompt treatment to patients suffering from cystitis. Community pharmacists already advise patients presenting with the symptoms of cystitis on appropriate measures to manage their symptoms. In a few parts of the country pharmacists are able to supply appropriate antibiotic treatment, usually trimethoprim and occasionally a cephalosporin, via a Patient Group Direction (PGD). We don’t know of any instances where nitrofurantoin is the treatment which is supplied for the treatment of cystitis via PGD.

The NPA has some concerns about the rationale for reclassification for nitrofurantoin. Its use in the UK is low as stated in the application (6% is the actual figure in the document referenced in the application) (Naber. J Antimicrobial Chemotherapy 2000; 46 Suppl 1). We believe that the current figure is even lower.  Usage is low because it would appear that nitrofurantoin is not the treatment of choice for urinary tract infections (UTIs) in either primary or secondary care.

Trimethoprim is the drug of choice for UTIs with a cephalosporin, (cefadroxil or cephalexin) the second line treatment. Microbiologists, for example those at The Guys and St Thomas’s Hospital NHS Trust and the Cheshire Hospital NHS trusts, would question the use, by community pharmacists, of nitrofurantoin as a first line treatment for UTIs when this is not in line with local protocols.

General practitioners would also question the use of a treatment that doesn’t follow local protocols and that may cause anxiety to their patients who know that this is not the treatment they would have been prescribed by their doctor.

Community pharmacists may also have concerns about supplying a medication which they know not to be the treatment of choice and the supply of which is flouting hospital and primary care best practice guidance. They are likely to prefer to supply trimethoprim if that were being supplied in other health care settings.

Resistance to Nitrofurantoin

The NPA is aware that there are concerns from other stakeholders that reclassification from POM to P of an antibiotic will result in a significant increase in use which may increase the risk of antibiotic resistance. The NPA does not support this view. Patients seeking treatment for cystitis from a pharmacy will be carefully assessed by the pharmacist. The availability of an antibiotic for the treatment of cystitis (from a pharmacy) will mean that some patients receive treatment from a pharmacy instead of from their GP. Pharmacists will also help minimise the development of resistance by ensuring that patients only receive the product when appropriate and by careful counselling on the importance of completing the course of treatment. The advantage for cystitis suffers is they will be able to access treatment promptly without enduring symptoms whilst waiting for a doctor’s appointment.

Credibility of the submission

The NPA also has some concerns about the credibility of this submission for Cystobid 100. It bears remarkable similarities to the ARM 30 (submitted in 2005) application for the reclassification of Cysticlear from POM to P. In fact in the Patient Information leaflet submitted for Cystobid the information would appear to have been ‘cut and pasted’ from the ARM 30 document, the instance being on page 2 of the PIL, section, Take Special Care, third bullet point includes the brand name ‘Cysticlear’ which is the brand name for trimethoprim in the ARM 30 submission. This leads us to question the quality and validity of the information submitted in the remainder of the document and it was felt important to draw this to the attention of the MHRA.

Pharmacy training

The NPA cannot comment on the pharmacy training as we have not had sight of it.

Safety profile

Nitrofurantoin has been available since 1950, its only indication is for the treatment of UTIs, and its usage for this indication is declining.

Although reports of serious side effects are rare the less serious side effects, nausea, headache, diarrhoea and discolouration of urine, are very common and these are likely to make Cystobid 100 unacceptable to a number of patients. Pharmacists counsel patients on the use of their medication and possible side effects including how to mitigate side effects. The patients who will be supplied with Cystobid over the counter will have been treated for cystitis previously and it is unlikely they will have been treated with nitrofurantoin. Whilst patients will usually accept an alternative treatment which they perceive to be better they are unlikely to accept a treatment from which they are more likely to suffer side effects. This is not a particular problem for pharmacy only supply but it is likely to mean that the supply of the product will require significant time for patient counselling and it is important that in promoting the product to the public this message is carefully delivered.

Overall benefit: Risk assessment

Overall the NPA welcomes the possibility that pharmacists will be able to have access to a P category antibiotic to treat cystitis in women and is confident that pharmacists will supply it appropriately and responsibly; thus minimising the risk of a significant increase in overall use and subsequent spread of resistance. However there are some concerns about the reclassification of nitrofurantoin instead of trimethoprim for the reasons detailed above.