Policy responses and statements

Name of organisation:

Medicines and Healthcare Products Regulatory Agency (MHRA)

Name of policy document:

ARM 43 - Request to Reclassify a Product from POM TO P - Clamelle (Azithromycin 500mg) Tablets

Deadline for response:

2 August 2007

Background: Comments were sought on the proposed reclassification of this product from POM to P. Azithromycin is a macrolide antibiotic, recommended as a first line therapy for the treatment of uncomplicated Chlamydia trachomatis genital infection, given orally as a one gramme single dose treatment.

COMMENTS ON
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY
ARM 43: REQUEST TO RECLASSIFY A PRODUCT FROM POM TO P  - CLAMELLE (AZITHROMYCIN  500MG) TABLETS

The Royal College of Physicians of Edinburgh is pleased to respond to the MHRA’s consultation letter ARM 43.  The College recognises that there are a range of arguments for and against this particular proposal.

General Comments

The main structure of this argument is whether it is seen as a public good, and the reasoning behind it, or whether there is a real risk of harm over benefit.  There are potential issues of conflict within the ethical framework; although a reclassification may increase patients’ autonomy by allowing less regulated access, it may also produce harm and therefore violate primum non nocere.  The argument for less regulation must be cogently discussed, particularly with regard to the risks posed by increasing access, including its side effect profile, versus its overall benefits if it becomes less regulated by reclassification.

The College understands that such declassification may only bring practical benefit in England, and possibly Wales, via the National Chlamydia Screening Project if patients can access treatment through a pharmacy only after a positive test.

The argument in favour of reclassification

Paragraph 3.5, headed “The opportunity” is clear that reclassification is a public good.  It comments that intervention for preventing pregnancy (emergency contraception) and treatments of Candida and other minor genital conditions already takes place within a pharmacy setting.  This is not by itself a good basis for reclassification.  The argument becomes stronger around the issue of access to appropriate treatment, and through reclassifying the medication it (probably) becomes easier to self treat.  Clearly, a further benefit would be in releasing some pressure on busy GUM clinics and potentially reaching those patients unlikely to seek treatment in such a clinic although, as reported below, this could have other unintended consequences, including reducing the screening for other STIs.

Paragraph 3.6.3 et seq are particularly relevant in that some caveats are established.  The use of the NAAT as a confirmatory test is very relevant, as commercial over-the-counter (OTC) Chlamydia test kits can have a high false positive rate.  However, it may be that a patient with a positive test from whatever source is likely to be offered treatment for Chlamydia, particularly as the worry it engenders is not likely to be removed by a negative NAAT.

The Patient Information Leaflet (PIL) is important, setting boundaries for both the patient and the professional, and establishing important care pathways for the symptomatic patient as well as providing the patient with the means for a more informed choice.  However, there appears to be inconsistency in the advice given to women regarding intercourse after medication – the leaflet advises total abstinence for 7 days and the statement recommends additional barrier protection for 7 days.  These should be consistent.

The argument against reclassification

The argument that reclassification will improve access is weakened by failing to take into account other barriers within this model:

Cost, particularly to a young person, will be a barrier, as will the need still to discuss with a pharmacist the overall management of the sexually transmissible infection (issues of privacy and confidentiality).  There is a free of charge at the point of care service for the management of STIs at all Genitourinary clinics, most family planning/reproductive heath care clinics, and many general practices which are now offering enhanced services for sexual health.  Patient choice is often considered a priority within the decision process, but patients have to be informed that, when attending a pharmacy, they may miss out on a more comprehensive service and may have to pay a charge to reflect the cost of the consultation and prescriptions. In Scotland some CHPs have undertaken to pay for emergency contraception, but it is salutary to consider that there is currently no evidence that supplying free emergency contraception through pharmacies has reduced the rate of unwanted pregnancies in the United Kingdom. Therefore, it would be premature to assume that free access to azithromycin would immediately impact on infection rates.

Although there is little current UK evidence of resistance to azithromycin, there have been a small number of anecdotal reports of reduced sensitivity and experience from the developing world after the introduction of over-the-counter treatment for other STIs.  Perhaps a more worrying argument is the impact of increased (possibly inappropriate) prescribing on gonorrhoea, for which there are fewer effective antimicrobial agents.

Will over-the-counter treatment influence the opportunity to screen for other STIs, as patients access their treatment outside GUM or GP clinics?

Will the availability of over-the-counter treatment influence risk-taking behaviour in terms of unprotected sex - with demands for both post-coital contraceptives and azithromycin?

The assessment of reclassification with regard to POM criteria (para 3.8 et seq)

There is little direct danger to the patient from azithromycin, little risk of misuse, little current resistance to azithromycin, and the use of PIL will minimise any risk.  Although not mentioned in the document, azithromycin is recommended for pregnant women by the World Health Organisation, although current British practice and the azithromycin licence do not reflect this.

An appropriate level of training of pharmacists would be required if they are to dispense this medication.  This should not be underestimated if the full benefits of seeking proper screening and treatment are to be promoted.  Patients should understand incubation periods and sources of infection, as well as an appreciation of future risks including the risk to fertility.

It is important that the treatment is only available to asymptomatic women, and azithromycin is inappropriate for women with PID or epididymitis or other complications.

The treatment of partners requires further thought to ensure that a potential chain of infection is broken.  If a partner is treated without testing, then no further partner notification is possible.  There is an argument for ensuring that partners should only be permitted to obtain azithromycin if they also buy a test kit.

In addition to the successful tracking of partners, there is the important issue of data collection for epidemiological purposes; this will become more difficult with the plurality of providers, unless it becomes a requirement for pharmacists to notify numbers treated to the Health Protection Agency.

Copies of this response are available from:

Lesley Lockhart,
Royal College of Physicians of Edinburgh,
9 Queen Street,
Edinburgh,
EH2 1JQ.

Tel: 0131 225 7324 ext 608
Fax: 0131 220 3939

[2 August 2007]