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Regulatory Agency

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Mr Medawar
Social Audit Ltd
P.O. Box 111
London NW1 8XG

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                                                                                                                                           01 December 2006

Dear Mr Medawar,                                


FOI 06-362

Thank you for your further letter of 3 November about Paroxetine and pimozide.

Thank you for sending me a copy of Sir Ernest Gowers’, Complete Plain Words. There are, as I am sure you are aware, rules governing the receipt of gifts by civil servants. Having consulted the relevant MHRA standard operating procedure I have decided that I am able to accept your gift.

You have raised a number of questions for information under the Freedom of Information Act and I shall answer them in the order in which you raised them.

Please provide documentary evidence to show that the MHRA had, prior to September 2006, formally considered [a] whether and how to alert UK prescribers to the new contraindication (paroxetine+pimozide), other than by means of a small print change in the SPC; and [b] any or all of the four reasons you gave me for deciding to take no action.

No such information is held by the Agency. Agency staff make many decisions each day in the course of the day-to-day business of medicines’ regulation and the outcome of all discussions is not recorded.

2. Did the fact that this matter was being handled through the European drug approval system preclude (effectively prohibit or inhibit) unilateral action by the Agency? In other words, could the MHRA have requested GlaxoSmithKline (and have expected compliance from them) to either take, or agree to, more effective measures to communicate this label change?

The fact that Seroxat is authorised through one of the European procedures, the Mutual Recognition procedure, does not preclude a Member State taking unilateral action to communicate on a national basis about a particular safety issue. However, there is general agreement that ordinarily the aim should be for a consistent approach to communication across Member States in order to avoid any potential confusion. 

3. Please would you explain why the contraindication for pimozide is not referred to in the current SPC for fluvoxamine (taking into account that such a warning has appeared in the US label since June 2000)? Ditto citalopram and escitalopram (US warnings since January 2005).

Due to differences in the way products are used in the USA compared to the UK it is not unusual for there to be differences between the US and UK product information for a particular drug. Updates to the US labelling are not always followed by updates to the UK product information. Although we have good links with the FDA and communicate with them on major safety issues, it is not the Agency’s practice to systematically compare UK SPCs with the product information in all other countries, as it is the responsibility of the Marketing Authorisation Holder to ensure that their Summary of Product Characteristics is kept up to date in line with current knowledge. We will however contact them and ask them to justify any differences between the US and UK product information in relation to warnings about concomitant pimozide use.

4. Does the Agency not accept that the warning in the pimozide SPC – which lists some SSRIs but which excludes paroxetine - is misleading and potentially dangerous – and if not, why not?

As explained in my previous letter we do not consider that the current product information for pimozide is misleading or dangerous as concomitant use of drugs metabolised by cytochrome P450 2D6 (such as paroxetine) is already contraindicated and extensive warnings about the potential for QT prolongation already exist in the pimozide product information. As stated in my previous letter we do accept that the product information could be clearer and we will take this forward.

Yours sincerely

Stephen Fawbert
VRMM FOI Coordinator

We asked the European regulators (EMEA) about this. Their reply (11 December)
implicitly suggests that the ball was in the MHRA's court, and that any failure to warn
was entirely down to the UK authorities. High levels of confusion seem to reign:

"Unfortunately, we cannot provide the information you request as paroxetine containing medicinal products are nationally authorised and therefore this issue is dealt with at national level. The only thing we have published on our EMEA website with regard to paroxetine is the Opinion and Product Information resulting from the Article 31 referral procedure; in the documents published by the EMEA it is made very clear that any subsequent changes (following the referral) will be dealt with at national level."