Dear Mr Perrott
Thank you for your emails dated 20 November and 4 December 2011 regarding the advice in the BNF relating to the withdrawal protocol for benzodiazepines as well as your questions about clorazepate and venlafaxine.
I am glad to hear that the BNF has made an adjustment which is in line with your suggestion to the editor. You have asked if the MHRA might now publicise the adjustment to BNF’s advice on benzodiazepine withdrawal. As you know, the BNF, distributed to NHS doctors and pharmacists, is an independent publication (published jointly by the BMJ Group and the Pharmaceutical Press).
The BNF has effective means of alerting health professionals of important changes. Health professionals have ready access to the publication (in its digital and book versions) and it is used routinely during health professionals’ encounters with patients. Therefore, the BNF itself is a very effective vehicle for alerting health professionals of up to date advice on the clinical use of medicines.
Advice on protocols for clinical disorders such as the management of withdrawal reactions falls outside the MHRA’s remit. In addition, the MHRA cannot readily endorse (or publicise) the advice of other information providers unless the MHRA itself has fully evaluated the evidence that underpins it. Therefore, the MHRA does not have any plans to inform healthcare professions of this recent amendment to the BNF.
Clorazepate (Tranxene) was first authorised in theUKin 1973. Clorazepate was included in the Committee of Review of Medicines (CRM) assessment of benzodiazepines and information about the possibility of withdrawal reactions was included in the CRM’s publication in the British Medical Journal in 1980 which has previously been provided to you. The datasheet for Tranxene was updated to include a warning about possible withdrawal reactions in 1983.
As I explained in relation to Ativan, our records for this period are not complete and I have not been able to establish what caused the delay in adding the information about withdrawal reactions to the datasheet for Tranxene. However, as mentioned in previous correspondence, healthcare professionals have been informed of the need to prescribe all benzodiazepines appropriately since the 1980’s via the BNF and other publications such as the British Medical Journal and the drug safety bulletin “Current Problems” and more recently “Drug Safety Update”. The reasons for the differences in theUKandUSdatasheets have also been explained in previous correspondence and there is no further new information available that would allow us to elaborate on what we have already provided.
You have also asked about the Selective Noradrenaline Reuptake Inhibitor (SNRI) venlafaxine and the information about the risk of withdrawal reactions that has been provided in the product information. It has been known for many years that symptoms can occur on the withdrawal of antidepressants. Syndromes occurring on the withdrawal of tricyclic antidepressants (TCAs) have been defined and severe reactions have been noted on the withdrawal of monoamine oxidase inhibitors (MAOIs). Since the early 1990s, it has become clear that the Selective Serotonin Reuptake Inhibitors (SSRIs) and related antidepressants like SNRIs can also be associated with withdrawal reactions, although different SSRIs and SNRIs appear to cause withdrawal reactions to different extents.
The Summary of Product Characteristics for Efexor, the first venlafaxine product authorised in theUK, contained information that withdrawal effects are well known to occur with antidepressants, and it was therefore recommended that the dosage of Efexor be tapered gradually and the patient monitored. The product information for Efexor has been updated as new evidence has emerged including that relating to the risk of withdrawal reactions. The issue of withdrawal reactions with SSRIs and SNRIs, including venlafaxine has been kept under close review. We are not aware of any evidence to suggest that Wyeth has withheld data on this important issue.
Yours sincerely,
DR J M RAINE CBE
Director, Vigilance, Risk Management of Medicines