Mr John Perrott
20 Greenacre Court
Lancaster
LA1 4LE
2 June 2011
Dear Mr Perrott
Thank you for your emails of 6 and 7 May 2011 relating to the 1974 data sheet for Ativan and the information held by Wyeth at that time, regarding withdrawal reactions.
Based on the records currently held by the MHRA, it is not possible to establish what information was submitted by Wyeth in relation to the licensing of Ativan or whether Wyeth withheld information about possible dependence and withdrawal reactions. Where we have clear evidence that a manufacturer has withheld important safety data then we would investigate this issue and whilst we note your continued concerns about this being the case for Ativan unless we have clear documented evidence confirming information was withheld at the time of licensing the MHRA is unable to take this issue forward.
As previously stated on 4 June 2010, the MHRA are unable to comment on the scientific basis for the warning about “sleep disturbances” associated with withdrawal from lorazepam, as the records for this period are no longer available. “Sleep disturbances” would have reflected the data that was submitted to the regulatory authority at that time. Although with hindsight, this warning does not appear sufficient given the current knowledge of withdrawal reactions, it is important to remember that all the warnings in the product information have evolved over time as more data have been received. For benzodiazepines, as for many medicines, the warnings that are in place now are much more comprehensive than they were in the 1970’s when the regulation and associated monitoring of the safety of medicines was in its infancy.
Data sheets were not the only source of information available to prescribers. The Committee on the Review of Medicines published their findings in the British Medical Journal (BMJ) in March 1980 in order to reach as wide an audience as possible. The BMJ article recommends short term use of benzodiazepines and lists withdrawal reactions, including convulsions. Information about the need to limit prescribing of benzodiazepines to short term use was also included in the British National Formulary which is distributed to all NHS prescribers each year. Doctors prescribing Ativan in the UK would therefore have had access to information about the risks associated with benzodiazepines from at least 1980 onwards and should have considered stopping treatment in any patients who had received benzodiazepines long term.
Yours sincerely,
DR J M RAINE CBE
Director, Vigilance, Risk Management of Medicines