January 1999
Dr Daniel Vasella
President
Novartis
CH-4002 Basel
Switzerland
re: the promotion of Zaditen (ketotifen)
Dear Dr Vasella,
A Mexican doctor has asked MaLAM <1> to write to you about the advertisement for the antihistamine Zaditen (ketotifen) published in his country. This advertisement claims that Zaditen:
Comparison of your claims with initial conclusions based on the scientific literature available to MaLAM, summarised below, raises some questions. This letter is intended to give you the opportunity to express your point of view so that we can assess whether your claims assist appropriate therapy. We hope that you will either provide evidence to support your claims or reconsider the promotion of Zaditen. We are optimistic that dialogue can lead to improvements in drug promotion to the benefit of the public, health professionals and your company.<2>
Initial conclusions from the scientific literature.
MaLAM was unable to obtain any of the five references used to support your first two claims. The first and third references appear to be in Spanish, the fifth appears to be in Japanese. The second and fourth references were not in any of the libraries we consulted and were not indexed in Medline. Therefore, we are unable to determine if the references you cite substantiate your first two claims:
Your third claim is that Zaditen is used as prophylaxis for asthma. Your sixth reference <3> reports that a placebo controlled study of Zaditen in "preasthmatic" children found that over a three year period fewer children on Zaditen went on to develop asthma. While this is an interesting finding, it does not correspond with the usual meaning of prophylaxis in the context of asthma.
Furthermore, there are three methodological defects which decrease confidence in that finding: 1) there is no mention of randomization> 2) Although the study is double-blinded it is conceivable that both the treating physicians and the parents could have distinguished between Zaditen and placebo because of the sedating effects of Zaditen 2) The results do not mention if there was any difference in side effects between the two groups. Your seventh reference <4> is to a study comparing different formulations of Zaditen without a control group. In the absence of a control group the efficacy of Zaditen cannot be properly determined.
Your final claims are that Zaditen can be administered orally and only needs to be used twice daily. These claims are supported by the two papers cited.<5,6> However, one of them,<5> although a retrospective study, concluded that inhaled corticosteroids might be better than Zaditen in the treatment of long-standing asthma. This last point addresses additional concerns that MaLAM has with your promotion for Zaditen, specifically the lack of any mention of Zaditen's relative value in the treatment of asthma. Your advertisement does not differentiate between adult and childhood asthma or among degrees of asthma severity implying that Zaditen is useful for patients of all ages and with any degree of severity. A meta-analysis of randomised clinical trials of antihistamines in adult asthma <7> concluded that, on the available evidence, antihistamines, including Zaditen, do not improve asthma control. Neither the Canadian <8> nor the British <9> guidelines for asthma management recommend Zaditen for adult asthma. Even for paediatric asthma both guidelines assign Zaditen a secondary role behind inhaled corticosteroids. The Canadian guidelines recommend Zaditen for children under the age of five with mild asthma where "toxicity or fear of toxicity from corticosteroids is a major concern." The British guidelines do not include Zaditen in the charts outlining the stepped approach to treatment in children but do state in a footnote that Zaditen "may be of some help in very young children intolerant of other drugs."
Questions
Yours sincerely,
Dr Joel Lexchin MD, CCFP (EM), DABEM
Secretary, MaLAM Inc www.camtech.net.au/malam