Healthy Skepticism International News

Novartis Zaditen (ketotifen)

January 1999

Vol 17 Issue 1/2 Contents This month: Novartis’ promotion of Zaditen (ketotifen). Zaditen MaLAM letter Zaditen subscribers' letter News: MaLAM International editions now available via E-mail /www for free.

Novartis promotes Zaditen (ketotifen) in Mexico for asthma.

This month’s edition questions Novartis about the promotion of an antihistamine for asthma in Mexico. Novartis was formed in 1996 from the merger of Sandoz and Ciba Giegy.

A copy of the advertisement appears at the end of this page.

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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:

“disminuye frecuencia, durción e intensidad de las crisis.1,2,3
(decreases the frequency, duration and intensity of [asthma] exacerbations.1,2,3)
“mejora la calidad de vida del paciente 4,5 favoeciendo su tranquilidad y de quienes lo rodean.
(improves the quality of life of the patient,4,5 improving their tranquillity and that of household members.)
“es útil como tratamiento profiláctico del asma.6,7
(is used for prophylaxis of asthma.6,7)
“adminsitración por via oral, sólo 2 veces al dia.8,9
(can be given orally, only 2 doses per day. 8,9)
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

Does Novartis have evidence that Zaditen is useful in both paediatric and adult asthma?
Does Novartis have evidence that Zaditen is useful in moderate or severe asthma?
Does Novartis have evidence that Zaditen is equal or superior to inhaled corticosteroids for asthma prophylaxis?
Is Novartis promoting the use of Zaditen for “pre-asthmatic” children?
Yours sincerely,

Dr Joel Lexchin MD, CCFP (EM), DABEM
Secretary, MaLAM Inc www.camtech.net.au/malam

Dr Daniel Vasella
President
Novartis
CH-4002 Basel
Switzerland

re: the promotion of Zaditen (ketotifen)

Dear Dr Vasella,

I have read the MaLAM International edition about the promotion of Zaditen by Novartis in Mexico. q

(Please tick where appropriate)

I am a: doctor q

pharmacist q

nurse q

……………………….. q

and would appreciate receiving a personal copy of your reply. q

Yours sincerely,