Comparison between the two leukotriene receptor antagonist antiasthmatics montelukast (Singulair) a

Fråga: Comparison between the two leukotriene receptor antagonist antiasthmatics montelukast (Singulair) and zafirlukast (not approved in Sweden).

1) Are there structural similarities indicating a high theoretical risk of cross reactivity regarding Churg-Strauss syndrome?

2) Are there any studies comparing the clinical effects of the two substances?

3) Have adverse effects on the nasal mucosa or eosinophilic vasculitis been described for montelukast?

The question concerns a 40-year-old woman with astma, currently treated with Pulmicort (budenoside) and Nasonex (mometasone). Treatment with Singulair (montelukast) is considered.

Sammanfattning: There are several case reports of Churg-Strauss syndrome in patients treated with zafirlukast and one case during montelukast medication. Many of these patients received steroids prior to the leukotriene antagonist treatment, and it has been suggested that the Churg-Strauss syndrome could have been a pre-existing condition unmasked by steroid withdrawal. Structurally, montelukast and zafirlukast have little resemblance. No studies comparing the effects of montelukast and zafirlukast were found.

Svar: Churg-Strauss syndrome is a granulomatous vasculitis affecting multiple organ systems. It is also associated with asthma and peripheral eosinophilia.

There are several case reports associating zafirlukast with Churg-Strauss syndrome. However, in several of these patients, systemic steroids were withdrawn as zafirlukast medication started (1). It has therefore been suggested that the Churg-Strauss syndrome in these patients was not a result of zafirlukast treatment, but a pre-existing condition unmasked by steroid cessation.

1) Structurally, zafirlukast and montelukast have little similarity, but it cannot be excluded that their folded three-dimensional structures share common properties (2-3).

2) No studies comparing the clinical effects or adverse effects of montelukast and zafirlukast were found in Medline, in Drugline or in standard pharmacological literature.

3) In Swedis, there are 97 reports of adverse effects of montelukast, where a causal relationship to montelukast medication has been deemed possible or probable (4). Of these reports, one concerned acute rhinitis after provocation test with montelukast and one concerned vasculitis after six weeks of treatment with montelukast. There is one published case report of Churg-Strauss syndrome with pulmonary infiltrates following montelukast treatment (5). However, this patient received systemic steroids prior to montelukast and it cannot be excluded that cessation of the steroids unmasked a pre-existing Churg-Strauss. 1 Zafirlukast. Drugdex(R) System; Micromedex, Inc., Englewood, Colorado (Edition expires (date 3/2001))

2 FASS 2000 (The Swedish catalogue of approved medical products)
3 Zafirlukast. Product information from AstraZeneca
4 Swedis (The Swedish Drug Information System)

5 Franco J, Artes MJ: Pulmonary eosinophilia associated with montelukast. Thorax 1999; 54: 558-560