- Aust Prescr 1999;22:43-7
- 1 April 1999
- DOI: 10.18773/austprescr.1999.045
Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
20 mg and 40 mg tablets
Approved indication: asthma
Australian Medicines Handbook Section 19.3
In patients with asthma, leukotrienes are associated with airways inflammation and smooth muscle constriction. Zafirlukast has been developed to counteract these effects by competing for the leukotriene receptors.
The drug is taken twice a day. Zafirlukast should not be taken with meals as its bioavailability is reduced by 40%. Zafirlukast is extensively metabolised with most of the metabolites being excreted in the faeces. Although clearance is reduced in the elderly, a lower starting dose is not recommended. The drug is not recommended for patients with hepatic impairment.
The liver metabolism involves the cytochrome P450 system. This explains some of the drug interactions which can occur with zafirlukast. Interacting drugs include warfarin, terfenadine, erythromycin and aspirin.
Zafirlukast has been compared with placebo in short-term studies (13 weeks' duration) of mild-to-moderate asthma. In one of these company-supported studies, 103 patients were given zafirlukast and compared with 43 patients given a placebo. At the end of the study, the zafirlukast group had significantly more days when they did not need their beta agonist inhalers and were free of symptoms.1
This means that some patients with asthma will benefit from taking a preventive medication, but how does zafirlukast compare with other forms of prevention? It is probably no more potent than inhaled steroids and its potential to allow a reduction in the dose of inhaled corticosteroids is uncertain.
Patients should not be suddenly switched from corticosteroids to zafirlukast. There are occasional reports that reducing the dose of corticosteroid may precipitate or exacerbate the Churg-Strauss syndrome (systemic eosinophilicvasculitis). Other adverse events observed during treatment with zafirlukast include headache, gastrointestinal upsets and altered liver function and elevated creatine phosphokinase.
Although zafirlukast has been approved for the treatment and prophylaxis of asthma in patients over 12 years of age, its main role will be in prevention. Zafirlukast has no role in acute asthma attacks and has not been evaluated in unstable asthma. It can be used in patients whose asthma is not controlled by beta agonists. As zafirlukast has no clear advantage, it should probably only be prescribed if the patients cannot use other preventive treatments.