Montelukast sodium

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.

Singulair (Merck Sharpe & Dohme)
10 mg film-coated tablets
5 mg chewable tablets

Indication: asthma

AMH Section 19

Asthma involves bronchoconstriction and inflammation of the airways. If a patient's asthma is to be well managed, it may be necessary to control the inflammation as well as the bronchoconstriction. The most commonly used preventive drugs are inhaled corticosteroids and sodium cromoglycate. Montelukast offers a new approach.

The inflammatory process is thought to involve chemical mediators called leukotrienes. The leukotrienes are also involved in bronchoconstriction. As montelukast competes with leukotrienes for their receptors, it can inhibit their effects.

The two formulations of montelukast are not bioequivalent. The bioavailability of the film-coated tablet is 64%. The chewable tablet, for children, has a bioavailability of 73% which is decreased to 63% by food. Bronchodilatation occurs within two hours of taking a dose.

Montelukast is metabolised in the liver with most of the metabolites being excreted in the bile. Although cytochrome P450 3A4 may be involved, it is unlikely to be inhibited by therapeutic concentrations of montelukast.

Placebo-controlled studies have found that a bedtime dose of montelukast reduces asthma symptoms and use of beta agonists. Lung function tests also improve. Although extension studies suggest the benefits of treatment continue, the pivotal trials were evaluated after 12 weeks.

Another study lasting 12 weeks compared montelukast and beclomethasone. While both treatments were significantly better than placebo, beclomethasone produced a greater improvement than montelukast. Patients inadequately controlled by inhaled steroids may benefit from the addition of montelukast. Likewise, the addition of montelukast may allow some patients to reduce their dose of inhaled corticosteroids. Any reduction must be done gradually.

Patients taking montelukast are more likely to complain of headache or gastrointestinal symptoms, such as abdominal pain or dyspepsia, than those given a placebo.

At present, montelukast is unlikely to be the first choice drug for the control of asthma. Montelukast should not be relied on to treat acute asthma and it is less effective than inhaled steroids. It would be interesting to know how the paediatric formulation compares with sodium cromoglycate in childhood asthma. Until more information is available, montelukast will probably be used when a patient's asthma is not completely controlled by existing preventive drugs.