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Antileukotrienes
Post your experienceThe leukotriene receptor antagonists (LTRAs) montelukast and zafirlukast (available since 1998) have anti-inflammatory and bronchodilator properties.1 They block the effects of cysteinyl leukotrienes in the airways which can get released in response to antigens, aspirin or exercise. They have long half-lives.
They are effective in mild to moderate asthma when used alone or with an inhaled steroid. They may be of benefit in exercise-induced asthma and in those with concomitant rhinitis.3 Montelukast is less effective than a standard dose of inhaled corticosteroid but the two drugs appear to be additive. They are less effective in severe asthma.
LTRAs may be indicated in several clinical situations:4
- In step 2 of the British Guidelines, they can be used as an alternative to inhaled steroids in patients taking short-acting beta-agonists. They are less effective than inhaled steroids and should not be given as the sole preventive in patients taking long-acting beta-agonists (LABAs).
- In step 3 they can be used as an adjunct to steroids if a LABA has failed to control symptoms and increasing the dose of steroids has failed to produce an optimal response. LABA but not LTRA may also be associated with blunting of the reliever response to salbutamol in the presence of bronchoconstriction. LTRAs confer a bronchoprotective effect (e.g. against allergen or exercise) which, unlike LABAs, is not subject to tolerance, even when combined with inhaled steroid. A single dose of a LTRA is effective within one hour and protects for at least 12 hours.5 LTRAs may produce an improvement in lung function, a decrease in exacerbations, and an improvement in symptoms.
- In step 4 LTRAs can be used as an adjunct to inhaled steroids, LABAs and other therapies.
- In step 5, LTRAs can be used as adjunctive treatment to reduce the dose of oral steroids. However, if there is no reduction within six weeks, they should be stopped.
- LTRAs can reduce eye and nose symptoms as effectively as antihistamines. Combined with an antihistamine is more effective than either alone, but this combination is still less effective than intranasal steroids.6 However, they would seem a logical choice for patients with seasonal rhinitis and asthma.
- They have theoretical benefit in aspirin-intolerant asthma, since they are important mediators of this type of asthma, and they can improve symptoms inadequately controlled with steroids but they do not necessarily protect from severe reactions if exposed to aspirin or NSAID. However, apart from rigorous avoidance of NSAIDs, the British Guidelines suggest treating aspirin-intolerant asthma in the same way as any other kind of asthma.
- Montelukast and zafirlukast are generally well tolerated.
- LTRAs should not be initiated in pregnancy, but can be continued in patients whose asthma has been suboptimal on other treatments prior to pregnancy.2
- Unwanted effects include gastrointestinal symptoms (nausea, abdominal pain), headache and skin rashes.
- Transient, asymptomatic elevations in liver transaminases may occur with zafirlukast but not with conventional doses of montelukast.
- Rarely, zafirlukast causes severe hepatotoxicity, so the drug is contraindicated in patients with liver impairment.
- Very rarely, Churg-Strauss syndrome, a systemic eosinophilic vasculitis, has been reported in patients receiving leukotriene receptor antagonists, usually when corticosteroid therapy is reduced or withdrawn.
Document references
- Currie GP, Devereux GS, Lee DK, et al; Recent developments in asthma management. BMJ. 2005 Mar 12;330(7491):585-9.
- British Guideline on the Management of Asthma, British Thoracic Society and SIGN (May 2008)
- British National Formulary
- No authors listed; Leukotriene receptor antagonists--an update. Drug Ther Bull. 2005 Nov;43(11):85-8. [abstract]
- Coreno A, Skowronski M, Kotaru C, et al; Comparative effects of long-acting beta2-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma. J Allergy Clin Immunol. 2000 Sep;106(3):500-6. [abstract]
- Pullerits T, Praks L, Ristioja V, et al; Comparison of a nasal glucocorticoid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol. 2002 Jun;109(6):949-55. [abstract]
- Summary of Product Characteristics, Singulair 10mg Tablets®; Merck Sharpe & Dohme Limited, electronic Medicines Compendium. Text revised October 2007, accessed 06 June 2008.
- Summary of Product Characteristics, Accolate Tablets®;; AstraZeneca UK Limited, electronic Medicines Compendium. Text revised May 2008, accessed 06 June 2008.
DocID: 261
Document Version: 2
DocRef: bgp2275
Last Updated: 14 Jul 2008
Review Date: 14 Jul 2009
The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.
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