Montelukast Sodium Tablets for Asthma
By William T. Elliott, MD, and James Chan, PharmD, PhD
The food and drug administration has approved a new once a day leukotriene antagonist for the treatment of asthma. Merck's montelukast (Singulair) is the second FDA-approved leukotriene receptor antagonist and the third antileukotriene drug for this indication. Leukotriene modifiers represent a new class of anti-inflammatory drugs for asthma. Currently available drugs include zafirlukast (Accolate), another leukotriene receptor antagonist, and zileuton (Zyflo), a 5-lipoxygenase inhibitor. These agents are being promoted as oral alternatives to inhaled corticosteroids. Leukotriene modifiers are used for maintenance therapy only, and have no role in acute asthma, although they may be continued during an asthma attack.
Montelukast is a selective inhibitor of the cysteinyl leukotriene CysLT1 receptors.1 Blockade at these receptors inhibits the action of cysteinyl leukotrienes (LTC4, LTD4, and LTE4). These leukotrienes mediate bronchoconstriction, promote vascular permeability, mucus secretions, and mucosal edema, and appear to have an important role in the pathogenesis of asthma.2,3
Montelukast is not only the first once a day drug in this class, but also the first antileukotriene to be approved for use in children.
Montelukast is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 6 years of age and older.
Montelukast is the only leukotriene modifier that is dosed once day. Zileuton is dosed four times daily, while zafirlukast is dosed twice daily. It is also the only drug of this class FDA approved for use in patients younger than 12 years of age. No significant caution is recommended for drug interactions by the manufacturer. Clinical monitoring is recommended if montelukast is co-administered with potent cytochrome P450 enzyme inducers (e.g., phenobarbital, rifampin).1 In contrast to zileuton and zafirlukast, montelukast does not interact with warfarin.
Montelukast and other currently marketed leukotriene modifiers are, are used primarily as corticosteroid-sparing drugs. However, all these drugs are less potent than corti-costeroids as anti-inflammatory agents. These agents are currently recommended as alternatives to low-dose inhaled steroids or cromolyn or nedocromil in mild persistent asthma.4 Leukotriene modifiers have no role in the treatment of acute asthma, although they may be continued during acute exacerbations. Most commonly reported side effects were headache (18%), influenza (4.2%), and abdominal pain (2.9%). The incidences of these side effects, however, were not significantly different than with placebo.1
Montelukast is supplied as 5 and 10 mg tablets. The 5 mg dose is chewable. For adults and adolescents 15 years of age and older, the dose is 10 mg daily taken in the evening. For children 6-14 years of age, the daily dose is a 5 mg chewable tablet taken in the evening. Montelukast may be taken without regard to meals. No dosage adjustment is recommended in patients with renal insufficiency or in patients with mild to moderate hepatic insufficiency.1
Montelukast is the second cysteinyl leukotriene CysLT1 receptor antagonist to be approved by the FDA. It has been shown in clinical trials to improve parameters of asthma control in both adults and children compared to placebo. These parameters include forced expiratory volume in one second (FEV1), symptom scores, exacerbation days, asthma-free days, and use of beta agonist.1,5-7 FEV1 is improved by about a 5-9% point difference from baseline when compared to placebo.1,5,6 It appears that clinical improvement was irrespective of inhaled steroid use.5,6 Some studies were conducted using high doses of montelukast; however, there appears to be no additional bene- fit with doses above 10 mg daily.1,7 Montelukast has been reported to allow significant tapering of inhaled steroids in patients requiring moderate to high doses of steroids.8 Caution and monitoring are recommended if tapering of systemic steroids is being considered. Churg-Strauss syndrome, characterized by pulmonary infiltrates, eosinophilia, and cardiomyopathy has been reported in patients who were started on zafirlukast and withdrew their steroids.9 The authors suggest that these patients may have had a primary eosinophilia infiltrative disorder controlled by steroid therapy but unmasked by steroid withdrawal facilitated by zafirlukast. These patient generally improve significantly upon initiation of oral steroids or the addition of cyclophosphamide.9
Inhaled corticosteroids are still the cornerstone of anti-inflammatory therapy as recommended by the NIH guidelines. Leukotriene modifiers are currently recommended as alternatives to corticosteroids and cromolyn or nedocromil in prophylaxis and chronic treatment of mild persistent asthma. Montelukast may offer some advantages over the other leukotriene modifiers, such as once daily dosing, approval for pediatric use, no reported clinically important drug interactions, and no routine liver function testing. There are currently no comparative trials between montelukast and zafirlukast or zileuton.
The wholesale cost of montelukast is $2.35 per day for both the 10 mg and 5 mg doses. This cost places it between zafirlukast and zileuton.