There are few adverse effects directly associated with inhibition of leukotriene synthesis or function. This likely is due to the fact that leukotriene production is limited predominantly to sites of inflammation.

Zafirlukast and Montelukast

In large clinical studies the adverse-effect profiles of these drugs were similar to that observed with placebo treatment. Very rarely, patients taking these drugs develop systemic eosinophilia and a vasculitis with features similar to Churg-Strauss syndrome. This problem, often associated with a reduction in glucocorticoid therapy, may represent the unmasking of a preexisting disease. Zafir-lukast, but not montelukast, may interact with warfarin and increase prothrombin times, which should be monitored in patients subject to this interaction.


In ~4—5% of patients taking zileuton, there is an elevation in hepatic transaminases, generally within the first 2 months of therapy. Zileuton decreases the steady-state clearance of theophylline, substantially increasing its plasma concentrations. Zileuton also decreases warfarin clearance.

USE IN ASTHMA Most clinical trials with these drugs have studied patients with mild asthma who were not taking glucocorticoids. In general, the studies show a modest but significant improvement in pulmonary function and a decrease in symptoms and asthma exacerbations. For those who respond to antileukotriene therapy, the National Heart, Lung, and Blood Institute recognizes these drugs as alternatives to low-dose inhaled steroids for control of mild chronic asthma.

This class of drugs is not indicated for rapid bronchodilator therapy; thus, patients are instructed to have short-acting b adrenergic receptor agonists available as rescue medication. Montelukast and zafirlukast are effective with once- or twice-daily treatment, respectively. In contrast, zileuton is taken 4 times a day. Hepatic transaminases should be monitored in patients beginning zileuton therapy to guard against the potential of liver toxicity.

Anti-IgE Therapy

Omalizumab (xolair) is the first biological agent approved for the treatment of asthma. Omal-izumab is a recombinant humanized monoclonal antibody of the IgGlK subclass, targeted against IgE. IgE bound to omalizumab cannot bind to IgE receptors on mast cells and basophils, thereby preventing the allergic reaction at a very early step in the process (Figure 27-3).

PHARMACOKINETICS AND METABOLISM Omalizumab is delivered as a single subcutaneous injection every 2-4 weeks. It has a bioavailability of ~60%, reaching peak serum levels after 7-8 days. The serum elimination t1/2 is 26 days, with a clearance rate of ~2.5 mL/kg/day. The elimination of omalizumab-IgE complexes occurs in the liver reticuloendothelial system at a rate somewhat faster than that of free IgG. Some intact omalizumab is also excreted in the bile. There is little evidence of specific uptake of omalizumab by any tissue.

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