Question 10. How safe are the anti-leukotrienes?

From Chapter 6 of the Philippine Consensus Report on Asthma 2004 by the Philippine College of Chest Physicians.
This guideline starts below.

How safe are the anti-leukotrienes?

Answer

Anti-leukotrienes (anti-LTs) are safe drugs even for prolonged use.

Summary of Evidence

The Antileukotriene Working Group has clearly established the safety of anti-LTs even when given for prolonged periods of time. An analysis of four 13-week RCTs of similar methodology assessing efficacy and safety of anti-LTs showed that of the 1484 asthmatics, 560 or 64% in the zafirlukast group and 391 (65%) in the placebo group developed adverse effects. In one of these studies, extended by Grossman to 39 more weeks, the most common adverse events noted were pharyngitis (zafirlukast and placebo 24.2%) and headache (zafirlukast, 13%; placebo 10.9%). A similar study assessing safety and tolerability of montelukast reported the same frequency of adverse reactions.

Anti-LTs should be used with caution among patients with liver disease, although more recent studies failed to implicate direct hepatotoxicity with leukotriene receptor antagonist use. Churg-Strauss syndrome, a rare severe eosinophilic granulomatous lung disease, has been reported to be associated with anti-LT use (1:20,000 asthma cases), noted particularly during the period of oral steroid tapering. It was proposed that this situation may be due to the unmasking, rather than causation, of Churg-Strauss syndrome. The syndrome may have mistakenly diagnosed as asthma and initially controlled with oral steroids. Once the oral steroid dose has decreased during tapering, then the syndrome resurfaced.