Zileuton adverse effects

Zileuton is a selective inhibitor of lipoxygenases (LOX), decreasing formation of all LTs. More rapid onset (1-3 h) and is adjunctive to steroids. Adverse effects include asthenia, headache, and t LFTs. 

Zileuton raises theophylline levels and increases the incidence of adverse effects. 

In a double-blind, crossover study, 13 healthy subjects were given 200 mg of theophylline Slo-Phyllin) four times daily for 5 days and either zileuton 800 mg twice daily or a placebo. Zileuton caused a 73% rise in the mean steady-state peak serum levels of theophylline (from 12 to 21 mg/L), a 92% increase in its AUC, and halved its apparent plasma clearance. During the use of zileuton the incidence of adverse effects increased (headache, gastrointestinal effects), which was attributed to theophylline toxicity, and this caused 3 of the original 16 subjects to withdraw from the study. ... 

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

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