Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 2C8 and/or 2C9 may increase the plasma concentrations of montelukast, which is metabolized by these isoenzymes in addition to CYP450 3A4. When montelukast was administered with the potent CYP450 2C8/2C9 inhibitor gemfibrozil, montelukast systemic exposure (AUC) increased by 4.4-fold. The addition of itraconazole, a potent CYP450 3A4 inhibitor, to gemfibrozil and montelukast did not further increase the AUC of montelukast. Administration of itraconazole alone with montelukast also resulted in no significant increase in the AUC of montelukast, which would suggest that montelukast is primarily metabolized by CYP450 2C8 and 2C9 in vivo.

MANAGEMENT: According to the product labeling, no dosage adjustment of montelukast is required when used in combination with gemfibrozil. However, it may be advisable to monitor patients for potentially increased adverse effects during coadministration with gemfibrozil or other CYP450 2C8/2C9 inhibitors.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.