Zafirlukast Terfenadine

The plasma concentrations of zafirlukast are reduced when it is administered concurrently with terfenadine (7). 

Zafirlukast plasma levels are decreased by terfenadine but the clinical significance of this is unciear. Zafiriukast does not increase the ieveis of terfenadine, and concurrent use does not proiong the QTc intervai. 

A study in 16 healthy men given zafirlukast 160 mg twice daily for 16 days with terfenadine 60 mg twice daily on days 8 to 16 found that the mean maximum serum levels and AUC of zafirlukast were reduced by 70% and 60%, respectively. There was a small, non-significant reduction in the terfenadine AUC and serum levels. A study in 8 healthy subjects given zafirlukast 160 mg twice daily with terfenadine 60 mg twice daily for 8 days found that the AUC of terfenadine and the QTc interval were not significantly increased with concurrent use, despite the fact that zafirlukast appears to inhibit CYP3A4 in vitro, the major enzyme involved in terfenadine metabolism. The reduction in zafirlukast serum levels would be expected to reduce its antiasthmatic effects, but this needs assessment. If both drugs are given be alert for a reduced response to zafirlukast. 

Suttle AB, Birmingham BK, Vargo DL, Wilkmson LA, Morganroth J. Pharmacokinetics of zafirlukast and terfenadine after coadministration to healthy meii J Clin Pharmacol (1997) 37, 870. 

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