Lack of Clinically Relevant Interaction Between Desloratadine and Erythromycin

Abstract

Objective: To evaluate the bioavailability, cardiac safety and tolerability of desloratadine when given in combination with the CYP3A4 inhibitor erythromycin.

Design: A randomised, 2-way crossover, placebo-controlled, third party-blind, multiple dose study.

Participants: 24 healthy volunteers (12 men, 12 women) aged 19 to 46 years.

Interventions: Oral desloratadine 7.5mg daily in combination with either placebo (n = 24) or erythromycin 500mg every 8 hours (n = 24) for 10 days. After a minimum 7-day washout period, participants crossed over to the alternative regimen.

Main outcome measures: ECG parameters.

Results: Desloratadine/erythromycin did not induce clinically or statistically significant changes in any ECG parameter. The maximum corrected QT (QT_C) interval was 445 msec for both treatments. The peak plasma concentration and area under the plasma concentration-time curve from 0 to 24 hours of desloratadine were slightly increased by 1.2- and 1.1-fold by concomitant administration of erythromycin compared with desloratadine/placebo. Gastrointestinal adverse events were more frequent after desloratadine/erythromycin than desloratadine/placebo (46 s 4%), reflecting the poor gastrointestinal tolerability of erythromycin. There were no reports of syncope.

Conclusion: Combined desloratadine/erythromycin therapy was well tolerated and had no clinically relevant electrocardiographic effects at a dose that was 50% higher than the recommended dose of 5mg. Although coadministration of erythromycin slightly increased plasma concentrations of desloratadine, this change did not correlate with any prolongation of the QT_C interval, and no toxicity was observed clinically.