Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QTc prolongation

Abstract

In healthy men and women, concomitant nefazodone treatment at a therapeutic dose increases exposure to both terfenadine and carboxyterfenadine. This increased exposure is associated with marked QTc prolongation, which is correlated with terfenadine plasma concentration. A similar interaction occurs with loratadine, although it is of lesser magnitude. Concomitant administration of nefazodone with terfenadine may have predisposed individuals to the arrhythmia associated with QTc prolongation, torsade de pointes, when terfenadine was available for clinical use. However, a new finding is that in the context of higher than clinically recommended daily doses (20 mg) of loratadine concomitant administration with a metabolic inhibitor such as nefazodone can also result in QTc prolongation.