Why can systemic ketoconazole increase the risk of palpitations and QTc prolongation with Seretide Accuhaler?

Systemic ketoconazole significantly increases systemic exposure to salmeterol in Seretide Accuhaler, potentially increasing palpitations and QTc prolongation; concomitant treatment should be avoided unless benefits outweigh the potentially increased risk of systemic salmeterol side effects.