Drug Interaction Report

GENERALLY AVOID: Based on in vitro inhibition data, coadministration with dalfopristin-quinupristin may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme, including certain agents that can cause prolongation of the QTc interval (e.g., cisapride, disopyramide, pimozide, quinidine, tacrolimus). High plasma levels of these agents have been rarely associated with ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes, as well as cardiac arrest and sudden death.

MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of agents that may prolong the QTc interval, concomitant use with dalfopristin-quinupristin should be avoided if they are known to be substrates of CYP450 3A4.

CONTRAINDICATED: The consumption of grapefruit juice has been associated with significantly increased plasma concentrations of terfenadine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. Terfenadine in high serum levels has been associated with prolongation of the QT interval and development of torsade de pointes, a potentially fatal ventricular arrhythmia.

MANAGEMENT: Due to the risk of cardiotoxicity, patients receiving the drug should be advised to avoid consumption of grapefruit products. Loratadine, cetirizine, and fexofenadine may be safer alternatives in patients who may have trouble adhering to the dietary restriction.