Dronedarone × Tacrolimus

Dronedarone is a moderate CYP3A4 inhibitor and a potent P-glycoprotein inhibitor (dronedarone label). Tacrolimus is metabolized mainly by CYP3A4 in the liver and gut wall, so its blood levels can rise with dronedarone (tacrolimus and dronedarone labels). The second mechanism is electrical: dronedarone moderately prolongs the QT interval, and tacrolimus can itself prolong QT and cause torsades de pointes (labels of both drugs).

Signs of tacrolimus excess: worsening kidney function with rising creatinine, tremor, headache, and raised blood pressure, blood glucose and potassium (tacrolimus label). The combination prolongs the QT interval on the ECG; marked prolongation can lead to torsades de pointes with palpitations, dizziness and fainting (tacrolimus and dronedarone labels).

Give CYP3A4 inhibitors with tacrolimus only after consulting a transplant specialist (tacrolimus label). Measure tacrolimus blood levels often from the first days of co-administration and adjust the dose (tacrolimus and dronedarone labels). For CYP3A4 inhibitors that also prolong the QT interval, the FDA tacrolimus label recommends a lower tacrolimus dose, frequent level checks and QT monitoring. Monitor kidney function and the ECG closely during the combination (tacrolimus label). Correct low potassium and magnesium before and during dronedarone treatment, and stop dronedarone if QTc reaches 500 ms or more (dronedarone label).