Erythromycin × Tacrolimus

Erythromycin inhibits CYP3A4 and P-glycoprotein (erythromycin SmPC). CYP3A4 breaks down tacrolimus, and the tacrolimus SmPC places erythromycin in the same group as strong CYP3A4 inhibitors: tacrolimus levels can rise sharply within 1–3 days, and overall exposure can increase more than 5-fold. The effect can last several days after co-administration ends (tacrolimus SmPC). Both drugs can prolong the QT interval (both SmPCs).

Signs of tacrolimus excess: rising creatinine and worse kidney function, tremor, headache and other signs of neurotoxicity. QT prolongation on the ECG with a risk of torsades de pointes (both SmPCs).

The erythromycin SmPC does not recommend giving it with tacrolimus, and the tacrolimus SmPC advises avoiding the combination. If erythromycin cannot be avoided, treatment is managed by a transplant specialist. Consider skipping the tacrolimus dose on the day erythromycin starts and restart the next day at a reduced dose guided by blood levels. Measure tacrolimus trough levels at baseline, check them often from the first days of co-treatment and reassess after erythromycin is stopped, adjusting the dose to these values. Monitor kidney and graft function, the QT interval on the ECG and signs of neurotoxicity closely (tacrolimus SmPC). Erythromycin is contraindicated with a history of QT prolongation or ventricular arrhythmia and with low potassium or magnesium (erythromycin SmPC). The tacrolimus SmPC classes azithromycin as a moderate or weak CYP3A4 inhibitor: it can also raise tacrolimus levels and needs the same monitoring.