Omeprazole × Tacrolimus

Tacrolimus is metabolised by CYP3A4 in the liver and gut wall (tacrolimus SmPC). The tacrolimus SmPC classes omeprazole as a moderate or weak CYP3A4 inhibitor that can raise tacrolimus trough blood concentrations, sometimes rapidly. The omeprazole SmPC also reports higher tacrolimus concentrations with omeprazole but lists the mechanism as unknown.

Signs of tacrolimus excess: tremor, tingling in the limbs, headache, changes in mental status, rising creatinine and potassium. QT prolongation on the electrocardiogram is possible, with a risk of dangerous arrhythmia.

The combination is acceptable with monitoring. From the first days of co-administration, check tacrolimus trough blood concentrations frequently and reduce the dose if needed; closely monitor renal function, the QT interval on the electrocardiogram (ECG) and other adverse effects (tacrolimus SmPC). The omeprazole SmPC also advises closer monitoring of tacrolimus concentrations and renal function (creatinine clearance), with tacrolimus dose adjustment if needed (omeprazole SmPC). The US Food and Drug Administration (FDA) gives the same approach: monitor trough concentrations and reduce the dose if needed (US tacrolimus label).