Major
Omeprazole × tacrolimus
Proton pump inhibitors×Calcineurin inhibitor (immunosuppressant)
Mechanism
Omeprazole blocks CYP2C19. In CYP2C19 slow metabolisers (genetic polymorphism), tacrolimus is predominantly metabolised by CYP2C19, and plasma levels may double.
Symptoms
Acute nephrotoxicity: rising creatinine, hypertension, tremor, headache. In transplant patients: accelerated graft function decline.
Management
In most patients, no clinically significant effect. In East Asian patients (high frequency of CYP2C19 slow metabolisers), alternative PPIs: pantoprazole or rabeprazole (weaker CYP2C19 effect). Check tacrolimus trough (C0) 1 week after starting omeprazole.