Major
Esomeprazole × tacrolimus
Drugs for peptic ulcer and GORD. Proton pump inhibitors×Calcineurin inhibitor (immunosuppressant)
Mechanism
Esomeprazole inhibits CYP2C19. Tacrolimus is minimally metabolised by CYP2C19, but in patients with slow metabolism (CYP2C19 genetic polymorphism) this route becomes the main one. In such patients tacrolimus plasma levels rise.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. 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 esomeprazole.