Importance of the Use of Omeprazole and Famotidine in the Development of Chronic Dysfunction of the Kidney Transplant

Background: Tacrolimus is metabolized in the liver with the participation of the CYP3A4 and CYP3A5 enzymes. Proton pump inhibitors are used in kidney transplant patients to prevent duodenal and gastric ulcer disease due to glucocorticoids. Omeprazole, unlike famotidine, is a substrate and inhibitor of the CYP2C19, CYP3A4, CYP3A5 enzymes. The aim of the study is to compare the effect of omeprazole and famotidine on the tacrolimus concentration and risk of developing chronic dysfunction of the kidney transplant. Methods: A randomized, non-blinded study was conducted in 24 adult patients with stable kidney transplant function who received a standard triple immunosuppression regimen. Patients were assigned to the study group (n=12) additionally receiving omeprazole (20 mg) or the control group (n=12) receiving famotidine (20 mg). At the time of qualification and during follow-up visits, tacrolimus blood concentration and selected laboratory tests were performed. Statistical analysis was performed using the MedCalc system. Results: A single administration of omeprazole increased tacrolimus concentrations. AUC0-6 amounted to 63.07±19.46 ng×h/mL (day 2) vs 54.23±10.48 ng×h/mL (day 1), (p=0.0295). Conversely, no significant changes were observed for famotidine. The value of creatinine concentration did not change significantly after three years in the study group (1.53±0.50 vs 1.70±0.72, p=0.5071) and in the control group (1.54±0.25 vs 1.50±0.49, p=0.1953). The difference in creatinine concentration values between the groups after three years was not significant (1.70±0.72 vs 1.50±0.49, p=0.6891). The value of tacrolimus concentration in the blood increased after a year in the study group (3.41±1.36 vs. 2.44±1.30, p=0.0101). A reduction in tacrolimus dosage was observed after three years in the study group (3.56±1.75 vs 2.78±1.00, p=0.0440) and in the control group (2.72±0.84 vs 2.10± 0.48, p=0.0051). In one patient in the study group and in the control group, the kidney transplant was rejected due to infection. Both patients are treated with hemodialysis. Conclusion: Omeprazole significantly increases blood exposure of tacrolimus after single administration and after one year from administration the drug. There was no effect of famotidine or omeprazole on the function of the kidney transplant. ClinicalTrials.gov identifier: NCT05061303.