We aimed to present a drug monitoring profile of tacrolimus and proton pump inhibitor coadministration in a 23-year-old male patient with a history of high blood pressure who underwent kidney transplant. The patient’s serum trough levels of tacrolimus were in the therapeutic range until omeprazole 20 mg daily was prescribed. Tacrolimus trough serum level increased to 29.5 ng/mL under the same daily dose and to 13.9 ng/mL after tacrolimus daily dose was decreased to 6 mg/day. This increase in tacrolimus serum level was behind a renal function alteration. After withdrawal of omeprazole, tacrolimus trough serum level returned to the therapeutic range. Because interactions between tacrolimus and omeprazole could result in toxicities, careful monitoring of tacrolimus serum levels should be considered to adjust the dosage.

Key words : Immunosuppression, Kidney function, Omeprazole, Renal transplant

Introduction
Tacrolimus is an effective immunosuppressant drug used to prevent solid-organ transplant rejection. Similar to others targets of hepatic CYP3A4/5 enzyme systems metabolism, tacrolimus is susceptible to many clinically significant drug interactions.¹ Herein, we aimed to present a drug monitoring profile of tacrolimus and proton pump inhibitor coadministration in a kidney transplant recipient.

Case Report
A 23-year-old male patient with a history of high blood pressure underwent a kidney transplant. Tacrolimus, mycophenolate, and prednisone were prescribed for immunosuppression. Tacrolimus trough serum levels were monitored routinely posttransplant, with a chronic therapeutic range target of between 4 and 12 ng/mL.² The patient’s serum trough levels of tacrolimus ranged between 6 and 9.8 ng/mL under a 10-mg daily dose of tacrolimus. For acid blockade, omeprazole at a dose of 20 mg daily was prescribed for our patient 8 months posttransplant. After omeprazole administration, tacrolimus trough serum level increased to 29.5 ng/mL under the same daily dose and to 13.9 ng/mL after tacrolimus daily dose was decreased to 6 mg/day. This increase in tacrolimus serum level was behind a renal function alteration. In fact, the patient’s creatinine plasma level increased from 104 μmol/mL to 174 μmol/mL. Omeprazole was withdrawn, and, a few weeks later, tacrolimus trough serum level returned to the therapeutic range (between 5.3 and 8.9 ng/mL) (Figure 1).

Discussion
Omeprazole is the widely prescribed proton pump inhibitor for treatment and prevention of acid-related disorders in renal transplant recipients.³ However, omeprazole is known for numerous pharmacokinetic drug interactions involving cytochrome P450, more precisely the CYP2C19 isoenzyme. In vitro, omeprazole is tacrolimus’s metabolism inhibitor in human liver microsomes.⁴ To our knowledge, no clinical trials have been published about the relevance of such an interaction among transplant patients.

We suggest that interactions between tacrolimus and omeprazole could result in toxicities. Thus, careful monitoring of tacrolimus serum levels should be considered. Based on this case report, we emphasize the importance of personalized medicine in patients who have undergone organ transplant and for whom immunosuppressant medication is a milestone during their treatment journey.

References:

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