Keywords
Drug-Drug Interaction
Immunosuppression
Calcineurin Inhibitors
Acid Suppressants
How to Cite
Abstract
Background: Tacrolimus is essential for immunosuppression in transplant recipients but presents risks of toxicity and rejection due to its narrow therapeutic window. Vonoprazan, increasingly replacing proton pump inhibitors (PPIs) in these patients, may alter tacrolimus blood levels, but its impact remains unclear.
Objective: To assess how switching from PPIs to vonoprazan affects tacrolimus through concentration and concentration-to-dose ratio, and to summarize related liver and kidney safety markers in transplant recipients.
Methods: A systematic review was conducted of four Japanese studies (140 kidney or liver transplant recipients) evaluating tacrolimus-based immunosuppression before and after conversion to vonoprazan. The synthesis used exploratory meta-analyses and narrative interpretation, with clinically meaningful changes prespecified, while emphasizing study limitations.
Results: Across studies, a trend toward higher tacrolimus levels was seen after switching to vonoprazan. However, the magnitude and consistency of these changes varied substantially between studies, and most results did not surpass thresholds for clinical concern. Liver and kidney safety signals were generally small and inconsistent. High risk of bias, considerable heterogeneity, and absence of pooled clinical endpoints prevent drawing firm conclusions from quantitative data. Pooled estimates are reported as exploratory only.
Conclusions: There is low-certainty evidence that vonoprazan may increase tacrolimus exposure in transplant recipients, but the clinical significance is unclear due to small, regionally focused studies with major methodological limitations. Therapeutic drug monitoring during and after conversion is prudent, and well-controlled trials in diverse populations are needed before definitive recommendations can be made.
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Copyright (c) 2025 Islam Rajab, Mohamed R. Ezz, Mohamed S. Elgendy, Omar K. Elsawy, Mohamed Wagdy, Mohamed A. Elshewikh, Abdallah Hussein, Patrick Tempera, Walid Baddoura