Effects of Concomitant Administration of Vonoprazan Fumarate on the Tacrolimus Blood Concentration in Kidney Transplant Recipients

Abstract

Vonoprazan fumarate (vonoprazan) is a new kind of acid suppressant with potent acid inhibitory effects. Therefore, it has been administered to kidney transplant recipients for treatment or prophylaxis of steroid ulcers, refractory peptic ulcers, and gastroesophageal reflux disease. Because tacrolimus, which is a well-established immunosuppressant for kidney transplantation, and vonoprazan share the CYP3A4 system for metabolism, drug interactions are anticipated upon simultaneous administration. We retrospectively analyzed 52 kidney transplant recipients who were converted from rabeprazole, which has a small effect on the tacrolimus trough blood concentration (C 0), to vonoprazan between August 2016 and July 2019. We compared the tacrolimus C 0 /tacrolimus dose (C 0 /D) before and after conversion and serum liver enzymes, serum total bilirubin, and the estimated glomerular filtration rate (eGFR). As a result, mean tacrolimus C 0 /D before and after conversion was 1.98 1.02 and 2.19 1.15 (ng/mL)/(mg/d), respectively, (p < 0.001). Additionally, mean aspartate transaminase (AST) before and after conversion was 18.6 4.2 and 19.6 5.2 IU/L, respectively, (p 0.037). Mean alanine transaminase (ALT) before and after conversion was 15.8 5.5 and 17.6 7.1 IU/L, respectively, (p 0.007). Mean eGFR before and after conversion was 50.6 14.4 and 51.4 14.7 mL/min/1.73 m 2 , respectively (p 0.021). Mean AST, ALT, and eGFR were slightly but significantly elevated within normal ranges after conversion. In conclusion, our study suggests that the mean tacrolimus C 0 /D was elevated significantly by converting from rabeprazole to vonoprazan, but it had little clinical significance. Vonoprazan can be administered safely to kidney transplant recipients receiving tacrolimus.

Drug–Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients

“…Therefore, vonopranan is considered to produce DDIs with tacrolimus in kidney transplant recipients under tacrolimus-based immunosuppressive therapy. A similar result has been reported in another study in which the C/D ratio of tacrolimus increased 1.1-fold after switching rabeprazole to vonoprazan in outpatients 2-7 years post-transplantation [27].…”

“…This may be a potential bias for the study setting. The increase in C/D ratio of tacrolimus after switching of rabeprazole to vonoprazan was large (41.8%) compared with previous studies by Mei T. [27] and Watari S. [30], which showed a 10.6% increase and no increase after the conversion, respectively, in the outpatient phase of posttransplantation. To confirm this difference, the data for a larger number of the patients is required in the early phase of post-transplantation.…”

Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms

“…A recently published retrospective cohort study in a single center (n = 52) showed that blood concentrations of tacrolimus increased with a statistical significance following conversion from rabeprazole to vonoprazan, but the change was ignorable [14]. They used tacrolimus trough concentration/tacrolimus dose (ng/mL)/(mg/day).…”

“…Rabeprazole is slightly metabolized by CYP2C19, whereas vonoprazan is hardly metabolized by CYP2C19 [14]. Patients in the CYP2C19 extensive and intermediate metabolizer subgroups are predicted to partially metabolize rabeprazole by CYP2C19 and thus should not have experienced significant antagonism on the CYP3A4 enzyme prior to conversion to vonoprazan.…”

Efficacy of Vonoprazan Fumarate Tablets in Refractory Reflux Esophagitis

“…It was found that CGRP expression was significantly increased in the esophageal mucosa of patients with CGRP and negatively correlated with patient's nociceptive threshold. Capsaicin receptors are highly expressed in the esophageal tissue of RRE patients and acid exposure stimulates the release of CGRP from esophageal nerve endings, thus increasing the sensitivity of the patient's esophageal mucosa to acid or mechanical stimuli [23] . Therefore, CGRP is closely related to visceral sensitivity in patients with RRE.…”