Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for <i><scp>C</scp>lostridium difficile</i>

Early, Caitlin R.; Park, Jeong Mi; Dorsch, Michael P.; Pogue, Kristen; Hanigan, Sarah

doi:10.1111/tid.12588

Cited by 5 publications

(2 citation statements)

References 10 publications

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“…Because the observed changes in dose‐normalized TAC concentrations were calculated in ratios, we transformed the dose‐normalized TAC concentrations to the logarithmic scale by calculating the natural log of the data. Tacrolimus concentration divided by dose (C/D) is a method used in solid organ transplant literature to determine the rate of tacrolimus metabolism . As the primary outcome was a continuous variable comparing two non‐paired groups, a t test was performed.…”

Section: Methodssupporting

confidence: 91%

“…Tacrolimus concentration divided by dose (C/D) is a method used in solid organ transplant literature to determine the rate of tacrolimus metabolism. 21,[23][24][25][26] As the primary outcome was a continuous variable comparing two non-paired groups, a t test was performed. All other statistical analyses were performed using descriptive statistics.…”

Section: Discussionmentioning

confidence: 99%

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Impact of direct‐acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients

Bixby

Fitzgerald

Leek

et al. 2019

Transplant Infectious Dis

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Introduction Direct‐acting antivirals (DAAs) have transformed hepatitis C virus (HCV) management post‐liver transplant. As HCV clears during DAA treatment, hepatic metabolism improves, resulting in decreased tacrolimus concentrations that may require dose adjustment. The purpose of this study was to determine appropriate management of immunosuppression in liver transplant recipients during and following treatment of HCV. Methods This study was a single‐center retrospective analysis of 71 liver transplant recipients who were treated for HCV with DAAs. The primary outcome was change in dose‐normalized tacrolimus concentrations from the start of DAA treatment to 12 weeks following therapy. Results The mean change in log‐transformed dose‐normalized tacrolimus concentrations was a reduction of 0.43 ng/mL/mg (95% CI; 0.26‐0.60, P < 0.0001). The greatest decrease occurred in the first 4 weeks of treatment, after which levels stabilized. The overall mean tacrolimus concentration was 4.8 ng/mL (±2.5). Two patients (3%) developed acute cellular rejection and two patients (3%) had graft loss and died. Conclusion From the start of treatment to 12 weeks post‐DAA therapy, liver transplant recipients experienced a significant decrease in dose‐normalized tacrolimus concentrations. In conclusion, close monitoring of tacrolimus concentrations is warranted during and following treatment with DAAs, as dose increases may be indicated in order to maintain therapeutic concentrations to prevent graft rejection.

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Section: Methodssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Impact of direct‐acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients

Bixby

Fitzgerald

Leek

et al. 2019

Transplant Infectious Dis

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Prevention and Treatment of Clostridium difficile-Associated Diarrhea in Solid Organ Transplant Recipients

Pouch

2018

Infectious Disease Clinics of North America

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Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation

Mohamed,

Saqr,

Staley

et al. 2024

Transplantation

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The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug–microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.

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Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile

Abstract: CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment.

Cited by 5 publications

References 10 publications

Impact of direct‐acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients

Impact of direct‐acting antivirals for hepatitis C virus therapy on tacrolimus dosing in liver transplant recipients

Prevention and Treatment of Clostridium difficile-Associated Diarrhea in Solid Organ Transplant Recipients

Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation

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