Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients
Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity,...
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2024-12-01
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| author | Alan D. Kaye Shivam S. Shah Coplen D. Johnson Adalyn S. De Witt Austin S. Thomassen Charles P. Daniel Shahab Ahmadzadeh Sridhar Tirumala Kristin Nicole Bembenick Adam M. Kaye Sahar Shekoohi |
| author_facet | Alan D. Kaye Shivam S. Shah Coplen D. Johnson Adalyn S. De Witt Austin S. Thomassen Charles P. Daniel Shahab Ahmadzadeh Sridhar Tirumala Kristin Nicole Bembenick Adam M. Kaye Sahar Shekoohi |
| author_sort | Alan D. Kaye |
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| description | Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias. Mycophenolate, a reversible inhibitor of inosine monophosphate dehydrogenase, frequently causes gastrointestinal disturbances, including diarrhea and colitis, as well as hematologic side effects like anemia and leukopenia, which increase infection risk. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as essential strategies for mitigating these toxicities. TDM ensures tacrolimus trough levels are maintained within a therapeutic range, minimizing the risks of nephrotoxicity and rejection. Pharmacogenomic insights, such as CYP3A5 polymorphisms, allow for personalized tacrolimus dosing based on individual metabolic profiles. For mycophenolate, monitoring inosine monophosphate dehydrogenase activity provides a pharmacodynamic approach to dose optimization, reducing gastrointestinal and hematologic toxicities. Emerging tools, including dried blood spot sampling and pharmacokinetic modeling, offer innovative methods to simplify monitoring and enhance precision in outpatient settings. Despite their utility, the toxicity profiles of these drugs, including those of early immunosuppressants such as cyclosporine and azathioprine, necessitate further consideration of alternative immunosuppressants like sirolimus, everolimus, and belatacept. Although promising, these newer agents require careful patient selection and further research. Future directions in immunosuppressive therapy include integrating individual pharmacogenetic data to refine dosing, minimize side effects, and improve long-term graft outcomes. This narrative review underscores the importance of personalized medicine and advanced monitoring in optimizing post-transplant care. |
| format | Article |
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| institution | Kabale University |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Current Issues in Molecular Biology |
| spelling | doaj-art-fae2e1af09b94720a0b175f2e1f3554d2025-01-24T13:27:21ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452024-12-01471210.3390/cimb47010002Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant PatientsAlan D. Kaye0Shivam S. Shah1Coplen D. Johnson2Adalyn S. De Witt3Austin S. Thomassen4Charles P. Daniel5Shahab Ahmadzadeh6Sridhar Tirumala7Kristin Nicole Bembenick8Adam M. Kaye9Sahar Shekoohi10Departments of Anesthesiology and Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USASchool of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USASchool of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USASchool of Medicine, Indiana University, 340 W 10th St., Indianapolis, IN 46202, USASchool of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USASchool of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USADepartment of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USADepartment of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USADepartment of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USADepartment of Pharmacy Practice, Thomas J. Long School of Pharmacy, University of the Pacific, 751 Brookside Road, Stockton, CA 95207, USADepartment of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USATacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias. Mycophenolate, a reversible inhibitor of inosine monophosphate dehydrogenase, frequently causes gastrointestinal disturbances, including diarrhea and colitis, as well as hematologic side effects like anemia and leukopenia, which increase infection risk. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as essential strategies for mitigating these toxicities. TDM ensures tacrolimus trough levels are maintained within a therapeutic range, minimizing the risks of nephrotoxicity and rejection. Pharmacogenomic insights, such as CYP3A5 polymorphisms, allow for personalized tacrolimus dosing based on individual metabolic profiles. For mycophenolate, monitoring inosine monophosphate dehydrogenase activity provides a pharmacodynamic approach to dose optimization, reducing gastrointestinal and hematologic toxicities. Emerging tools, including dried blood spot sampling and pharmacokinetic modeling, offer innovative methods to simplify monitoring and enhance precision in outpatient settings. Despite their utility, the toxicity profiles of these drugs, including those of early immunosuppressants such as cyclosporine and azathioprine, necessitate further consideration of alternative immunosuppressants like sirolimus, everolimus, and belatacept. Although promising, these newer agents require careful patient selection and further research. Future directions in immunosuppressive therapy include integrating individual pharmacogenetic data to refine dosing, minimize side effects, and improve long-term graft outcomes. This narrative review underscores the importance of personalized medicine and advanced monitoring in optimizing post-transplant care.https://www.mdpi.com/1467-3045/47/1/2tacrolimusmycophenolatepost-transplanttoxicityimmunosuppression |
| spellingShingle | Alan D. Kaye Shivam S. Shah Coplen D. Johnson Adalyn S. De Witt Austin S. Thomassen Charles P. Daniel Shahab Ahmadzadeh Sridhar Tirumala Kristin Nicole Bembenick Adam M. Kaye Sahar Shekoohi Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients Current Issues in Molecular Biology tacrolimus mycophenolate post-transplant toxicity immunosuppression |
| title | Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients |
| title_full | Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients |
| title_fullStr | Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients |
| title_full_unstemmed | Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients |
| title_short | Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients |
| title_sort | tacrolimus and mycophenolate mediated toxicity clinical considerations and options in management of post transplant patients |
| topic | tacrolimus mycophenolate post-transplant toxicity immunosuppression |
| url | https://www.mdpi.com/1467-3045/47/1/2 |
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