THERAPEUTIC DOSAGE RANGES AND CHRONIC ADVERSE EFFECTS OF TACROLIMUS IN THAI KIDNEY TRANSPLANT PATIENTS
DOI:
https://doi.org/10.22159/ijap.2021.v13s1.Y0053Keywords:
Therapeutic dosage ranges, Chronic adverse effects, Tacrolimus, Kidney transplant patientsAbstract
Objective: This study proposed to study the therapeutic dosage ranges and to determine the prevalence of and the risk factors for the adverse effects
of Thai tacrolimus-based therapy kidney transplant patients.
Methods: The fifty-nine kidney transplant patients who had kidney transplantation between January 2016 and May 2018 and were non-diabetic,
non-hypertension, and normal kidney parameters before kidney transplantation were enrolled and followed up for 6 months. Data on graft rejection
episodes and three significant adverse effects of tacrolimus, nephrotoxicity, hypertension (HTN), and post-transplant diabetes mellitus (PTDM) at
each time point were recorded and analyzed.
Results: The range and mean (±standard deviation) of tacrolimus troughs level for the 204 points were 3.9–10.2 ng/ml and 6.4±1.8 ng/ml, respectively.
About 73% of patients had HTN, 61% were on antihypertensive drugs, and 32% had PTDM. Seven patients (12%) proved to have allograft rejection
by kidney biopsy. Only four patients did not have any three adverse effects. Similarly, laboratory parameters (SCr, BUN, and blood pressure) were
identical during each period. All patients received prednisolone and mycophenolate mofetil as part of the comedication immunosuppressive regimen.
Conclusion: There was no significant difference between tacrolimus chronic adverse effects and therapeutic tacrolimus trough concentrations in Thai
kidney transplant patients. Further investigations concerning pharmacokinetics and pharmacodynamics will be needed to improve the efficacy and
safety of tacrolimus.
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References
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transplantation patients and healthy volunteers by flow cytometric
analysis. Asia Pac J Sci Technol 2019;24:14456.
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Acute rejection episodes after kidney transplantation. Saudi J Kidney
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10. Marcen R, Morales JM, del Castillo D, Campistol JM, Seron D,
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Tacrolimus-induced alopecia in female kidney-pancreas transplant
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A new side effect of immunosuppression: High incidence of hearing
impairment after liver transplantation. Liver Transpl 2006;12:411-5.
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Lotufo RF. Incidence of tacrolimus-induced gingival overgrowth in
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trough level increases risk of acute rejection in kidney transplant
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Pfaff WW, et al. The changing causes of graft loss and death after
kidney transplantation. Transplantation 2002;73:1923-8.
22. Margreiter R, Pohanka E, Sparacino V, Sperschneider H, Kunzendorf U,
Huber W, et al. Open prospective multicenter study of conversion to
tacrolimus therapy in renal transplant patients experiencing ciclosporinrelated
side-effects. Transpl Int 2005;18:816-23.
23. Margreiter R, European Tacrolimus vs Ciclosporin Microemulsion
Renal Transplantation Study G. Efficacy and safety of tacrolimus
compared with ciclosporin microemulsion in renal transplantation: A
randomised multicentre study. Lancet 2002;359:741-6.
24. Loinaz C, Marin LM, Gonzalez-Pinto I, Gomez R, Jimenez C,
Moreno E. A single-centre experience with cyclosporine microemulsion
versus tacrolimus in 100 randomized liver transplant recipients:
Midterm efficacy and safety. Transpl Proc 2001;33:3439-41.
25. Zhang Y, Moran AE. Trends in the prevalence, awareness, treatment,
and control of hypertension among young adults in the United States,
1999 to 2014. Hypertension 2017;70:736-42.
26. Kamar N, Mariat C, Delahousse M, Lefrancois N, Dantal J,
Benhamou P. New onset diabetes mellitus incidence and risk factors
in kidney transplantation: Results of the observational cross-sectional
study diapason. Transpl Proc 2006;38:2295-7.
27. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after
kidney transplantation in the United States. Am J Transpl 2003;3:178-85.
28. Aekplakorn W, Chariyalertsak S, Kessomboon P, Sangthong R,
Inthawong R, Putwatana P, et al. Prevalence and management of
diabetes and metabolic risk factors in Thai adults: The Thai national
health examination survey IV, 2009. Diabetes Care 2011;34:1980-5.
29. Groetzner J, Meiser BM, Schirmer J, Koglin J, vScheidt W, Klauss V,
et al. Tacrolimus or cyclosporine for immunosuppression after cardiac
transplantation: Which treatment reveals more side effects during longterm
follow-up? Transpl Proc 2001;33:1461-4.
et al. Dialysis requirement and long-term major adverse cardiovascular
events in patients with chronic kidney disease and superimposed acute
kidney injury. Nephron 2017;136:95-102.
2. Katzung B, Knuidering-Hall M, Trevor A. Katzung and Trevor’s
Pharmacology Examination and Board Review. 11th ed. New York:
McGraw-Hill Education; 2015.
3. Klaasen RA, Bergan S, Bremer S, Daleq L, Andersen AM, Midtvedt K,
et al. Longitudinal study of tacrolimus in lymphocytes during the first
year after kidney transplantation. Ther Drug Monit 2018;40:558-66.
4. Fukuhara N, Ono Y, Hattori R, Nishiyama N, Yamada S, Kamihira O,
et al. The long-term outcome of tacrolimus in cadaveric kidney
transplantation from non-heart beating donors. Clin Transplant
2005;19:153-7.
5. Anutrakulchai S, Pongskul C, Kritmetapak K, Limwattananon C,
Vannaprasaht S. Therapeutic concentration achievement and allograft
survival comparing usage of conventional tacrolimus doses and
CYP3A5 genotype-guided doses in renal transplantation patients. Br J
Clin Pharmacol 2019;85:1964-73.
6. Filler G. Finding the optimal therapeutic window for tacrolimus.
Pediatr Transplant 2014;18:783-5.
7. Boonsom S, Vannaprasaht S, Tassaneeyakul W, Wongratanacheewin S,
Kaewraemruaen C. Long term stability of immunophenotypic T
cell subsets from whole blood of tacrolimus-based therapy kidney
transplantation patients and healthy volunteers by flow cytometric
analysis. Asia Pac J Sci Technol 2019;24:14456.
8. Hamida FB, Barbouch S, Bardi R, Helal I, Kaaroud H, Fatma LB, et al.
Acute rejection episodes after kidney transplantation. Saudi J Kidney
Dis Transpl 2009;20:370-4.
9. Pascual J, Ortuno J, Spanish, Italian Tacrolimus Study G. Simple
tacrolimus-based immunosuppressive regimens following renal
transplantation: A large multicenter comparison between double and
triple therapy. Transpl Proc 2002;34:89-91.
10. Marcen R, Morales JM, del Castillo D, Campistol JM, Seron D,
Valdes F, et al. Posttransplant diabetes mellitus in renal allograft
recipients: A prospective multicenter study at 2 years. Transpl Proc
2006;38:3530-2.
11. Numakura K, Satoh S, Tsuchiya N, Horikawa Y, Inoue T, Kakinuma H,
et al. Clinical and genetic risk factors for posttransplant diabetes
mellitus in adult renal transplant recipients treated with tacrolimus.
Transplantation 2005;80:1419-24.
12. Tricot L, Lebbe C, Pillebout E, Martinez F, Legendre C, Thervet E.
Tacrolimus-induced alopecia in female kidney-pancreas transplant
recipients. Transplantation 2005;80:1546-9.
13. Caillard S, Agodoa LY, Bohen EM, Abbott KC. Myeloma, hodgkin
disease, and lymphoid leukemia after renal transplantation:
Characteristics, risk factors and prognosis. Transplantation
2006;81:888-95.
14. Rifai K, Kirchner GI, Bahr MJ, Cantz T, Rosenau J, Nashan B, et al.
A new side effect of immunosuppression: High incidence of hearing
impairment after liver transplantation. Liver Transpl 2006;12:411-5.
15. Sekiguchi RT, Paixao CG, Saraiva L, Romito GA, Pannuti CM,
Lotufo RF. Incidence of tacrolimus-induced gingival overgrowth in
the absence of calcium channel blockers: A short-term study. J Clin
Periodontol 2007;34:545-50.
16. Sperschneider H, European Renal Transplantation Study G. A large,
multicentre trial to compare the efficacy and safety of tacrolimus with
cyclosporine microemulsion following renal transplantation. Transpl
Proc 2001;33:1279-81.
17. Jensik SC. Tacrolimus (FK 506) in kidney transplantation: Three-year
survival results of the US multicenter, randomized, comparative trial.
FK 506 kidney transplant study group. Transpl Proc 1998;30:1216-8.
18. Arreola-Guerra JM, Serrano M, Morales-Buenrostro LE, Vilatoba M,
Alberu J. Tacrolimus trough levels as a risk factor for acute rejection in
renal transplant patients. Ann Transplant 2016;21:105-14.
19. Huang CT, Shu KH, Ho HC, Wu MJ. Higher variability of tacrolimus
trough level increases risk of acute rejection in kidney transplant
recipients. Transpl Proc 2016;48:1978-80.
20. Leblanc J, Subrt P, Pare M, Hartell D, Senecal L, Blydt-Hansen T,
et al. Practice patterns in the treatment and monitoring of acute t cellmediated
kidney graft rejection in Canada. Can J Kidney Health Dis
2018;5:1-12.
21. Howard RJ, Patton PR, Reed AI, Hemming AW, Van der Werf WJ,
Pfaff WW, et al. The changing causes of graft loss and death after
kidney transplantation. Transplantation 2002;73:1923-8.
22. Margreiter R, Pohanka E, Sparacino V, Sperschneider H, Kunzendorf U,
Huber W, et al. Open prospective multicenter study of conversion to
tacrolimus therapy in renal transplant patients experiencing ciclosporinrelated
side-effects. Transpl Int 2005;18:816-23.
23. Margreiter R, European Tacrolimus vs Ciclosporin Microemulsion
Renal Transplantation Study G. Efficacy and safety of tacrolimus
compared with ciclosporin microemulsion in renal transplantation: A
randomised multicentre study. Lancet 2002;359:741-6.
24. Loinaz C, Marin LM, Gonzalez-Pinto I, Gomez R, Jimenez C,
Moreno E. A single-centre experience with cyclosporine microemulsion
versus tacrolimus in 100 randomized liver transplant recipients:
Midterm efficacy and safety. Transpl Proc 2001;33:3439-41.
25. Zhang Y, Moran AE. Trends in the prevalence, awareness, treatment,
and control of hypertension among young adults in the United States,
1999 to 2014. Hypertension 2017;70:736-42.
26. Kamar N, Mariat C, Delahousse M, Lefrancois N, Dantal J,
Benhamou P. New onset diabetes mellitus incidence and risk factors
in kidney transplantation: Results of the observational cross-sectional
study diapason. Transpl Proc 2006;38:2295-7.
27. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after
kidney transplantation in the United States. Am J Transpl 2003;3:178-85.
28. Aekplakorn W, Chariyalertsak S, Kessomboon P, Sangthong R,
Inthawong R, Putwatana P, et al. Prevalence and management of
diabetes and metabolic risk factors in Thai adults: The Thai national
health examination survey IV, 2009. Diabetes Care 2011;34:1980-5.
29. Groetzner J, Meiser BM, Schirmer J, Koglin J, vScheidt W, Klauss V,
et al. Tacrolimus or cyclosporine for immunosuppression after cardiac
transplantation: Which treatment reveals more side effects during longterm
follow-up? Transpl Proc 2001;33:1461-4.
Published
31-01-2021
How to Cite
BOONSOM, S., VANNAPRASAHT, S., & PREECHAGOON, Y. (2021). THERAPEUTIC DOSAGE RANGES AND CHRONIC ADVERSE EFFECTS OF TACROLIMUS IN THAI KIDNEY TRANSPLANT PATIENTS. International Journal of Applied Pharmaceutics, 13(1), 13–16. https://doi.org/10.22159/ijap.2021.v13s1.Y0053
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