Abstract

Research Article

Comparative study of once daily tacrolimus (extended-release capsule) versus conventional twice daily tacrolimus in renal transplant recipients

Sanjay Srinivasa*

Published: 15 November, 2022 | Volume 6 - Issue 2 | Pages: 050-054

Background: One of the common causes of chronic allograft nephropathy is nonadherence to medications, contributing to 30% of graft loss in the developed world. The non-adherence is attributed predominantly to pill burden.
Once-daily dosing of tacrolimus instead of conventional twice-daily dosing may enhance adherence to medication and improve long-term outcomes. The present study is a retrospective analysis comparing the safety and effectiveness of De Novo (use from day 1) once daily (OD) Tacrolimus (extended-release capsules) to conventional twice-a-day (BD) tacrolimus, in renal transplant recipients operated at Suguna Hospital Bangalore India. 
Material and Methods: Records of 24 Transplant patients on De novo OD Tacrolimus were analyzed and compared retrospectively to 24 transplant patients treated De Novo with conventional BD tacrolimus on a regular follow-up for at least 2 yrs. post-transplant at our center. 
Results: Various parameters recorded till the last follow-up were analyzed and compared. The average weight of the cohort (64.6 kg vs. 66.6 kg), average tacrolimus dose (2.7 mg vs. 2.15 mg), average Tac dose/kg body weight (0.04 mg vs. 0.03 mg), average Sr.Creatinine, at Last, Follow up (1.2 mg/dl vs. 1.32 mg/dl) were comparable in both groups and were statistically insignificant (p > 0.05). However, there was a higher incidence of Post-Transplant Diabetes Mellitus (PTDM) noted in the Conventional BD Tacrolimus group (20.83%) compared to the OD Tacrolimus group (4.1%) and it was statistically significant (p = 0.17). The Infection rate of 41.67% in the conventional BD Tacrolimus group was much higher compared to the OD Tacrolimus group (4.17%) which was statistically significant (p = 0.01). There was 100% patient and graft survival at the end of two years in both groups. Tacrolimus Dose for OD and Conventional BD dosing were similar, unlike earlier studies recommending a 10% increase in dose for OD tacrolimus compared to BD dosing.
Conclusion: OD Tacrolimus dose is comparable to conventional BD dose Tacrolimus in its safety and Efficacy; however, it scores over conventional BD dose Tacrolimus in terms of post-transplant infections and post-transplant diabetes mellitus (PTDM) and a more stable serum trough level. 

Read Full Article HTML DOI: 10.29328/journal.ijcv.1001050 Cite this Article Read Full Article PDF

Keywords:

OD Tacrolimus; Post-renal transplant; Immunosuppressant

References

  1. Spencer CM, Goa KL, Gillis JC. Tacrolimus. An update of its pharmacology and clinical efficacy in the management of organ transplantation. Drugs. 1997 Dec;54(6):925-75. doi: 10.2165/00003495-199754060-00009. PMID: 9421697.
  2. Banas B, Krämer BK, Krüger B, Kamar N, Undre N. Long-Term Kidney Transplant Outcomes: Role of Prolonged-Release Tacrolimus. Transplant Proc. 2020 Jan-Feb;52(1):102-110. doi: 10.1016/j.transproceed.2019.11.003. Epub 2019 Dec 31. PMID: 31901329.
  3. Posadas Salas MA, Srinivas TR. Update on the clinical utility of once-daily tacrolimus in the management of transplantation. Drug Des Devel Ther. 2014 Sep 1;8:1183-94. doi: 10.2147/DDDT.S55458. PMID: 25210441; PMCID: PMC4155987.
  4. Mathew BS, Fleming DH, Jeyaseelan V, Chandy SJ, Annapandian VM, Subbanna PK, John GT. A limited sampling strategy for tacrolimus in renal transplant patients. Br J Clin Pharmacol. 2008 Oct;66(4):467-72. doi: 10.1111/j.1365-2125.2008.03251.x. Epub 2008 Jun 28. PMID: 18662286; PMCID: PMC2561121.
  5. Summary of Product Characteristics of OD 0.5 mg, 1 mg, 3 mg and 5 mg prolonged-release hard capsules; Astellas Pharma Ltd; June 2015. Available from: https://www.medicines.org.uk/emc/medicine/19814
  6. Sukkha S, Suansanae T, Iamrahong P, Wiwattanathum P. Trough Level and Tacrolimus Variability of Early Converted Once-Daily Tacrolimus: 1-Year Follow-up Study. Transplant Proc. 2020 Apr;52(3):775-779. doi: 10.1016/j.transproceed.2019.12.039. Epub 2020 Mar 4. PMID: 32143870.
  7. Musuamba FT, Mourad M, Haufroid V, Delattre IK, Verbeeck RK, Wallemacq P. Time of drug administration, CYP3A5 and ABCB1 genotypes, and analytical method influence tacrolimus pharmacokinetics: a population pharmacokinetic study. Ther Drug Monit. 2009 Dec;31(6):734-42. doi: 10.1097/FTD.0b013e3181bf8623. PMID: 19855314.
  8. Miura M, Satoh S, Niioka T, Kagaya H, Saito M, Hayakari M, Habuchi T, Suzuki T. Early phase limited sampling strategy characterizing tacrolimus and mycophenolic acid pharmacokinetics adapted to the maintenance phase of renal transplant patients. Ther Drug Monit. 2009 Aug;31(4):467-74. doi: 10.1097/FTD.0b013e3181ae44b9. PMID: 19571775.
  9. Miura M, Satoh S, Niioka T, Kagaya H, Saito M, Hayakari M, Habuchi T, Suzuki T. Early phase limited sampling strategy characterizing tacrolimus and mycophenolic acid pharmacokinetics adapted to the maintenance phase of renal transplant patients. Ther Drug Monit. 2009 Aug;31(4):467-74. doi: 10.1097/FTD.0b013e3181ae44b9. PMID: 19571775.
  10. Laederach-Hofmann K, Bunzel B. Noncompliance in organ transplant recipients: a literature review. Gen Hosp Psychiatry. 2000 Nov-Dec;22(6):412-24. doi: 10.1016/s0163-8343(00)00098-0. PMID: 11072057.
  11. Denhaerynck K, Dobbels F, Cleemput I, Desmyttere A, Schäfer-Keller P, Schaub S, De Geest S. Prevalence, consequences, and determinants of nonadherence in adult renal transplant patients: a literature review. Transpl Int. 2005 Oct;18(10):1121-33. doi: 10.1111/j.1432-2277.2005.00176.x. PMID: 16162098.
  12. De Geest S, Abraham I, Moons P, Vandeputte M, Van Cleemput J, Evers G, Daenen W, Vanhaecke J. Late acute rejection and subclinical noncompliance with cyclosporine therapy in heart transplant recipients. J Heart Lung Transplant. 1998 Sep;17(9):854-63. PMID: 9773856.
  13. Bakr MA, Nagib AM, Donia AF, Denewar AA, Abu-Elmagd MM, Abbas MH, Abdel-Rahman AM, Mashaly ME, Elsaftawy MM, Ghoneim MA. Comparative analysis for optimizing the modified release tacrolimus (Advagraf) after kidney transplantation: A prospective randomized trial. Saudi J Kidney Dis Transpl. 2018 Nov-Dec;29(6):1267-1273. doi: 10.4103/1319-2442.248303. PMID: 30588956.
  14. Fanous H, Zheng R, Campbell C, Huang M, Nash MM, Rapi L, Zaltzman JS, Prasad GV. A comparison of the extended-release and standard-release formulations of tacrolimus in de novo kidney transplant recipients: a 12-month outcome study. Clin Kidney J. 2013 Feb;6(1):45-49. doi: 10.1093/ckj/sfs169. Epub 2012 Jan 1. PMID: 23372940; PMCID: PMC3560378.

Figures:

Figure 1

Figure 1

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Help ?