Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial

1. Ensor CR, Trofe-Clark J, Gabardi S, McDevitt-Potter LM, Shullo MA. Generic maintenance immunosuppression in solid organ transplant recipients. Pharmacotherapy. 2011;31(11):1111–29. Epub 2011/10/27. doi: 10.1592/phco.31.11.1111 22026398.

2. O’Neil J. How increased competition from generic drugs has affected prices and returns in the pharmaceutical industry. Congressional Budget Office 1988 [cited 2012 May 29]. Available from: http://www.fda.gov/ohrms/DOCKETS/dailys/04/June04/061404/03p-0029-bkg0001-Ref-15-vol3.pdf

3. Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12(2):388–99. Epub 2011/11/16. doi: 10.1111/j.1600-6143.2011.03840.x 22081892.

4. Davit BM, Nwakama PE, Buehler GJ, Conner DP, Haidar SH, Patel DT, et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann Pharmacother. 2009;43(10):1583–97. Epub 2009/09/25. doi: 10.1345/aph.1M141 19776300.

5. Christians U, Klawitter J, Clavijo CF. Bioequivalence testing of immunosuppressants: concepts and misconceptions. Kidney Int Suppl. 2010;(115):S1–7. Epub 2010/02/13. doi: 10.1038/ki.2009.504 20150904.

6. Hauck WW, Anderson S. Measuring switchability and prescribability: when is average bioequivalence sufficient? J Pharmacokinet Biopharm. 1994;22(6):551–64. Epub 1994/12/01. 7473081.

7. Pollard S, Nashan B, Johnston A, Hoyer P, Belitsky P, Keown P, et al. A pharmacokinetic and clinical review of the potential clinical impact of using different formulations of cyclosporin A. Berlin, Germany, November 19, 2001. Clin Ther. 2003;25(6):1654–69. Epub 2003/07/16. 12860490.

8. Alloway RR, Isaacs R, Lake K, Hoyer P, First R, Helderman H, et al. Report of the American Society of Transplantation conference on immunosuppressive drugs and the use of generic immunosuppressants. Am J Transplant. 2003;3(10):1211–5. Epub 2003/09/27. 14510694.

9. Harrison JJ, Schiff JR, Coursol CJ, Daley CJ, Dipchand AI, Heywood NM, et al. Generic immunosuppression in solid organ transplantation: a Canadian perspective. Transplantation. 2012;93(7):657–65. Epub 2012/01/24. doi: 10.1097/TP.0b013e3182445e9d 22267158.

10. van Gelder T. European Society for Organ Transplantation Advisory Committee recommendations on generic substitution of immunosuppressive drugs. Transpl Int. 2011;24(12):1135–41. Epub 2011/10/29. 10.1111/j.1432-2277.2011.01378.x. 22032583. doi: 10.1111/j.1432-2277.2011.01378.x 22032583

11. Uber PA, Ross HJ, Zuckermann AO, Sweet SC, Corris PA, McNeil K, et al. Generic drug immunosuppression in thoracic transplantation: an ISHLT educational advisory. J Heart Lung Transplant. 2009;28(7):655–60. Epub 2009/06/30. 10.1016/j.healun.2009.05.001. 19560691. doi: 10.1016/j.healun.2009.05.001 19560691

12. Klintmalm GB. Immunosuppression, generic drugs and the FDA. Am J Transplant. 2011;11(9):1765–6. Epub 2011/07/29. doi: 10.1111/j.1600-6143.2011.03616.x 21794082.

13. Molnar AO, Fergusson D, Tsampalieros AK, Bennett A, Fergusson N, Ramsay T, et al. Generic immunosuppression in solid organ transplantation: systematic review and meta-analysis. BMJ. 2015;350:h3163. Epub 2015/06/24. doi: 10.1136/bmj.h3163 26101226; PubMed Central PMCID: PMCPMC4476317.

14. European Medicines Agency. European Medicines Agency. Guideline on the Investigation of Bioequivalence London, UK2010 [cited 2016 October 26]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf

15. Health Canada. Guidance Document—Comparative Bioavailability Standards: Formulations Used for Systemic Effects Ottawa, Ontario: Health Canada; 2012 [cited 2016 October 26]. Available from: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/prodpharma/applic-demande/guide-ld/bio/gd_standards_ld_normes-eng.pdf

16. Food and Drug Administration. Draft Guidance on Tacrolimus 2014 [cited 2015 December 2]. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM406344.pdf

17. Yu LX, Jiang W, Zhang X, Lionberger R, Makhlouf F, Schuirmann DJ, et al. Novel bioequivalence approach for narrow therapeutic index drugs. Clin Pharmacol Ther. 2015;97(3):286–91. Epub 2015/02/12. doi: 10.1002/cpt.28 25669762.

18. Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015;98(1):19–24. Epub 2015/03/25. doi: 10.1002/cpt.113 25801146; PubMed Central PMCID: PMCPMC4481158.

19. Picard N, Bergan S, Marquet P, van Gelder T, Wallemacq P, Hesselink DA, et al. Pharmacogenetic Biomarkers Predictive of the Pharmacokinetics and Pharmacodynamics of Immunosuppressive Drugs. Ther Drug Monit. 2016;38 Suppl 1:S57–69. Epub 2015/10/16. doi: 10.1097/ftd.0000000000000255 26469711.

20. Kuypers DR, de Jonge H, Naesens M, Lerut E, Verbeke K, Vanrenterghem Y. CYP3A5 and CYP3A4 but not MDR1 single-nucleotide polymorphisms determine long-term tacrolimus disposition and drug-related nephrotoxicity in renal recipients. Clin Pharmacol Ther. 2007;82(6):711–25. Epub 2007/05/15. doi: 10.1038/sj.clpt.6100216 17495880.

21. Pallet N, Jannot AS, El Bahri M, Etienne I, Buchler M, de Ligny BH, et al. Kidney transplant recipients carrying the CYP3A4*22 allelic variant have reduced tacrolimus clearance and often reach supratherapeutic tacrolimus concentrations. Am J Transplant. 2015;15(3):800–5. Epub 2015/01/16. doi: 10.1111/ajt.13059 25588704.

22. Elens L, Hesselink DA, Bouamar R, Budde K, de Fijter JW, De Meyer M, et al. Impact of POR*28 on the pharmacokinetics of tacrolimus and cyclosporine A in renal transplant patients. Ther Drug Monit. 2014;36(1):71–9. Epub 2013/09/26. doi: 10.1097/FTD.0b013e31829da6dd 24061445.

23. Stefanovic NZ, Cvetkovic TP, Jevtovic-Stoimenov TM, Ignjatovic AM, Paunovic GJ, Velickovic RM. Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function. Exp Ther Med. 2015;10(3):1149–56. Epub 2015/12/02. doi: 10.3892/etm.2015.2598 26622455; PubMed Central PMCID: PMCPMC4533232.

24. Christians U, Jacobsen W, Benet LZ, Lampen A. Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clin Pharmacokinet. 2002;41(11):813–51. Epub 2002/08/23. doi: 10.2165/00003088-200241110-00003 12190331.

25. Food and Drug Administration. Orange Book. Approved Drug Products with Therapeutic Equivalence Evaluations 2015 [cited 2015 December 1]. Available from: http://www.accessdata.fda.gov/scripts/cder/ob/docs/queryai.cfm

26. Sandoz Tacrolimus Abbreviated New Drug Application Number A065461 [cited 2015 December 1]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=065461

27. Dr Reddy Tacrolimus Abbreviated New Drug Application Number A090509 [cited 2015 December 1]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=090509

28. Mylan Tacrolimus Abbreviated New Drug Application Number A090596 [cited 2015 December 1]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=090596

29. Accord Tacrolimus Abbreviated New Drug Application Number A091195 [cited 2015 December 1]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=091195

30. Panacea Tacrolimus Abbreviated New Drug Application Number A09082 [cited 2015 December 1]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=090802

31. Convention United SP. Tacrolimus Revision Bulletin, April 1, 2013 Rockville, MD2013 [cited 2015 December 1]. Available from: http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/revisions/tacrolimus_capsulesm.pdf

32. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. Journal of biomedical informatics. 2009;42(2):377–81. Epub 2008/10/22. doi: 10.1016/j.jbi.2008.08.010 18929686; PubMed Central PMCID: PMCPMC2700030.

33. Diletti E, Hauschke D, Steinijans VW. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharmacol Ther Toxicol. 1992;30 Suppl 1:S51–8. Epub 1992/01/01. 1601532.

34. Administration FAD. Food And Drug Administration. Guidance for Industry—Statistical Approaches to Establishing Bioequivalence Rockville, MD2001 [cited 2012 June 7]. Available from: https://www.fda.gov/downloads/drugs/guidances/ucm070244.pdf

35. Montgomery DC. Design and Analysis of Experiments. 1st ed. Wiley. 2013.

36. National Cancer Instiute. Common Toxicty Criteria for Adverse Events, v 4.0 2010 [cited 2015 December 1]. Available from: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcae_4_with_lay_terms.pdf

37. Agresti A. Categorical Data Analysis (PDF). Hooken, New Jersey: John Wiley & Sons, Inc. 2002. ISBN 0-471-36093-7

38. Daniel WW. Kruskal–Wallis one-way analysis of variance by ranks. Applied Nonparametric Statistics. 2nd ed. Boston: PWS-Kent. pp. 226–234. 1990. ISBN 0-534-91976-6

39. Sauter R, Steinijans VW, Diletti E, Bohm A, Schulz HU. Presentation of results from bioequivalence studies. Int J Clin Pharmacol Ther Toxicol. 1992;30(7):233–56. Epub 1992/07/01. 1506127.

40. Duong SQ, Lal AK, Joshi R, Feingold B, Venkataramanan R. Transition from brand to generic tacrolimus is associated with a decrease in trough blood concentration in pediatric heart transplant recipients. Pediatr Transplant. 2015;19(8):911–7. Epub 2015/10/27. doi: 10.1111/petr.12608 26497983.

41. Robertsen I, Asberg A, Ingero AO, Vethe NT, Bremer S, Bergan S, et al. Use of generic tacrolimus in elderly renal transplant recipients: precaution is needed. Transplantation. 2015;99(3):528–32. Epub 2014/08/26. doi: 10.1097/TP.0000000000000384 25148382.

42. Min SI, Ha J, Kim YS, Ahn SH, Park T, Park DD, et al. Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in de novo kidney transplant patients. Nephrol Dial Transplant. 2013;28(12):3110–9. Epub 2013/10/03. doi: 10.1093/ndt/gft300 24084327.

43. Spence MM, Nguyen LM, Hui RL, Chan J. Evaluation of clinical and safety outcomes associated with conversion from brand-name to generic tacrolimus in transplant recipients enrolled in an integrated health care system. Pharmacotherapy. 2012;32(11):981–7. Epub 2012/10/18. doi: 10.1002/phar.1130 23074134.

44. Momper JD, Ridenour TA, Schonder KS, Shapiro R, Humar A, Venkataramanan R. The impact of conversion from prograf to generic tacrolimus in liver and kidney transplant recipients with stable graft function. Am J Transplant. 2011;11(9):1861–7. Epub 2011/07/01. doi: 10.1111/j.1600-6143.2011.03615.x 21714845.

45. McDevitt-Potter LM, Sadaka B, Tichy EM, Rogers CC, Gabardi S. A multicenter experience with generic tacrolimus conversion. Transplantation. 2011;92(6):653–7. Epub 2011/07/27. doi: 10.1097/TP.0b013e31822a79ad 21788920.

46. Alloway RR, Sadaka B, Trofe-Clark J, Wiland A, Bloom RD. A randomized pharmacokinetic study of generic tacrolimus versus reference tacrolimus in kidney transplant recipients. Am J Transplant. 2012;12(10):2825–31. Epub 2012/07/05. doi: 10.1111/j.1600-6143.2012.04174.x 22759200; PubMed Central PMCID: PMCPMC3472020.

47. Bloom RD, Trofe-Clark J, Wiland A, Alloway RR. A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs. the reference formulation in subpopulations of kidney transplant patients. Clin Transplant. 2013;27(6):E685–93. Epub 2013/10/15. doi: 10.1111/ctr.12256 24118450.

48. Macphee IA, Fredericks S, Tai T, Syrris P, Carter ND, Johnston A, et al. Tacrolimus pharmacogenetics: polymorphisms associated with expression of cytochrome p4503A5 and P-glycoprotein correlate with dose requirement. Transplantation. 2002;74(11):1486–9. Epub 2002/12/20. doi: 10.1097/01.TP.0000045761.71385.9F 12490779.