Skip to main content
SpringerLink
Log in

Tacrolimus (FK506): Safety and Applications in Reconstructive Surgery

  • Review Articles of Topics
  • Published:
HAND

Abstract

Tacrolimus (FK506) is a macrolide immunosuppressive drug that is approved for the prevention of allograft rejection. It is a standard component of immunosuppressive regimens currently in use for organ and reconstructive tissue transplants. The experimental literature has demonstrated potential efficacy in the management of other diseases for which transplantation does not play a role. The ability of tacrolimus to modulate the immune system and inhibit T cell activation provides a potential benefit for the treatment of disorders in which autoimmune phenomena are central to their pathogenesis such as rheumatoid arthritis and inflammatory bowel disease. Tacrolimus also has well-established neuroprotective and neuroregenerative properties through both similar and different mechanisms that have been extensively demonstrated in both small and large animal models. However, as a potent immunosuppressive agent, it can cause serious adverse effects, some of which are irreversible and potentially life threatening. This article reviews its safety under different therapeutic requirements and applications in both allogeneic and autogenous tissue reconstruction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Reference

  1. Prescribing information for Prograf; Physician's Desk Reference. Montvale, NJ, Medical Economics Co. pp 1393–1397.

  2. Akimoto K, Kusunoki Y, Nishio S, Takagi K, Kawai S. Safety profile of tacrolimus in patients with rheumatoid arthritis. Clin Rheumatol. 2008;27:1393–7. doi:10.1007/s10067-008-0931-z.

    Article  PubMed  Google Scholar 

  3. Archibald SJ, Shefner J, Krarup C, Madison RD. Monkey median nerve repaired by nerve graft or collagen nerve guide tube. J Neurosci. 1995;15:4109–23.

    CAS  PubMed  Google Scholar 

  4. Archibald SJ, Wang MS, Gold BG. FK506 accelerates axonal regeneration through an artificial nerve guide in the rat sciatic nerve transection model. J Peripher Nerv Syst. 1999;4:202.

    Google Scholar 

  5. Avramut M, Achim CL. Immunophilins in nervous system degeneration and regeneration. Curr Top Med Chem. 2003;3:1376–82. doi:10.2174/1568026033451871.

    Article  CAS  PubMed  Google Scholar 

  6. Baumgart DC, Macdonald JK, Feagan B (2008) Tacrolimus (FK506) for induction of remission in refractory ulcerative colitis. Cochrane Database Syst Rev CD007216.

  7. Baumgart DC, Pintoffl JP, Sturm A, Wiedenmann B, Dignass AU. Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease—a long-term follow-up. Am J Gastroenterol. 2006;101:1048–56. doi:10.1111/j.1572-0241.2006.00524.x.

    Article  CAS  PubMed  Google Scholar 

  8. Bavetta S, Hamlyn PJ, Burnstock G, Lieberman AR, Anderson PN. The effects of FK506 on dorsal column axons following spinal cord injury in adult rats: neuroprotection and local regeneration. Exp Neurol. 1999;158:382–93. doi:10.1006/exnr.1999.7119.

    Article  CAS  PubMed  Google Scholar 

  9. Becker DB, Jensen JN, Myckatyn TM, Doolabh VB, Hunter DA, Mackinnon SE. Effects of FKBP-12 ligands following tibial nerve injury in rats. J Reconstr Microsurg. 2000;16:613–20. doi:10.1055/s-2000-9379.

    Article  CAS  PubMed  Google Scholar 

  10. Benson A, Barrett T, Sparberg M, Buchman AL. Efficacy and safety of tacrolimus in refractory ulcerative colitis and Crohn's disease: a single-center experience. Inflamm Bowel Dis. 2008;14:7–12. doi:10.1002/ibd.20263.

    Article  PubMed  Google Scholar 

  11. Birge RB, Wadsworth S, Akakura R, Abeysinghe H, Kanojia R, MacIelag M, et al. A role for Schwann cells in the neuroregenerative effects of a non-immunosuppressive fk506 derivative, jnj460. Neuroscience. 2004;124:351–66. doi:10.1016/j.neuroscience.2003.10.013.

    Article  CAS  PubMed  Google Scholar 

  12. Brenner MJ, Tung TH, Jensen JN, Mackinnon SE (2002) The spectrum of complications of immunosuppression: is the time right for hand transplantation? J Bone Joint Surg Am 84-A:1861–70.

    Google Scholar 

  13. Bronster DJ, Emre S, Mor E, Sheiner P, Miller CM, Schwartz ME (1994) Neurologic complications of orthotopic liver transplantation. Mt Sinai J Med 61:63–9. Review. 66 refs.

    Google Scholar 

  14. Chen GF, Gu LQ, Pei GX (2002) Peripheral nerve regeneration under immunosuppression. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 16:139–41.

  15. Chunasuwankul R, Ayrout C, Dereli Z, Gal A, Lanzetta M, Owen E. Low dose discontinued FK506 treatment enhances peripheral nerve regeneration. Int Surg. 2002;87:274–8.

    PubMed  Google Scholar 

  16. Chung S, Park CW, Song J, Kim JA, Shin SJ, Chang YS. Simultaneous and sustained remission of intractable myasthenia gravis and focal segmental glomerulosclerosis with tacrolimus treatment. Clin Nephrol. 2008;70:59–61.

    CAS  PubMed  Google Scholar 

  17. Costa A, Alessiani M, De Ponti F, Spada M, Merli M, Zanola S, et al. Stimulatory effect of FK506 and erythromycin on pig intestinal motility. Transplant Proc. 1996;28:2571–2.

    CAS  PubMed  Google Scholar 

  18. Costantini LC, Chaturvedi P, Armistead DM, McCaffrey PG, Deacon TW, Isacson O. A novel immunophilin ligand: distinct branching effects on dopaminergic neurons in culture and neurotrophic actions after oral administration in an animal model of Parkinson's disease. Neurobiol Dis. 1998;5:97–106. doi:10.1006/nbdi.1998.0185.

    Article  CAS  PubMed  Google Scholar 

  19. Cronin DC, Faust TW, Brady L, Conjeevaram H, Jain S, Gupta P, Millis JM (2000) Modern immunosuppression. Clin Liver Dis 4:619–55. Review. 220 refs. doi:10.1016/S1089-3261(05)70130-6

  20. Curran MP, Perry CM. Tacrolimus: in patients with rheumatoid arthritis. Drugs. 2005;65:993–1001. doi:10.2165/00003495-200565070-00005.

    Article  CAS  PubMed  Google Scholar 

  21. Doolabh VB, Mackinnon SE. FK506 accelerates functional recovery following nerve grafting in a rat model. Plast Reconstr Surg. 1999;103:1928–36. doi:10.1097/00006534-199906000-00018.

    Article  CAS  PubMed  Google Scholar 

  22. Dubernard JM, Owen E, Herzberg G, Lanzetta M, Martin X, Kapila H, et al. Human hand allograft: report on first 6 months. Lancet. 1999;353:1315–20. doi:10.1016/S0140-6736(99)02062-0.

    Article  CAS  PubMed  Google Scholar 

  23. Dubernard JM, Owen E, Herzberg G, Martin X, Guigal V, Dawahra M, et al. The first transplantation of a hand in humans. Early results. Chirurgie. 1999;124:358–65. doi:10.1016/S0001-4001(00)80007-0.

    Article  CAS  PubMed  Google Scholar 

  24. Dubernard JM, Petruzzo P, Lanzetta M, Parmentier H, Martin X, Dawahra M, et al. Functional results of the first human double-hand transplantation. Ann Surg. 2003;238:128–36. doi:10.1097/00000658-200307000-00017.

    Article  PubMed  Google Scholar 

  25. Emborg ME, Shin P, Roitberg B, Sramek JG, Chu Y, Stebbins GT, et al. Systemic administration of the immunophilin ligand GPI 1046 in MPTP-treated monkeys. Exp Neurol. 2001;168:171–82. doi:10.1006/exnr.2000.7592.

    Article  CAS  PubMed  Google Scholar 

  26. Fansa H, Keilhoff G, Altmann S, Plogmeier K, Wolf G, Schneider W (1999) The effect of the immunosuppressant FK 506 on peripheral nerve regeneration following nerve grafting. J Hand Surg [Br] 24:38–42. doi:10.1016/S0266-7681(99)90021-9

    Google Scholar 

  27. Fansa H, Keilhoff G, Horn T, Altmann S, Wolf G, Schneider W. Stimulation of Schwann cell growth and axon regeneration of peripheral nerves by the immunosuppressive drug FK 506. Handchir Mikrochir Plast Chir. 1999;31:323–9. doi:10.1055/s-1999-13544.

    Article  CAS  PubMed  Google Scholar 

  28. Furst DE, Saag K, Fleischmann MR, Sherrer Y, Block JA, Schnitzer T, et al. Efficacy of tacrolimus in rheumatoid arthritis patients who have been treated unsuccessfully with methotrexate: a six-month, double-blind, randomized, dose-ranging study. Arthritis Rheum. 2002;46:2020–8. doi:10.1002/art.10427.

    Article  CAS  PubMed  Google Scholar 

  29. Gold BG. FK506 and the role of immunophilins in nerve regeneration. Mol Neurobiol. 1997;15:285–306. doi:10.1007/BF02740664.

    Article  CAS  PubMed  Google Scholar 

  30. Gold BG. Neuroimmunophilin ligands: evaluation of their therapeutic potential for the treatment of neurological disorders. Expert Opin Investig Drugs. 2000;9:2331–42. doi:10.1517/13543784.9.10.2331.

    Article  CAS  PubMed  Google Scholar 

  31. Gold BG, Densmore V, Shou W, Matzuk MM, Gordon HS. Immunophilin FK506-binding protein 52 (not FK506-binding protein 12) mediates the neurotrophic action of FK506. J Pharmacol Exp Ther. 1999;289:1202–10.

    CAS  PubMed  Google Scholar 

  32. Gold BG, Gordon HS, Wang MS. Efficacy of delayed or discontinuous FK506 administrations on nerve regeneration in the rat sciatic nerve crush model: lack of evidence for a conditioning lesion-like effect. Neurosci Lett. 1999;267:33–6. doi:10.1016/S0304-3940(99)00333-X.

    Article  CAS  PubMed  Google Scholar 

  33. Gold BG, Katoh K, Storm-Dickerson T. The immunosuppressant FK506 increases the rate of axonal regeneration in rat sciatic nerve. J Neurosci. 1995;15:7509–16.

    CAS  PubMed  Google Scholar 

  34. Gold BG, Storm-Dickerson T, Austin DR. The immunosuppressant FK506 increases functional recovery and nerve regeneration following peripheral nerve injury. Restor Neurol Neurosci. 1994;6:287–96.

    CAS  Google Scholar 

  35. Gold R, Schneider-Gold C. Current and future standards in treatment of myasthenia gravis. Neurotherapeutics. 2008;5:535–41. doi:10.1016/j.nurt.2008.08.011.

    Article  CAS  PubMed  Google Scholar 

  36. Guimberteau JC, Baudet J, Panconi B, Boileau R, Potaux L. Human allotransplant of a digital flexion system vascularized on the ulnar pedicle: a preliminary report and 1-year follow-up of two cases. Plast Reconstr Surg. 1992;89:1135–47. doi:10.1097/00006534-199206000-00023.

    Article  CAS  PubMed  Google Scholar 

  37. Guo X, Dawson VL, Dawson TM. Neuroimmunophilin ligands exert neuroregeneration and neuroprotection in midbrain dopaminergic neurons. Eur J Neurosci. 2001;13:1683–93. doi:10.1046/j.0953-816x.2001.01542.x.

    Article  CAS  PubMed  Google Scholar 

  38. Guo X, Dillman JF III, Dawson VL, Dawson TM. Neuroimmunophilins: novel neuroprotective and neuroregenerative targets. Ann Neurol. 2001;50:6–16. doi:10.1002/ana.1030.

    Article  CAS  PubMed  Google Scholar 

  39. Hart IK, Sharshar T, Sathasivam S. Immunosuppressant drugs for myasthenia gravis. J Neurol Neurosurg Psychiatry. 2009;80:5–6. doi:10.1136/jnnp. 2008.144980.

    Article  CAS  PubMed  Google Scholar 

  40. Hassan J, van der Net JJ, Royen-Kerkhof A. Treatment of refractory juvenile dermatomyositis with tacrolimus. Clin Rheumatol. 2008;27:1469–71. doi:10.1007/s10067-008-0973-2.

    Article  PubMed  Google Scholar 

  41. Hoekstra HJ, Hawkins K, de Boer WJ, Rottier K, van der BW. Gastrointestinal complications in lung transplant survivors that require surgical intervention. Br J Surg. 2001;88:433–8. doi:10.1046/j.1365-2168.2001.01693.x.

    Article  CAS  PubMed  Google Scholar 

  42. Hofmann GO, Kirschner MH, Brauns L, Wagner FD, Land W, Buhren V. Vascularized knee joint transplantation in man: a report on the first cases. Transpl Int. 1998;11(Suppl 1):S487–90.

    PubMed  Google Scholar 

  43. Hofmann GO, Kirschner MH, Wagner FD, Brauns L, Gonschorek O, Buhren V. Allogeneic vascularized transplantation of human femoral diaphyses and total knee joints—first clinical experiences. Transplant Proc. 1998;30:2754–61. doi:10.1016/S0041-1345(98)00803-3.

    Article  CAS  PubMed  Google Scholar 

  44. Ishigaki K, Shishikura K, Murakami T, Suzuki H, Hirayama Y, Osawa M Benefits of FK 506 for refractory eye symptoms in a young child with ocular myasthenia gravis. Brain Dev. 2008. doi:10.1016/j.braindev.2008.08.016.

  45. Itoh Z, Nakaya M, Suzuki T, Arai H, Wakabayashi K. Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog. Am J Physiol. 1984;247:G688–94.

    CAS  PubMed  Google Scholar 

  46. Itoh Z, Suzuki T, Nakaya M, Inoue M, Arai H, Wakabayashi K. Structure–activity relation among macrolide antibiotics in initiation of interdigestive migrating contractions in the canine gastrointestinal tract. Am J Physiol. 1985;248:G320–5.

    CAS  PubMed  Google Scholar 

  47. Itoh Z, Suzuki T, Nakaya M, Inoue M, Mitsuhashi S. Gastrointestinal motor-stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut. Antimicrob Agents Chemother. 1984;26:863–9.

    CAS  PubMed  Google Scholar 

  48. Jap A, Chee SP. Immunosuppressive therapy for ocular diseases. Curr Opin Ophthalmol. 2008;19:535–40. doi:10.1097/ICU.0b013e3283126d20.

    Article  PubMed  Google Scholar 

  49. Jones JW, Gruber SA, Barker JH, Breidenbach WC. Successful hand transplantation: one-year follow-up. N Engl J Med. 2000;343:468–73. doi:10.1056/NEJM200008173430704.

    Article  CAS  PubMed  Google Scholar 

  50. Jost SC, Doolabh VB, Mackinnon SE, Lee M, Hunter D. Acceleration of peripheral nerve regeneration following FK506 administration. Restor Neurol Neurosci. 2000;17:39–44.

    CAS  PubMed  Google Scholar 

  51. Kawai S, Hashimoto H, Kondo H, Murayama T, Kiuchi T, Abe T. Comparison of tacrolimus and mizoribine in a randomized, double-blind controlled study in patients with rheumatoid arthritis. J Rheumatol. 2006;33:2153–61.

    CAS  PubMed  Google Scholar 

  52. Kondo H, Abe T, Hashimoto H, Uchida S, Irimajiri S, Hara M, et al. Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study. J Rheumatol. 2004;31:243–51.

    CAS  PubMed  Google Scholar 

  53. Kwok BW, Hunt SA (2000) Neoplasia after heart transplantation. Cardiol Rev 8:256–9. Review. 24 refs. doi:10.1097/00045415-200008050-00004

    Google Scholar 

  54. Lee M, Doolabh VB, Mackinnon SE, Jost S. FK506 promotes functional recovery in crushed rat sciatic nerve. Muscle Nerve. 2000;23:633–40. doi:10.1002/(SICI)1097–4598(200004)23:4<633::AID-MUS24>3.0.CO;2-Q.

    Article  CAS  PubMed  Google Scholar 

  55. Mackinnon SE, Doolabh VB, Novak CB, Trulock EP. Clinical outcome following nerve allograft transplantation. Plast Reconstr Surg. 2001;107:1419–29. doi:10.1097/00006534-200105000-00016.

    Article  CAS  PubMed  Google Scholar 

  56. Mackinnon SE, Hudson AR. Clinical application of peripheral nerve transplantation. Plast Reconstr Surg. 1992;90:695–9. doi:10.1097/00006534-199210000-00024.

    Article  CAS  PubMed  Google Scholar 

  57. Madsen JR, MacDonald P, Irwin N, Goldberg DE, Yao GL, Meiri KF, et al. Tacrolimus (FK506) increases neuronal expression of GAP-43 and improves functional recovery after spinal cord injury in rats. Exp Neurol. 1998;154:673–83. doi:10.1006/exnr.1998.6974.

    Article  CAS  PubMed  Google Scholar 

  58. Maes BD, Vanwalleghem J, Kuypers D, Ghoos Y, Rutgeerts PJ, Vanrenterghem YF. Differences in gastric motor activity in renal transplant recipients treated with FK-506 versus cyclosporine. Transplantation. 1999;68:1482–5. doi:10.1097/00007890-199911270-00009.

    Article  CAS  PubMed  Google Scholar 

  59. Margreiter R. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet. 2002;359:741–6. doi:10.1016/S0140-6736(02)07875-3.

    Article  CAS  PubMed  Google Scholar 

  60. Margreiter R, Brandacher G, Ninkovic M, Steurer W, Kreczy A, Schneeberger S. A double-hand transplant can be worth the effort!. Transplantation. 2002;74:85–90. doi:10.1097/00007890-200207150-00015.

    Article  PubMed  Google Scholar 

  61. Martin D, Pinsolle V, Merville P, Moreau K, Pelissier P, Baudet J. First case in the world of autoreplantation of a limb associated with oral administration of an immunosupressant agent (FK 506—Tacrolimus). Ann Chir Plast Esthet. 2005;50:257–63. doi:10.1016/j.anplas.2005.02.001.

    Article  CAS  PubMed  Google Scholar 

  62. Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, et al. Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation. 1997;64:436–43. doi:10.1097/00007890-199708150-00012.

    Article  CAS  PubMed  Google Scholar 

  63. Mor E, Schwersenz A, Sheiner PA, Emre S, Schwartz ME, Miller CM. Reversal of gastrointestinal toxicity associated with long-term FK506 immunosuppression by conversion to cyclosporine in liver transplant recipients. Transplantation. 1994;57:1130–2. doi:10.1097/00007890-199404150-00025.

    Article  CAS  PubMed  Google Scholar 

  64. Morita Y, Sasae Y, Sakuta T, Satoh M, Sasaki T, Kashihara N. Efficacy of low-dose tacrolimus added to methotrexate in patients with rheumatoid arthritis in Japan: a retrospective study. Mod Rheumatol. 2008;18:379–84. doi:10.1007/s10165-008-0071-y.

    Article  CAS  PubMed  Google Scholar 

  65. Myckatyn TM, Ellis RA, Grand AG, Sen SK, Lowe JB III, Hunter DA, et al. The effects of rapamycin in murine peripheral nerve isografts and allografts. Plast Reconstr Surg. 2002;109:2405–17. doi:10.1097/00006534-200206000-00035.

    Article  PubMed  Google Scholar 

  66. Nagaishi A, Yukitake M, Kuroda Y. Long-term treatment of steroid-dependent myasthenia gravis patients with low-dose tacrolimus. Intern Med. 2008;47:731–6. doi:10.2169/internalmedicine.47.0513.

    Article  PubMed  Google Scholar 

  67. Naniwa T, Watanabe M, Banno S, Maeda T Adding low dose tacrolimus in rheumatoid arthritis patients with an inadequate response to tumor necrosis factor inhibitor therapies. Rheumatol. Int. 2009 (in press).

  68. Navarro X, Udina E, Ceballos D, Gold BG. Effects of FK506 on nerve regeneration and reinnervation after graft or tube repair of long nerve gaps. Muscle Nerve. 2001;24:905–15. doi:10.1002/mus.1088.

    Article  CAS  PubMed  Google Scholar 

  69. Ng SC, Arebi N, Kamm MA. Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel disease. Inflamm Bowel Dis. 2007;13:129–34. doi:10.1002/ibd.20052.

    Article  PubMed  Google Scholar 

  70. Ogata H, Matsui T, Nakamura M, Iida M, Takazoe M, Suzuki Y, et al. A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut. 2006;55:1255–62. doi:10.1136/gut.2005.081794.

    Article  CAS  PubMed  Google Scholar 

  71. Okan G, Yaylaci S, Peker O, Kaymakoglu S, Saruc M. Vanishing bile duct and Stevens–Johnson syndrome associated with ciprofloxacin treated with tacrolimus. World J Gastroenterol. 2008;14:4697–700. doi:10.3748/wjg.14.4697.

    Article  PubMed  Google Scholar 

  72. Otley CC, Pittelkow MR (2000) Skin cancer in liver transplant recipients. Liver Transpl 6:253–62. Review. 53 refs.

    Google Scholar 

  73. Pan YA, Misgeld T, Lichtman JW, Sanes JR. Effects of neurotoxic and neuroprotective agents on peripheral nerve regeneration assayed by time-lapse imaging in vivo. J Neurosci. 2003;23:11479–88.

    CAS  PubMed  Google Scholar 

  74. Pei G, Gu L, Yu L. A preliminary report of two cases of human hand allograft. Zhonghua Yi Xue Za Zhi. 2000;80:417–21.

    CAS  PubMed  Google Scholar 

  75. Penn I (2000) Post-transplant malignancy: the role of immunosuppression. Drug Saf 23:101–13. Review. 71 refs. doi:10.2165/00002018-200023020-00002

    Google Scholar 

  76. Porter GA, Bennett WM, Sheps SG. Cyclosporine-associated hypertension. Arch Intern Med. 1990;150:280–3. doi:10.1001/archinte.150.2.280.

    Article  CAS  PubMed  Google Scholar 

  77. Preiksaitis JK, Keay S (2001) Diagnosis and management of posttransplant lymphoproliferative disorder in solid-organ transplant recipients. Clin Infect Dis 33(Suppl 1):S38–46. Review. 104 refs. doi:10.1086/320903

    Google Scholar 

  78. Revill WP, Voda J, Reeves CR, Chung L, Schirmer A, Ashley G, et al. Genetically engineered analogs of ascomycin for nerve regeneration. J Pharmacol Exp Ther. 2002;302:1278–85. doi:10.1124/jpet.102.034264.

    Article  CAS  PubMed  Google Scholar 

  79. Sathasivam S. Steroids and immunosuppressant drugs in myasthenia gravis. Nat Clin Pract Neurol. 2008;4:317–27. doi:10.1038/ncpneuro0810.

    Article  CAS  PubMed  Google Scholar 

  80. Scott LJ, McKeage K, Keam SJ, Plosker GL. Tacrolimus: a further update of its use in the management of organ transplantation. Drugs. 2003;63:1247–97. doi:10.2165/00003495-200363120-00006.

    Article  CAS  PubMed  Google Scholar 

  81. Snydman DR (2001) Epidemiology of infections after solid-organ transplantation. Clin Infect Dis 33(Suppl 1):S5–8. Review. 40 refs. doi:10.1086/320897

    Google Scholar 

  82. Sosa I, Reyes O, Kuffler DP. Immunosuppressants: neuroprotection and promoting neurological recovery following peripheral nerve and spinal cord lesions. Exp Neurol. 2005;195:7–15. doi:10.1016/j.expneurol.2005.04.016.

    Article  CAS  PubMed  Google Scholar 

  83. Strome M, Stein J, Esclamado R, Hicks D, Lorenz RR, Braun W, et al. Laryngeal transplantation and 40-month follow-up. N Engl J Med. 2001;344:1676–9. doi:10.1056/NEJM200105313442204.

    Article  CAS  PubMed  Google Scholar 

  84. Sugawara T, Itoh Y, Mizoi K. Immunosuppressants promote adult dorsal root regeneration into the spinal cord. Neuroreport. 1999;10:3949–53. doi:10.1097/00001756-199912160-00041.

    Article  CAS  PubMed  Google Scholar 

  85. Sulaiman OA, Voda J, Gold BG, Gordon T. FK506 increases peripheral nerve regeneration after chronic axotomy but not after chronic Schwann cell denervation. Exp Neurol. 2002;175:127–37. doi:10.1006/exnr.2002.7878.

    Article  CAS  PubMed  Google Scholar 

  86. Suzuki K, Kameda H, Amano K, Nagasawa H, Takei H, Sekiguchi N, et al. Single center prospective study of tacrolimus efficacy and safety in treatment of rheumatoid arthritis. Rheumatol Int. 2009;29:431–6. doi:10.1007/s00296-008-0833-z.

    Article  CAS  PubMed  Google Scholar 

  87. Szeto CC, Kwan BC, Lai FM, Tam LS, Li EK, Chow KM, et al. Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis. Rheumatology (Oxford). 2008;47:1678–81. doi:10.1093/rheumatology/ken335.

    Article  CAS  Google Scholar 

  88. Tamaki H, Nakase H, Matsuura M, Inoue S, Mikami S, Ueno S, et al. The effect of tacrolimus (FK-506) on Japanese patients with refractory Crohn's disease. J Gastroenterol. 2008;43:774–9. doi:10.1007/s00535-008-2229-y.

    Article  CAS  PubMed  Google Scholar 

  89. The US. Multicenter FK506 Liver Study Group: a comparison of tacrolimus (FK506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med. 2004;331:1110–5.

    Google Scholar 

  90. Udina E, Ceballos D, Gold BG, Navarro X. FK506 enhances reinnervation by regeneration and by collateral sprouting of peripheral nerve fibers. Exp Neurol. 2003;183:220–31. doi:10.1016/S0014-4886(03)00173-0.

    Article  CAS  PubMed  Google Scholar 

  91. Udina E, Navarro X. Immunophilins: neuroprotective agents and promoters of neural regeneration. Neurologia. 2002;17:200–13. doi:10.1159/000059370.

    CAS  PubMed  Google Scholar 

  92. Udina E, Voda J, Gold BG, Navarro X. Comparative dose-dependence study of FK506 on transected mouse sciatic nerve repaired by allograft or xenograft. J Peripher Nerv Syst. 2003;8:145–54. doi:10.1046/j.1529-8027.2003.03020.x.

    Article  PubMed  Google Scholar 

  93. Wang MS, Gold BG. FK506 increases the regeneration of spinal cord axons in a predegenerated peripheral nerve autograft. J Spinal Cord Med. 1999;22:287–96.

    CAS  PubMed  Google Scholar 

  94. Wang MS, Zeleny-Pooley M, Gold BG. Comparative dose-dependence study of FK506 and cyclosporin A on the rate of axonal regeneration in the rat sciatic nerve. J Pharmacol Exp Ther. 1997;282:1084–93.

    CAS  PubMed  Google Scholar 

  95. Woolfson RG, Neild GH (1997) Cyclosporin nephrotoxicity following cardiac transplantation. Nephrol Dial Transplant 12:2054–6. Review. 26 refs. doi:10.1093/ndt/12.10.2054

    Google Scholar 

  96. Yamamoto S, Nakase H, Mikami S, Inoue S, Yoshino T, Takeda Y, et al. Long-term effect of tacrolimus therapy in patients with refractory ulcerative colitis. Aliment Pharmacol Ther. 2008;28:589–97. doi:10.1111/j.1365-2036.2008.03764.x.

    Article  CAS  PubMed  Google Scholar 

  97. Yamani MH, Starling RC (2000) Long-term medical complications of heart transplantation: information for the primary care physician. Cleve Clin J Med 67:673–80. Review. 48 refs.

    Google Scholar 

  98. Yang RK, Lowe JB III, Sobol JB, Sen SK, Hunter DA, Mackinnon SE. Dose-dependent effects of FK506 on neuroregeneration in a rat model. Plast Reconstr Surg. 2003;112:1832–40. doi:10.1097/01.PRS.0000091167.27303.18.

    Article  PubMed  Google Scholar 

  99. Yildirim FB, Sarikcioglu L, Ozsoy U, Demir N, Demirtop A, Ucar Y. Effect of FK506 administration after obturator nerve injury: a functional and ultrastructural study. Acta Neurobiol Exp (Warsz). 2008;68:477–83.

    Google Scholar 

  100. Yocum DE, Furst DE, Bensen WG, Burch FX, Borton MA, Mengle-Gaw LJ, et al. Safety of tacrolimus in patients with rheumatoid arthritis: long-term experience. Rheumatology (Oxford). 2004;43:992–9. doi:10.1093/rheumatology/keh155.

    Article  CAS  Google Scholar 

  101. Yocum DE, Furst DE, Kaine JL, Baldassare AR, Stevenson JT, Borton MA, et al. Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: a double-blind trial. Arthritis Rheum. 2003;48:3328–37. doi:10.1002/art.11363.

    Article  CAS  PubMed  Google Scholar 

  102. Yokota K, Akiyama Y, Asanuma Y, Miyoshi F, Sato K, Mimura T. Efficacy of tacrolimus in infliximab-refractory progressive rheumatoid arthritis. Rheumatol Int. 2009;29:459–61. doi:10.1007/s00296-008-0694-5.

    Article  CAS  PubMed  Google Scholar 

  103. Yoshida S, Kotani T, Takeuchi T, Isoda K, Hata K, Watanabe K, et al. Successful treatment of early intervention with tacrolimus for a patient with lupus nephritis III + V. Nihon Rinsho Meneki Gakkai Kaishi. 2008;31:460–4. doi:10.2177/jsci.31.460.

    CAS  PubMed  Google Scholar 

  104. Zietse R, Balk AH, Dorpel MA vd, Meeter K, Bose E, Weimar W. Time course of the decline in renal function in cyclosporine-treated heart transplant recipients. Am J Nephrol. 1994;14:1–5. doi:10.1159/000168677.

    Article  CAS  PubMed  Google Scholar 

  105. Ziring DA, Wu SS, Mow WS, Martin MG, Mehra M, Ament ME. Oral tacrolimus for steroid-dependent and steroid-resistant ulcerative colitis in children. J Pediatr Gastroenterol Nutr. 2007;45:306–11.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, Saint Louis, MO, USA

    Thomas H. Tung

Authors
  1. Thomas H. Tung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas H. Tung.

About this article

Cite this article

Tung, T.H. Tacrolimus (FK506): Safety and Applications in Reconstructive Surgery. HAND 5, 1–8 (2010). https://doi.org/10.1007/s11552-009-9193-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11552-009-9193-8

Keywords

Search

Navigation