, Volume 63, Issue 12, pp 1247–1297 | Cite as


A Further Update of its Use in the Management of Organ Transplantation
  • Lesley J. ScottEmail author
  • Kate McKeage
  • Susan J. Keam
  • Greg L Plosker
Adis Drug Evaluation



Extensive clinical use has confirmed that tacrolimus (Prograf®) is a key option for immunosuppression after transplantation. In large, prospective, randomised, multicentre trials in adults and children receiving solid organ transplants, tacrolimus was at least as effective or provided better efficacy than cyclosporin microemulsion in terms of patient and graft survival, treatment failure rates and the incidence of biopsy-proven acute and corticosteroid-resistant rejection episodes. Notably, the lower incidence of rejection episodes after renal transplantation in tacrolimus recipients was reflected in improved cost effectiveness. In bone marrow transplant (BMT) recipients, the incidence of tacrolimus grade II–IV graft-versus-host disease was significantly lower with tacrolimus than cyclosporin treatment. Efficacy was maintained in renal and liver transplant recipients after total withdrawal of corticosteroid therapy from tacrolimus-based immunosuppression, with the incidence of acute rejection episodes at up to 2 years’ follow-up being similar with or without corticosteroids.

Tacrolimus provided effective rescue therapy in transplant recipients with persistent acute or chronic allograft rejection or drug-related toxicity associated with cyclosporin treatment. Typically, conversion to tacrolimus reversed rejection episodes and/or improved the tolerability profile, particularly in terms of reduced hyperlipidaemia. In lung transplant recipients with obliterative bronchiolitis, conversion to tacrolimus reduced the decline in and/or improved lung function in terms of forced expiratory volume in 1 second.

Tolerability issues may be a factor when choosing a calcineurin inhibitor. Cyclosporin tends to be associated with a higher incidence of significant hypertension, hyperlipidaemia, hirsutism, gingivitis and gum hyperplasia, whereas the incidence of some types of neurotoxicity, disturbances in glucose metabolism, diarrhoea, pruritus and alopecia may be higher with tacrolimus treatment. Renal function, as assessed by serum creatinine levels and glomerular filtration rates, was better in tacrolimus than cyclosporin recipients at up to 5 years’ follow-up.

Conclusion: Recent well designed trials have consolidated the place of tacrolimus as an important choice for primary immunosuppression in solid organ transplantation and in BMT. Notably, in adults and children receiving transplants, tacrolimus-based primary immunosuppression was at least as effective or provided better efficacy than cyclosporin microemulsion treatment in terms of patient and graft survival, treatment failure and the incidence of acute and corticosteroid-resistant rejection episodes. The reduced incidence of rejection episodes in renal transplant recipients receiving tacrolimus translated into a better cost effectiveness relative to cyclosporin microemulsion treatment. The optimal immunosuppression regimen is ultimately dependent on balancing such factors as the efficacy of the individual drugs, their tolerability, potential for drug interactions and pharmacoeconomic issues.

Overview of Pharmacodynamic Properties

Tacrolimus modulates cell-mediated and humoral immune responses associated with allograft rejection in several ways. The pivotal mechanism of action involves inhibition of the signal transduction pathway leading to T-cell activation via complex formation of the drug with the immunophilin FK506 binding protein 12, thus blocking the phosphotase activity of calcineurin and subsequent production of interleukin (IL)-2. Although cyclosporin also inhibits calcineurin through complex formation with a separate immunophilin, in vitro and in vivo studies demonstrate that tacrolimus is 10–100 times more effective than cyclosporin in its ability to exert immunosuppressive actions. Tacrolimus may also inhibit cellular activities such as nitric oxide synthetase activation and apoptosis, and may potentiate the action of corticosteroids in these processes.

Overview of Pharmacokinetic Properties

Tacrolimus treatment is associated with several other well established effects including nephrotoxic, diabetogenic, neurological and cardiovascular effects, with several cellular and immunological mechanisms potentially involved. Many of these effects appear to be mechanistically related through inhibition of calcineurin and thus, are also associated with cyclosporin treatment. Tacrolimus may be less atherogenic than cyclosporin, in terms of its lipogenic potential. Like cyclosporin, pharmacokinetic parameters of tacrolimus show high inter- and intraindividual variability and both drugs have a narrow therapeutic index, necessitating therapeutic whole-blood drug monitoring to optimise treatment. Absorption and oral bioavailability (≈25%) of tacrolimus is poor, with the rate and extent of absorption reduced in the presence of food. Tacrolimus is rapidly, albeit incompletely, absorbed in the gastrointestinal tract, with peak tacrolimus concentrations in whole blood (Cmax) attained approximately 1–2 hours after oral administration. In adult renal and liver transplant recipients receiving oral tacrolimus 0.3 mg/kg/day, respective Cmax values were 24.2 and 68.5 ng/mL, with corresponding area under the concentration-time curve values of 288 and 519 ng · h/mL.

Tacrolimus is extensively bound to erythrocytes, with blood: plasma ratios showing wide variation (mean 35). Plasma protein binding may be as high as 99%, with the majority of the drug bound to α1-acid glycoprotein and albumin. The drug is widely distributed into most tissues. In renal and liver transplant recipients receiving intravenous tacrolimus, the volume of distribution was 1.41 and 0.85 L/kg. Tacrolimus crosses the placenta, with umbilical cord plasma concentrations approximately one-third of those in maternal plasma, and is present in breast milk at similar levels to those reported in the plasma.

Tacrolimus is almost completely metabolised prior to elimination. Metabolism is via cytochrome P450 (CYP) 3A4 isoenzymes in the liver and, to a lesser extent, CYP3A4 isoenzymes and P-glycoprotein in the intestinal mucosa. Several metabolites are formed and, although at least one of these shows some immunosuppressive activity, the immunosuppressive activity of tacrolimus is chiefly due to the parent drug. The elimination half-life of the drug ranged from 12–19 hours in adult transplant recipients, with less than 1% of the dose excreted as parent drug in the urine. The main route of elimination is via the biliary tract and excretion in faeces.

Poor bioavailability is observed in a higher percentage of non-Caucasian (African-American, Hispanics) than Caucasian patients, with a study in renal transplant recipients showing that African-American recipients required higher dosages of tacrolimus on a milligram per kilogram basis. Clearance of tacrolimus appears to be higher in children than adults; therefore children require higher dosages on a milligram per kilogram basis than adults. Clearance of the drug is reduced in adults with severe hepatic impairment (mean Child Pugh >10) compared with healthy adult volunteers.

Like cyclosporin, tacrolimus is subject to a number of pharmacokinetic drug interactions of potential clinical significance, including those involving other drugs metabolised by the CYP enzyme system. The main CYP3A4 inhibitors that may potentially increase whole-blood tacrolimus concentrations are various calcium antagonists (diltiazem, nicardipine, nifedipine and verapamil), imidazole antifungal agents (clotrimazole, fluconazole, itraconazole and ketoconazole), macrolide antibacterial agents (clarithromycin and erythromycin), prokinetic agents (cisapride and metoclopramide), and other drugs (bromocriptine, cimetidine, corticosteroids, cyclosporin, danazol and protease inhibitors) and grapefruit juice. Enzyme inducers that may decrease tacrolimus concentrations include certain anticonvulsants (carbamazepine, phenobarbital and phenytoin), as well as rifabutin and rifampicin (rifampin).

Therapeutic Efficacy

Tacrolimus is an established agent for primary immunosuppression and rescue therapy in solid organ transplant and bone marrow transplant (BMT) recipients. Typically, protocols for tacrolimus-based primary immunosuppression initially included corticosteroids and, in general, azathioprine or mycophenolate mofetil, with some patients also receiving adjunctive antilymphocyte antibody therapy. Rescue therapy with tacrolimus involved conversion from cyclosporin to tacrolimus, generally without modification of concomitant drug therapy. Unless stated otherwise, all analyses were intent-to-treat and clinical trials (n > 100 patients per trial) evaluating primary immunosuppression were prospective, randomised, nonblind and multicentre in design.

Renal transplantation: At 5 years’ follow-up, tacrolimus provided better efficacy than cyclosporin microemulsion in intent-to-treat analyses, in terms of graft survival (79% vs 54%; p < 0.0001), the number of patients who switched to the other calcineurin inhibitor (5% vs 27% of cyclosporin microemulsion recipients; p < 0.001) and in terms of treatment failure (21% vs 56%; p < 0.001). At earlier timepoints (12–36 months post-transplantation), patient- and graft-survival rates were similar in both treatment groups in three recent trials. Notably, at 6 months’ follow-up, the incidence of biopsy-proven acute rejection episodes was significantly lower with tacrolimus-based treatment than with cyclosporin microemulsion therapy (19.6% vs 37.3%; p < 0.001) in the largest trial. Tacrolimus recipients also showed better renal function than cyclosporin microemulsion recipients at up to 5 years’ follow-up, as assessed by serum creatinine levels and glomerular filtration rates.

Dual therapy with tacrolimus-based immunosuppression provided equivalent efficacy to tacrolimus-based triple therapy at up to 36 months’ follow-up in adult renal transplant recipients. In two other trials, corticosteroid therapy could effectively be withdrawn from tacrolimus-based immunosuppression. Preliminary data from prospective trials (n = 104–266 evaluable patients) indicated that tacrolimus in combination with sirolimus and a corticosteroid provided effective immunosuppression therapy in renal transplant recipients. A reduced dosage of tacrolimus in combination with sirolimus and a corticosteroid was as effective as the same regimen with standard dosages of tacrolimus in one of these trials.

Tacrolimus-based rescue therapy is effective in adult patients with persistent acute or chronic rejection or drug-related toxicity during cyclosporin microemulsion treatment after renal transplant, typically improving serum lipid profiles and reversing chronic rejection.

In general, the efficacy of tacrolimus-based primary immunosuppression and rescue therapy for children and adolescents who received renal transplants was similar to that reported in adults. Notably, tacrolimus recipients showed better efficacy in terms of the incidence of biopsy-proven acute and corticosteroid-resistant rejection episodes at 6 months’ follow-up than cyclosporin microemulsion treatment when used for primary immunosuppression.

Two large nonrandomised, single-centre studies in adult renal transplant recipients indicated that tacrolimus-based immunosuppressive regimens improved disease-specific quality of life (QOL) compared with cyclosporin-based regimens.

Liver transplantation: At 12 months’ follow-up, tacrolimus-based immunosuppression provided better efficacy than cyclosporin microemulsion in terms of patient survival in a prospective, multicentre trial in 606 liver transplant recipients. There were also significantly fewer retransplantations (4% vs 10% of patients; p < 0.05) and treatment failures for immunological reasons (2% vs 4%; p < 0.05) with tacrolimus treatment than with cyclosporin microemulsion therapy, with a significantly greater proportion of tacrolimus recipients achieving the primary outcome at this timepoint (freedom from death, retransplantation or treatment failure for immunological reasons) [21% vs 32%, p = 0.001; time-to-event analysis log-rank test p = 0.002]. Furthermore, graft survival favoured tacrolimus recipients although this difference was not statistically significant (80% vs 66% in the cyclosporin microemulsion group). In a retrospective trial and two single-centre trials, tacrolimus rescue therapy was effective in adult liver transplant recipients experiencing acute cellular or chronic rejections, or drug-related toxicity during cyclosporin microemulsion treatment.

In children and adolescent liver transplant recipients receiving tacrolimus-based primary immunosuppression, patient (93.4% vs 92.2%) and graft survival (92.3% vs 85.4%) rates were similar to those in the cyclosporin microemulsion group at 12 months. However, biopsy-proven acute rejection (44.5% vs 59.8%; p < 0.05) and corticosteroid-resistant rejection (6% vs 29.6%; p < 0.001) rates were significantly lower with tacrolimus treatment. The efficacy of tacrolimus rescue therapy in children and adolescent liver transplant patients was similar to that observed in adults.

Heart transplantation: Recent trials have shown that tacrolimus-based regimens provided effective primary immunosuppression in adult heart transplant recipients, with similar patient survival rates at 22–36 months (76–97%) to those achieved with cyclosporin microemulsion-based therapy (72–95%). All analyses were on-treatment. In general, fewer recipients of tacrolimus-based immunosuppression experienced acute rejection episodes than cyclosporin recipients, although this difference was not always statistically significant. Tacrolimus-based primary immunosuppression provided statistically significant and clinically relevant improvements in health-related QOL from baseline, with improvements generally occurring earlier and to a greater extent in the tacrolimus group than in the cyclosporin group (standard formulation).

In several small studies in adult heart transplant recipients, tacrolimus-based rescue therapy was effective in the vast majority of patients at up to 3 years of follow-up, with patients showing marked improvements in systolic and diastolic blood pressure, total serum cholesterol levels and triglyceride levels. Furthermore, tacrolimus rescue therapy stabilised lung function at up to 1-year follow-up in recipients with bronchiolitis obliterans syndrome at the time of conversion from cyclosporin.

Lung transplantation: In prospective trials, tacrolimus-based primary immunosuppression was at least as effective as cyclosporin-based regimens (formulation not specified) in adult lung transplant recipients. Patient survival at 12 months was ≥73% in the tacrolimus groups versus >-72% with cyclosporin-based immunosuppression. Although in one trial, the incidence of acute rejection episodes per 100 patient-days was appreciably lower in tacrolimus than cyclosporin recipients, in the larger trial there was no between-group difference in this parameter. Also, significantly fewer tacrolimus than cyclosporin recipients required crossover to the alternative immunosuppressant because of rejection or other reasons in this latter trial (9% vs 33% of recipients; p = 0.0004). Tacrolimus-based immunosuppression also proved effective as rescue therapy in adult lung transplant recipients in small nonrandomised studies and a large retrospective study. In the latter study, there was a marked reduction in the mean number of histologically and clinically diagnosed rejection episodes after conversion. Moreover, all studies suggested that the rate of decline in pulmonary function (based on forced expiratory volume in 1 second) may have decreased or lung function may even be improved with tacrolimus rescue therapy in patients who developed bronchiolitis obliterans syndrome while receiving cyclosporin-based immunosuppression.

Simultaneous pancreas and kidney transplantation: Tacrolimus-based immunosuppression was at least as effective as cyclosporin microemulsion therapy in adult simultaneous pancreas and kidney (SPK) transplant recipients in a recent large, randomised trial. Pancreas graft survival was significantly better at 1 year in the tacrolimus group than the cyclosporin group (91.2% vs 73.9%; p < 0.001), although there was no between-group difference in patient or kidney graft survival. Tacrolimus recipients also experienced better efficacy in terms of biopsy-proven rejection episodes of grades 2 and 3, and in the duration of the initial hospital stay. In two single-centre studies, the majority of SPK recipients receiving tacrolimus-based immunosuppression were effectively withdrawn from corticosteroid treatment at some point post-transplantation.

Bone marrow transplantation: At 2–2.5 years’ follow-up, the incidence of grade II–IV acute graft-versus-host disease (GVHD) was consistently lower with tacrolimus-than cyclosporin-based immunosuppression after allogenic BMT in two trials. Kaplan-Meier estimates for the probability of survival were not significantly different between treatment groups. Furthermore, the severity of acute GVHD across all grades was markedly reduced in the tacrolimus group compared with the cyclosporin group. In general, tacrolimus rescue therapy proved effective in patients who developed acute or chronic GVHD, or drug-related toxicity during cyclosporin primary immunosuppression.


Commonly reported treatment-emergent adverse events associated with tacrolimus-based immunosuppression included nephrotoxicity, neurotoxicity, diarrhoea and other GI disturbances, increased risk of infections (viral, bacterial and fungal) and malignancies, hypertension and disturbances in glucose metabolism. All of these adverse events also occurred with cyclosporin-based immunosuppression. Furthermore, tacrolimus recipients showed better renal function than cyclosporin microemulsion recipients at up to 5 years’ follow-up, as assessed by serum creatinine levels and glomerular filtration rates.

Tacrolimus is associated with a lower incidence of hypertension and hypercholesterolaemia than cyclosporin, but a higher incidence of diarrhoea, disturbances in glucose metabolism and some types of neurotoxicity. In addition, tacrolimus is only rarely associated with the cyclosporin-specific adverse effects hirsutism, gum hyperplasia and gingivitis, but it may cause alopecia and pruritus. Virtually all patients receiving a calcineurin inhibitor experienced at least one treatment-emergent adverse event. Many adverse events are dose dependent and respond to dosage reduction.

Post-transplant diabetes mellitus (PTDM) is one of the more serious metabolic disorders associated with calcineurin inhibitor treatment. In general, recent large clinical trials have revealed no between-group difference in the incidence of PTDM with tacrolimus treatment and cyclosporin microemulsion treatment.

Several studies have demonstrated that serum lipid profiles and the cardiovascular risk profile were affected less by tacrolimus than by cyclosporin, with tacrolimus recipients experiencing lower serum total cholesterol and triglyceride levels, and higher high density lipoprotein cholesterol levels. Mild to moderate hypertension has been documented in up to 50% of transplant recipients receiving tacrolimus-based immunosuppression and has usually been managed effectively with antihypertensive agents.

All immunosuppressive agents also increase the risk of developing malignancy, particularly lymphoma and malignancy of the skin. The incidence of Epstein-Barr virus-related post-transplant lymphoproliferative disorder (PTLD) in adult transplant recipients receiving tacrolimus therapy is typically less than 2% and appears to be similar to that in cyclosporin recipients, although the incidence in paediatric liver transplant recipients may be higher with tacrolimus treatment than with cyclosporin therapy. However, this finding may have been a result of the significantly higher mortality rate at 3 years post-transplantation in the cyclosporin than in the tacrolimus group (32% vs 15%; p < 0.05).

The risks of tacrolimus treatment during pregnancy appear to be no greater than those associated with cyclosporin microemulsion treatment.

Pharmacoeconomic Issues

Pharmacoeconomic studies post-transplantation demonstrated a cost advantage for tacrolimus-based immunosuppression compared with cyclosporin microemulsion-based immunosuppression as a result of a lower rate of acute rejection in patients treated with tacrolimus.

In renal transplant recipients, intent-to-treat cost-effectiveness analyses of direct medical costs, from a randomised prospective trial over a period of 2.7 years and in two retrospective analyses of 6-month data, demonstrated that tacrolimus-based therapy was more cost effective than cyclosporin-based therapy. In all analyses, the higher acquisition cost of tacrolimus was more than offset by the costs associated with the higher rate of acute rejection in the cyclosporin groups. For example, in the randomised study the rate of acute rejection was 13% in the tacrolimus group and 24% in the cyclosporin group. Although the total average cost per patient was higher with tacrolimus treatment, better clinical outcomes associated with tacrolimus led to more favourable cost effectiveness compared with cyclosporin in terms of cost per survivor (£20 033 vs £20 374), cost per patient with a functioning graft (£21 555 vs £22 670) and cost per patient with a rejection-free graft (£29 359 vs £34 246). Year of costings was not reported.

A cost-minimisation analysis of a 6-month study demonstrated cost differences between the two treatment groups in favour of tacrolimus for total cost per patient (€1776), cost per survivor with a functioning graft (€2305) and cost per survivor (€1892). In a sensitivity analysis, the cost advantage for tacrolimus over cyclosporin was maintained when the unit costs of the main cost drivers were varied (e.g. hospitalisation and study drug by ±50% and concomitant medication by ±25%). These costs were based on an Italian hospital perspective, with the year of costings not reported.

In liver transplant recipients, a 6-month cost analysis demonstrated a lower total cost of rejection and drugs in the tacrolimus group compared with the cyclosporin group ($US434 300 vs $US1 305 300 for every 100 patients).

Dosage and Administration

Tacrolimus is indicated for primary immunosuppressive therapy following kidney and liver transplantation in greater than 60 countries and for heart transplantation in some of these countries; it is also approved as rescue therapy for a variety of solid solid organ transplants in more than 60 countries.

Tacrolimus should be taken orally in two divided doses at intervals of 12 hours. Administration via continuous intravenous infusion carries the risk of anaphylaxis, but may be used in the short term if oral therapy is not possible. When switching from intravenous to oral therapy, the first oral dose should be administered 8–12 hours after discontinuing the infusion.

The first dose of tacrolimus should be given no sooner than 6 hours after liver transplantation and within 24 hours of kidney transplantation. The recommended starting dosage of oral tacrolimus in adults ranges from approximately 0.1–0.3 mg/kg/day. The dose may be reduced during maintenance therapy, and should be titrated based on clinical assessments of rejection and tolerability for each patient.

Children generally require higher doses (on a milligram per kilogram basis) than adults to achieve similar whole-blood concentrations of tacrolimus. Low dosages are recommended in patients with renal or hepatic dysfunction. Tacrolimus may be given as rescue therapy, but should not be initiated until approximately 24 hours after the discontinuation of cyclosporin.

It is recommended that tacrolimus be taken on an empty stomach to maximise absorption. Trough whole-blood tacrolimus concentrations should be monitored and, generally, should be maintained below 20 μg/L.


Tacrolimus Liver Transplant Recipient Bronchiolitis Obliterans Syndrome Acute Rejection Episode Cyclosporin Microemulsion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Kahan BD, Koch SM. Current immunosuppressant regimens: considerations for critical care. Curr Opin Crit Care 2001 Aug; 7(4): 242–50PubMedCrossRefGoogle Scholar
  2. 2.
    Gaston RS. Maintenance immunosuppression in the renal transplant recipient: an overview. Am J Kidney Dis 2001 Dec; 38 (6 Suppl. 6): S25–35PubMedCrossRefGoogle Scholar
  3. 3.
    Peters DH, Fitton A, Plosker GL, et al. Tacrolimus: a review of its pharmacology, and therapeutic potential in hepatic and renal transplantation. Drugs 1993; 46(4): 746–94PubMedCrossRefGoogle Scholar
  4. 4.
    Spencer CM, Goa KL, Gillis JC. Tacrolimus: an update of its pharmacology and clinical efficacy in the management of organ transplantation. Drugs 1997; 54(6): 925–75PubMedCrossRefGoogle Scholar
  5. 5.
    Plosker GL, Foster RH. Tacrolimus: a further update of its pharmacology and therapeutic use in the management of organ transplantation. Drugs 2000 Feb; 59(2): 323–89PubMedCrossRefGoogle Scholar
  6. 6.
    Sharkey J, Jones PA, McCarter JF, et al. Calcineurin inhibitors as neuroprotectants: focus of tacrolimus and cyclosporin. CNS Drugs 2000; 13(1): 1–13CrossRefGoogle Scholar
  7. 7.
    Jiang H, Yang X, Soriano RN, et al. Distinct patterns of cytokine gene suppression by the equivalent effective doses of cyclosporine and tacrolimus in rat heart allografts. Immunobiology 2000 Sep; 202(3): 280–92PubMedCrossRefGoogle Scholar
  8. 8.
    Egi H, Hayamizu K, Kitayama T, et al. Downregulation of both interleukin-12 and interleukin-2 in heart allografts by pretransplant host treatment with granulocyte colony-stimulating factor and tacrolimus. Cytokine 2002 May 7; 18(3): 164–7PubMedCrossRefGoogle Scholar
  9. 9.
    Zipperle S, Weimer R, Golling M, et al. Impaired T-cell IL-10 secretion and CD4 helper function in liver transplant patients. Transplan Proc 1997; 29: 1079–80CrossRefGoogle Scholar
  10. 10.
    Jiang H, Wynn C, Pan F, et al. Tacrolimus and cyclosporine differ in their capacity to overcome ongoing allograft rejection as a result of their differential abilities to inhibit interleukin-10 production. Transplantation 2002 Jun 15; 73(11): 1808–17PubMedCrossRefGoogle Scholar
  11. 11.
    Ebbs A, Pan F, Wynn C, et al. Tacrolimus treats ongoing allograft rejection by inhibiting interleukin-10 mediated functional cytotoxic cell infiltration. Transplant Proc 2002; 34(5): 1378–81PubMedCrossRefGoogle Scholar
  12. 12.
    Jiang H, Yang XF, Wynn C, et al. IL-10: a tacrolimus-specific cytotoxic mediator in ongoing allograft rejection. Transplant Proc 2001; 33(l–2): 510–3PubMedCrossRefGoogle Scholar
  13. 13.
    Jiang H, Kobayashi M. Differences between cyclosporin A and tacrolimus in organ transplantation. Transplant Proc 1999; 31: 1978–80PubMedCrossRefGoogle Scholar
  14. 14.
    Hämäläinen M, Lahti A, Moilanen E. Calcineurin inhibitors, cyclosporin A and tacrolimus inhibit expression of inducible nitric oxide synthase in colon epithelial and macrophage cell lines. Eur J Pharmacol 2002; 448(2–3): 239–44PubMedCrossRefGoogle Scholar
  15. 15.
    Kaibori M, Sakitani K, Oda M, et al. Immunosuppressant FK506 inhibits inducible nitric oxide synthase gene expression at a step of the NK-κB activation in rat hepatocytes. J Hepatol 1999; 30: 1138–45PubMedCrossRefGoogle Scholar
  16. 16.
    Migita K, Tanaka H, Okamoto K, et al. FK506 augments glucocorticoid-mediated cyclooxygenase-2 down-regulation in human rheumatoid synovial fibroblasts. Lab Invest 2000; 80(2): 135–41PubMedCrossRefGoogle Scholar
  17. 17.
    Migita K, Origuchi T, Kawabe Y, et al. FK506 markedly enhances apoptosis of antigen-stimulated peripheral T cells by down-regulation of Bcl-xl. Transplantation 1999; 68(7): 1018–23PubMedCrossRefGoogle Scholar
  18. 18.
    Lang P, Baron C. Molecular mechanisms of immunosuppressive chemical agents recently introduced in clinical transplantation protocols. Ther Drug Monitor 1995; 17: 584–91CrossRefGoogle Scholar
  19. 19.
    Trimarchi HM, Truong LD, Brennan S, et al. FK506-associated thrombotic microangiopathy. Transplantation 1999; 67: 539–44PubMedCrossRefGoogle Scholar
  20. 20.
    Mor E, Yussim A, Chodoff L, et al. New immunosuppressive agents for maintenance therapy in organ transplantation: focus on adverse effects. Biodrugs 1997; 8: 469–88PubMedCrossRefGoogle Scholar
  21. 21.
    Bicknell GR, Williams ST, Shaw JA, et al. Differential effects of cyclosporin and tacrolimus on the expression of fibrosis-associated genes in isolated glomeruli from renal transplants. Br J Surg 2000 Nov; 87(11): 1569–75PubMedCrossRefGoogle Scholar
  22. 22.
    Knoflach A, Zhongning G, Binswanger U. Transforming growth factor-β1 gene expression in patients with stable renal allograft function and chronic renal allograft dysfunction: differences between cyclosporine (CYA) or tacrolimus (FK) based immunosuppression [abstract]. Nephrol Dial Transplant 2001; 16: A202Google Scholar
  23. 23.
    Klein IHHT, Abrahams A, van Ede T, et al. Different effects of tacrolimus and cyclosporine on renal hemodynamics and blood pressure in healthy subjects. Transplantation 2002; 73(5): 732–6PubMedCrossRefGoogle Scholar
  24. 24.
    Mohamed MA, Burt AD, Robertson H, et al. TGF-beta expression in protocol transplant liver biopsies: a comparative study between cyclosporine-A (CyA) and tacrolimus (FK 506) immunosuppression. Transplant Proc 2001; 33(1–2): 1378–80PubMedCrossRefGoogle Scholar
  25. 25.
    Jain S, Bicknell GR, Nicholson ML. Tacrolimus has less fibrogenic potential than cyclosporin A in a model of renal ischaemia-reperfusion injury. Br J Surg 2000 Nov; 87(11): 1563–8PubMedCrossRefGoogle Scholar
  26. 26.
    Baboolal K, Jones GA, Janezic A, et al. Molecular and structural consequences of early allograft injury. Kid Inter 2002; 61: 686–96CrossRefGoogle Scholar
  27. 27.
    Fernández LA, Lehmann R, Luzi L, et al. The effects of maintenance doses of FK506 versus cyclosporin A on glucose and lipid metabolism after orthotopic liver transplantation. Transplantation 1998; 68(10): 1532–41CrossRefGoogle Scholar
  28. 28.
    Jindal RM, Sidner RA, Milgrom ML. Post-transplant diabetes mellitus: the role of immunosuppression. Drug Saf 1997; 16(4): 242–57PubMedCrossRefGoogle Scholar
  29. 29.
    Kochi S, Takanaga H, Matsuo H, et al. Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus. Life Sci 2000; 66(23): 2255–60PubMedCrossRefGoogle Scholar
  30. 30.
    Jurcevic S, Dunn MJ, Crisp S, et al. A new enzyme-linked immunosorbent assay to measure anti-endothelial antibodies after cardiac transplantation demonstrates greater inhibition of antibody formation by tacrolimus compared with cyclosporine. Transplantation 1998; 65: 1197–202PubMedCrossRefGoogle Scholar
  31. 31.
    Weis M, Wildhirt SM, Schulze C, et al. Impact of immunosuppression on coronary endothelial function after cardiac transplantation. Transplant Proc 1998; 30: 871–2PubMedCrossRefGoogle Scholar
  32. 32.
    Chan MCY, Kwok BW, Shiba N, et al. Conversion of cyclosporine to tacrolimus for refractory or persistent myocardial rejection. Transplant Proc 2002; 34(5): 1850–2PubMedCrossRefGoogle Scholar
  33. 33.
    Kwok BW-K, Panchal SN, Hunt SA, et al. Long-term impact of tacrolimus switch on non-rejecting heart transplant [abstract]. 2nd International Congress on Immunosuppression; 2001 Dec 6–8; San Diego (CA), 65Google Scholar
  34. 34.
    van Riemsdijk IC, Vantrimpont PJ, Balk AH, et al. Conversion from cyclosporine to tacrolimus benefits heart transplant recipients and allows a significant dose-reduction of MMF [abstract]. Am J Transplant 2001; 1 Suppl. 1: 322Google Scholar
  35. 35.
    Kohnle M, Zimmermann U, Lütkes P, et al. Conversion from cyclosporine A to tacrolimus after kidney transplantation due to hyperlipidemia. Transpl Int 2000; 13 Suppl. 1: S345–8PubMedCrossRefGoogle Scholar
  36. 36.
    Manzarbeitia C, Reich DJ, Rothstein KD, et al. Tacrolimus conversion improves hyperlipidemic states in stable liver transplant recipients. Liver Transpl 2001 Feb; 7(2): 93–9PubMedCrossRefGoogle Scholar
  37. 37.
    Manu M, Tanabe K, Tokumoto T, et al. Impact of tacrolimus on hyperlipidemia after renal transplantation: a Japanese single center experience. Transplant Proc 2000 Nov; 32(7): 1736–8PubMedCrossRefGoogle Scholar
  38. 38.
    Schnitzler MA, Lowell JA, Brennan DC. New-onset post renal transplant hyperlipidemia with cyclosporine compared to tacrolimus [abstract]. 2nd International Congress on Immunosuppression; 2001 Dec 6–8; San Diego (CA), 121Google Scholar
  39. 39.
    Artz MA, Boots JMM, Ligtenberg G, et al. Randomized conversion from cyclosporine to tacrolimus in renal transplant patients: improved lipid profile and unchanged plasma homocysteine levels. Transplant Proc 2002; 34(5): 1793–4PubMedCrossRefGoogle Scholar
  40. 40.
    Aguirrezabalaga J, Fernandez-Selles C, Fraguela J, et al. Lipid profiles after liver transplantation in patients receiving tacrolimus or cyclosporin. Transplant Proc 2002 Aug; 34(5): 1551PubMedCrossRefGoogle Scholar
  41. 41.
    Kaibori M, Inoue T, Tu W, et al. FK506, but not cyclosporin A, prevents mitochondrial dysfunction during hypoxia in rat hepatocytes. Life Sci 2001 May 25; 69(1): 17–26PubMedCrossRefGoogle Scholar
  42. 42.
    Voggenreiter G, Assenmacher S, Kreuzfelder E, et al. Immunosuppression with FK506 increases bone induction in demineralized isogeneic and xenogeneic bone matrix in the rat. J Bone Miner Res 2000 Sep; 15(9): 1825–34PubMedCrossRefGoogle Scholar
  43. 43.
    Goffin E, Devogelaer J-P, Lalaoui A, et al. Tacrolimus and low-dose steroid immunosuppression preserves bone mass after renal transplantation. Transpl Int 2002 Mar; 15(2–3): 73–80PubMedCrossRefGoogle Scholar
  44. 44.
    El Haggan W, Barthe N, Vendrely B, et al. One year evolution of bone mineral density in kidney transplant recipients receiving tacrolimus versus cyclosporine. Transplant Proc 2002; 34(5): 1817–8PubMedCrossRefGoogle Scholar
  45. 45.
    Monegal A, Navasa M, Guañabens N, et al. Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A. Calcif Tissue Int 2001 Feb; 68(2): 83–6PubMedCrossRefGoogle Scholar
  46. 46.
    Goffin E, Devogelaer J-P, Depresseux G, et al. Evaluation of bone mineral density after renal transplantation under a tacrolimus-based immunosuppression: a pilot study. Clin Nephrol 2003 Mar; 59(3): 190–5PubMedGoogle Scholar
  47. 47.
    Tang L, Ebara S, Kawasaki S, et al. FK506 enhanced osteoblastic differentiation in mesenchymal cells. Cell Biol Int 2002; 26(1): 75–84PubMedCrossRefGoogle Scholar
  48. 48.
    Migita K, Eguchi K, Kawabe Y, et al. FK506 augments activation-induced programmed cell death of T lymphocytes in vivo. J Clin Invest 1995; 96: 727–32PubMedCrossRefGoogle Scholar
  49. 49.
    Migita K, Eguchi K, Kawabe Y, et al. FK506 potentiates steroid-induced T-cell apoptosis. Transplantation 1997; 64(9): 1365–9PubMedCrossRefGoogle Scholar
  50. 50.
    Jurewicz WA. Tacrolimus and ciclosporin microemulsion? A long-term comparison. XIX International Congress of the Transplantation Society satellite symposium on “Optimising long-term renal function”; 2002 Aug 27; Miami (FL), 5-6Google Scholar
  51. 51.
    Paul LC. Overview of side effects of immunosuppressive therapy. Transplant Proc 2001 May; 33(3): 2089–91PubMedCrossRefGoogle Scholar
  52. 52.
    Campistol JM, Grinyó JM. Exploring treatment options in renal transplantation: the problems of chronic allograft dysfunction and drug-related nephrotoxicity. Transplantation 2001 Jun 15; 71 (11 Suppl.): SS42–51PubMedGoogle Scholar
  53. 53.
    Van Gelder T. Drug interactions with tacrolimus. Drug Saf 2002; 25(10): 707–12PubMedCrossRefGoogle Scholar
  54. 54.
    Venkataramanan R, Swaminathan A, Prasad T, et al. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet 1995; 29(6): 404–30PubMedCrossRefGoogle Scholar
  55. 55.
    Wallemacq PE, Verbeeck RK. Comparative clinical pharmacokinetics of tacrolimus in paediatric and adult patients. Clin Pharmacokinet 2001; 40(4): 283–95PubMedCrossRefGoogle Scholar
  56. 56.
    Christians U, Jacobsen W, Benet LZ, et al. Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clin Pharmacokinet 2002; 41(11): 813–51PubMedCrossRefGoogle Scholar
  57. 57.
    Fujisawa Healthcare Inc. Prograf prescribing information (US) [online]. Available from URL: [Accessed 2002 Nov 12]
  58. 58.
    Jörgensen K, Povlsen J, Madsen S, et al. C2 (2-h) levels are not superior to trough levels as estimates of the area under the curve in tacrolimus-treated renal-transplant patients. Nephrol Dial Transplant 2002 Aug; 17(8): 1487–90PubMedCrossRefGoogle Scholar
  59. 59.
    Jörgensen KA, Povlsen JV, Madsen S, et al. Two-hour blood tacrolimus levels are not superior to trough levels as estimates of the area under the curve in tacrolimus-treated renal transplant patients. Transplant Proc 2002; 34(5): 1721–2PubMedCrossRefGoogle Scholar
  60. 60.
    Undre NA. Pharmacokinetics of tacrolimus-based combination therapies. XIX International Congress of the Transplantation Society; 2002 Aug 27; Miami (FL), 7-9Google Scholar
  61. 61.
    Filler G, Feber J, Lepage N, et al. Universal approach to pharmacokinetic monitoring of immunosuppressive agents in children. Pediatr Transplant 2002; 6: 411–8PubMedCrossRefGoogle Scholar
  62. 62.
    Braun F, Schütz E, Peters B, et al. Pharmacokinetics of tacrolimus primary immunosuppression in kidney transplant recipients. Transplant Proc 2001 May; 33(3): 2127–8PubMedCrossRefGoogle Scholar
  63. 63.
    Braun F, Peters B, Schütz E, et al. Therapeutic drug monitoring of tacrolimus early after liver transplantation. Transplant Proc 2002 Aug; 34(5): 1538–9PubMedCrossRefGoogle Scholar
  64. 64.
    Belitsky P, Dunn S, Johnston A, et al. Impact of absorption profiling on efficacy and safety of cyclosporin therapy in transplant recipients. Clin Pharmacokinet 2000; 39(2): 117–25PubMedCrossRefGoogle Scholar
  65. 65.
    Barakat O, Peaston R, Rai R, et al. Clinical benefit of monitoring cyclsoporine C2 and C4 in long-term in liver transplant recipients. Transplant Proc 2002; 34: 1535–7PubMedCrossRefGoogle Scholar
  66. 66.
    Fujisawa Ltd. Prograf (tacrolimus): summary of product characteristics (UK). Fujisawa Ltd, 1999Google Scholar
  67. 67.
    Bekersky I, Dressier D, Mekki Q. Effect of time of meal consumption on bioavailability of a single oral 5 mg tacrolimus dose. J Clin Pharmacol 2001 Mar; 41(3): 289–97PubMedCrossRefGoogle Scholar
  68. 68.
    Bekersky I, Dressier D, Mekki QA. Effect of low- and high-fat meals on tacrolimus absorption following 5 mg single oral doses to healthy human subjects. J Clin Pharmacol 2001; 41(2): 176–82PubMedCrossRefGoogle Scholar
  69. 69.
    Mancinelli LM, Frassetto L, Floren LC, et al. The pharmacokinetics and metabolic disposition of tacrolimus: a comparison across ethnic groups. Clin Pharmac Ther 2001; 69(1): 24–31CrossRefGoogle Scholar
  70. 70.
    Honaker MR, Duhart Jr BT. Tacrolimus: a ‘heads up’ on potential drug interactions. J Crit Illn 2002; 17(4): 141–2Google Scholar
  71. 71.
    Hebert MF, Fisher RM, Marsh CL, et al. Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 1999; 39: 91–6PubMedCrossRefGoogle Scholar
  72. 72.
    Zimmerman JJ, Patat A, Souan ML, et al. Potential pharmacokinetic interactions between sirolimus and tacrolimus [abstract]. Am J Transplant 2001; 1 Suppl. 1: 384Google Scholar
  73. 73.
    Mathis S, Shah N, Friedman GS, et al. Pharmacokinetic interaction of chloramphenicol with calcineurin inhibitors [abstract]. Am J Transplant 2001; 1 Suppl. 1: 140Google Scholar
  74. 74.
    Vasquez E, Pollak R, Benedetti E. Clotrimazole increases tacrolimus blood levels: a drug interaction in kidney transplant patients. Clin Transplant 2001 Apr; 15(2): 95–9PubMedCrossRefGoogle Scholar
  75. 75.
    Toda F, Tanabe K, Ito S, et al. Tacrolimus trough level adjustment after administration of fluconazole to kidney recipients. Transplant Proc 2002; 34(5): 1733–5PubMedCrossRefGoogle Scholar
  76. 76.
    Sifontis NM, Benedetti E, Vasquez EM. Clinically significant drug interaction between basiliximab and tacrolimus in renal transplant recipients. Transplant Proc 2002; 34(5): 1730–2PubMedCrossRefGoogle Scholar
  77. 77.
    Pirsch J, Bekersky I, Vincenti F, et al. Coadministration of tacrolimus and mycophenolate mofetil in stable kidney transplant patients: pharmacokinetics and tolerability. J Clin Pharmacol 2000 May; 40(5): 527–32PubMedCrossRefGoogle Scholar
  78. 78.
    McAlister VC, Mahalati K, Peltekian KM, et al. A clinical pharmacokinetic study of tacrolimus and sirolimus combination immunosuppression comparing simultaneous to separated administration. Ther Drug Monit 2002 Jun; 24(3): 346–50PubMedCrossRefGoogle Scholar
  79. 79.
    Jain A, Venkataramanan R, Shapiro R, et al. Interaction between tacrolimus and antiretroviral agents in human immunodeficiency virus-positive liver and kidney transplantation patients. Transplant Proc 2002 Aug; 34(5): 1540–1PubMedCrossRefGoogle Scholar
  80. 80.
    Jones TE, Morris RG. Pharmacokinetic interaction between tacrolimus and diltiazem: dose-response relationship in kidney and liver transplant recipients. Clin Pharmacokinet 2002; 41(5): 381–8PubMedCrossRefGoogle Scholar
  81. 81.
    Leather HL, Wingard JR. Characterizing the pharmacokinetic drug (PK) interaction between intravenous (IV) itraconazole (Itra) and IV tacrolimus or IV cyclosporin (Cya) in allogeneic bone marrow transplant (Allobmt) patients [abstract]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22; Chicago (IL), 5Google Scholar
  82. 82.
    Banerjee R, Leaver N, Lyster H, et al. Coadministration of itraconazole and tacrolimus after thoracic organ transplantation. Transplant Proc 2001; 33(1–2): 1600–2PubMedCrossRefGoogle Scholar
  83. 83.
    Hebert MF, Park JM, Chen Y-L, et al. Effects of St. John’s wort on tacrolimus pharmacokinetics in healthy volunteers [abstract no. 150]. Pharmacotherapy 2003; 23(3): 414Google Scholar
  84. 84.
    Undre NA, van Hooff J, Christianns M, et al. Pharmacokinetics of FK 506 and mycophenolic acid after the administration of a FK 506-based regimen in combination with mycophenolate mofetil in kidney transplantation. Transplant Proc 1998; 30: 1299–302PubMedCrossRefGoogle Scholar
  85. 85.
    Osowski CL, Dix SP, Lin LS, et al. Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients. Transplantation 1996; 61(6): 1268–72PubMedCrossRefGoogle Scholar
  86. 86.
    Ahsan N, Johnson C, Gonwa T, et al. Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years. Transplantation 2001 Jul 27; 72(2): 245–50PubMedCrossRefGoogle Scholar
  87. 87.
    Halloran P, Ahsan N, Johnson C, et al. 3 year followup of randomized multicenter kidney transplant study comparing tacrolimus (TAC) + azathioprine (AZA) vs cyclosporine modified (CSA) + mycophenolate mofetil (MMF) vs TAC+MMF. Am J Transplant 2001; 1 Suppl. 1: 405CrossRefGoogle Scholar
  88. 88.
    Johnson C, Ahsan N, Gonwa T, et al. Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation 2000 Mar 15; 69(5): 834–41PubMedCrossRefGoogle Scholar
  89. 89.
    Montagnino G, Krämer B, Arias M. Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in kidney transplantation: twelve-month follow-up. European Tacrolimus vs Cyclosporin Microemulsion Renal Transplantation Study Group. Transplant Proc 2002 Aug; 34(5): 1635–7Google Scholar
  90. 90.
    Sperschneider H. A large, multicentre trial to compare the efficacy and safety of tacrolimus with cyclosporine microemulsion following renal transplantation. European Renal Transplantation Study Group. Transplant Proc 2001; 33(1–2): 1279–81PubMedCrossRefGoogle Scholar
  91. 91.
    Margreiter R. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. European Tacrolimus vs Ciclosporin Microemulsion Renal Transplantation Study Group. Lancet 2002 Mar 2; 359(9308): 741–6Google Scholar
  92. 92.
    Del Castillo D. Analysis of primary and recurrent rejection following renal transplantation in a large, comparative, multi-centre trial. European Tacrolimus vs Cyclosporin-Microemulsion (CyA-ME) Renal Transplantation Study Group. Transplant Proc 2001; 33(1–2): 1259–61PubMedCrossRefGoogle Scholar
  93. 93.
    Ruiz San Millan JC, Arias M, Kraemer BK, et al. Tacrolimus versus ciclosporin-microemulsion in renal transplantation: the two year follow-up results [abstract no. 138]. Transplantation 2002; 74 Suppl.: 59Google Scholar
  94. 94.
    Chang R-WS, Snowden S, Palmer A, et al. European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients. Transpl Int 2001 Dec; 14(6): 384–90PubMedCrossRefGoogle Scholar
  95. 95.
    Calconi G, Vianello A. One-year follow-up of a large European trial comparing dual versus triple tacrolimus-based immunosuppressive regimens following renal transplantation. Italian and Spanish Tacrolimus Study Group. Transplant Proc 2001; 33(1–2): 1021–4PubMedCrossRefGoogle Scholar
  96. 96.
    Segoloni G, Bonomini V, Maresca MC, et al. Tacrolimus is highly effective in both dual and triple therapy regimens following renal transplantation. Spanish and Italian Tacrolimus Study Group. Transpl Int 2000; 13 Suppl. 1: S336–40PubMedCrossRefGoogle Scholar
  97. 97.
    Pascual J, Ortuno J. Simple tacrolimus-based immunosuppressive regimens following renal transplantation: a large multicenter comparison between double and triple therapy. Spanish and Italian Tacrolimus Study Group. Transplant Proc 2002 Feb; 34(1): 89–91Google Scholar
  98. 98.
    Garcia I. Efficacy and safety of dual versus triple tacrolimusbased therapy in kidney transplantation: two-year follow-up. Transplant Proc 2002 Aug; 34(5): 1638–9PubMedCrossRefGoogle Scholar
  99. 99.
    Cabello M. Three year follow-up of a large multicentre European trial comparing tacrolimus-based dual and tacrolimus-based triple immunosuppressive therapies in renal transplantation. Spanish-Italian Tacrolimus Renal Transplantation Study Group [abstract]. Transplantation 2002; 74 Suppl.: 428Google Scholar
  100. 100.
    Squifflet JP, Backman L, Claesson K, et al. Dose optimization of mycophenolate mofetil when administered with a low dose of tacrolimus in cadaveric renal transplant recipients. Transplantation 2001 Jul 15; 72(1): 63–9PubMedCrossRefGoogle Scholar
  101. 101.
    Meier-Kriesche H-U, Kaplan B. Cyclosporine microemulsion and tacrolimus are associated with decreased chronic allograft failure and improved long-term graft survival as compared with sandimmune. Am J Transplant 2002 Jan; 2(1): 100–4CrossRefGoogle Scholar
  102. 102.
    First MR. Importance of renal function for long-term outcomes. XIX International Congress of the Transplantation Society Satellite symposium on “Optimising long-term renal function”; 2002 Aug 27; Miami (FL), 3-4Google Scholar
  103. 103.
    Yang HC. Tailoring tacrolimus-based immunotherapy. XIX International Congress of the Transplantation Society satellite symposium on “Optimising long-term renal function”; 2002 Aug 27; Miami (FL), 11-2Google Scholar
  104. 104.
    Pascual M, Thieruvath T, Kawai T, et al. Strategies to improve long-term outcomes after renal transplantation. N Engl J Med 2002; 346(8): 580–90PubMedCrossRefGoogle Scholar
  105. 105.
    Fitzsimmons WE, Thompson D, Hariharan S, et al. Serum creatinine as a surrogate endpoint for graft loss in kidney transplantation: validation efforts from multicenter trials [abstract no. 533]. Am J Transplant 2002; 2 Suppl. 3: 272Google Scholar
  106. 106.
    Filler G, Browne R, Seikaly MG. Glomerular filtration rate as a putative ‘surrogate end-point’ for renal transplant clinical trials in children. Pediatr Transplant 2003; 7: 18–24PubMedCrossRefGoogle Scholar
  107. 107.
    Vincenti F, Jensik SC, Filo RS, et al. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation 2002 Mar 15; 73(5): 775–82PubMedCrossRefGoogle Scholar
  108. 108.
    Vincenti F. Tacrolimus (FK 506) in kidney transplantation: five-year survival results of the U.S. multicenter, randomized, comparative trial. Tacrolimus Kidney Transplant Study Group. Transplant Proc 2001; 33(1–2): 1019–20PubMedCrossRefGoogle Scholar
  109. 109.
    Mayer AD. Chronic rejection and graft half-life: five-year follow-up of the European Tacrolimus Multicenter Renal Study. Transplant Proc 2002; 34(5): 1491–2PubMedCrossRefGoogle Scholar
  110. 110.
    Bechstein W-O, Paczek L. A phase II, open-label, concentration-controlled, randomized 6-month study of standard-dose tacrolimus + sirolimus + corticosteroids compared to reduced-dose tacrolimus + sirolimus + corticosteroids in renal allograft recipients. European Rapamune-FK Study Group [abstract no. 1321]. Am J Transplant 2002; 2 Suppl. 3: 471Google Scholar
  111. 111.
    Daloze P, Whelchel, Cockfield S, et al. A 6-month multicenter randomized concentration-controlled study of reduced-dose tacrolimus (TAC) + sirolimus (SRL) + corticosteroids (CS) compared to standard-dose TAC + SRL + CS in clinical kidney transplantation [abstract no. 555]. Am J Transplant 2002; 2 Suppl. 3: 188Google Scholar
  112. 112.
    Yang H, Gonwa T, Rice K, et al. Sirolimus vs mycophenolate mofetil —results of the first U.S. multicenter kidney transplant study with tacrolimus combination therapy [abstract no. 557]. Transplantation 2002 Aug 27; 74 Suppl.: 188–9CrossRefGoogle Scholar
  113. 113.
    Wlodarczyk Z, vanHooff JP, Vanrenterghem Y, et al. Tacrolimus in combination with various dosages of rapamycin in renal recipients: safety and efficacy of the first 6-month multicenter randomised trial [abstract no. 554]. Transplantation 2002; 74 Suppl.: 187Google Scholar
  114. 114.
    Miller J, Burke GW, Ciancio G, et al. Randomized trial of three different immunosuppressive regimens to prevent chronic renal allograft rejection [abstract no. 0168]. Transplantation 2002 Aug 27; 74 Suppl.: 69Google Scholar
  115. 115.
    US Food and Drug Administration. 2003 Safety alert —rapamune (sirolimus) [online]. Available from URL: [Accessed 2003 Mar 20]
  116. 116.
    Wlodarczyk Z, Walaszewski J, Perner F. Freedom from rejection and stable kidney function are excellent criteria for steroid withdrawal in tacrolimus-treated kidney transplant recipients. Ann Transplant 2002; 7(3): 28–31PubMedGoogle Scholar
  117. 117.
    Squifflet J-P, Vanrenterghem Y, van Hooff JP, et al. Safe withdrawal of corticosteroids or mycophenolate mofetil: results of a large, prospective, multicenter, randomized study. Transplant Proc 2002 Aug; 34: 1584–6PubMedCrossRefGoogle Scholar
  118. 118.
    Sola E, Alférez MJ, Cabello M, et al. Low-dose and rapid steroid withdrawal in renal transplant patients treated with tacrolimus and mycophenolate mofetil. Transplant Proc 2002; 34(5): 1689–90PubMedCrossRefGoogle Scholar
  119. 119.
    Citterio F, Rigotti P, Scata MC, et al. Steroid withdrawal from tacrolimus-based therapy in renal transplant patients. Transplant Proc 2002; 34(5): 1707–8PubMedCrossRefGoogle Scholar
  120. 120.
    Boots JMM, Christianns MHL, van Duijhoven EM, et al. Early steroid withdrawal in renal transplantation with tacrolimus dual therapy: a pilot study. Transplantation 2002; 74(12): 1703–9PubMedCrossRefGoogle Scholar
  121. 121.
    Charpentier B. A three arm study comparing immediate tacrolimus therapy with ATG induction therapy followed by either tacrolimus or cyclosporine in adult renal transplant recipients. European Tacrolimus vs Microemulsified Cyclosporin Study Group. Transplant Proc 2002; 34(5): 1625–6Google Scholar
  122. 122.
    Mourad G, Garrigue V, Squifflet J-P, et al. Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression. Transplantation 2001 Sep 27; 72(6): 1050–5PubMedCrossRefGoogle Scholar
  123. 123.
    Charpentier B. Induction versus non-induction protocols in anti-calcineurin-based immunosuppression. Transplant Proc 2001 Nov-2001 31; 33(7–8): 3334–6PubMedCrossRefGoogle Scholar
  124. 124.
    Dudley CRK. Conversion at first rejection: a prospective trial comparing cyclosporine microemulsion with tacrolimus in renal transplant recipients. Transplant Proc 2001 Feb-2001 31; 33(1–2): 1034–5PubMedCrossRefGoogle Scholar
  125. 125.
    Pohanka E, Margreiter R, Sparacino V, et al. Switch to tacrolimus-based therapy for ciclosporin-related side effects: a large, prospective European study [abstract no. 2100]. Transplantation 2002; 74 Suppl.: 425–6Google Scholar
  126. 126.
    Filler G, Trompeter R, Webb NJA, et al. One-year glomerular filtration rate predicts graft survival in pediatric renal recipients: a randomized trial of tacrolimus vs cyclosporine microemulsion. Transplant Proc 2002; 34(5): 1935–8PubMedCrossRefGoogle Scholar
  127. 127.
    Trompeter R, Filler G, Webb NJ, et al. Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation. Pediatr Nephrol 2002 Mar; 17(3): 141–9PubMedCrossRefGoogle Scholar
  128. 128.
    Garcia CD, Schneider L, Barros VR, et al. Pediatric renal transplantation under tacrolimus or cyclosporine immuno-suppression and basiliximab induction. Transplant Proc 2002 Nov; 34(7): 2533–4PubMedCrossRefGoogle Scholar
  129. 129.
    Hasegawa A, Takahashi K, Ito K, et al. Optimal use of tacrolimus in living donor renal transplantation in children. Transplant Proc 2002 Aug; 34(5): 1939–41PubMedCrossRefGoogle Scholar
  130. 130.
    Palti G, Morvan S. Initial experience with tacrolimus in pediatric renal transplantation [abstract]. Transplantation 2002; 74 Suppl.: 492Google Scholar
  131. 131.
    Pape L, Henne T, Strehlau J, et al. Long-term stable glomerular filtration rate achieved with tacrolimus in pediatric renal transplantation. Transplant Proc 2002 Sep; 34(6): 2211PubMedCrossRefGoogle Scholar
  132. 132.
    Sarwal MM, Yorgin PD, Alexander S, et al. Promising early outcomes with a novel, complete steroid avoidance immuno-suppression protocol in pediatric renal transplantation. Transplantation 2001 Jul 15; 72(1): 13–21PubMedCrossRefGoogle Scholar
  133. 133.
    Suzart K, Ciancio G, Burke GW, et al. The use of daclizumab in pediatric first renal transplant recipients in combination with tacrolimus and mycophenolate mofetil [abstract]. Transplantation 2002; 74: 493–4Google Scholar
  134. 134.
    Ferraresso M, Ghio L, Edefonti A, et al. Conversion from cyclosporine to tacrolimus for refractory acute rejection in pediatric kidney transplant recipients: a single-center experience. Transplant Proc 2001; 33(7–8): 3590–1PubMedCrossRefGoogle Scholar
  135. 135.
    Ferraresso M, Ghio L, Edefonti A, et al. Conversion from cyclosporine to tacrolimus in pediatric kidney transplant recipients. Pediatr Nephrol 2002 Aug; 17: 664–7PubMedCrossRefGoogle Scholar
  136. 136.
    Hymes LC, Warshaw BL. Tacrolimus rescue therapy for children with acute renal transplant rejection. Pediatr Nephrol 2001 Dec; 16(12): 990–2PubMedCrossRefGoogle Scholar
  137. 137.
    Flynn JT, Bunchman TE, Sherbotie JR. Indications, results, and complications of tacrolimus conversion in pediatric renal transplantation. Pediatr Transplant 2001 Dec; 5(6): 439–46PubMedCrossRefGoogle Scholar
  138. 138.
    Reimer J, Franke GH, Philipp T, et al. Quality of life in kidney recipients: comparison of tacrolimus and cyclosporine-micro-emulsion. Clin Transplant 2002 Feb; 16(1): 48–54PubMedCrossRefGoogle Scholar
  139. 139.
    Reimer J, Franke GH, Luetkes P, et al. Quality of life after kidney transplantation —the impact of tacrolimus. Transplant Proc 2001 Feb-2001 31; 33(1–2): 1924–6PubMedCrossRefGoogle Scholar
  140. 140.
    Moons P, Vanrenterghem Y, van Hooff JP, et al. Steroids may compromise quality of life of renal transplant recipients on a tacrolimus-based regimen. Transplant Proc 2002; 34(5): 1691–2PubMedCrossRefGoogle Scholar
  141. 141.
    Jain A, Demetris AJ, Kashyap R, et al. Does tacrolimus offer virtual freedom from chronic rejection after primary liver transplantation? Risk and prognostic factors in 1,048 liver transplantations with a mean follow-up of 6 years. Liver Transpi 2001 Jul; 7(7): 623–30CrossRefGoogle Scholar
  142. 142.
    Jonas S, Guckelberger O, Müller A, et al. Cyclosporine-based quadruple induction therapy versus tacrolimus-based dual immunosuppression after liver transplantation: ten-year follow-up. Transplant Proc 2002 Aug; 34(5): 1504–6PubMedCrossRefGoogle Scholar
  143. 143.
    Chen JW, Pehlivan M, Gunson BK, et al. Tacrolimus (FK506) versus cyclosporine A in primary orthotopic liver transplantation — a 10 year follow-up of a randomized cohort [abstract]. Am J Transplant 2002; 2 Suppl. 3: 197Google Scholar
  144. 144.
    Muhlbacher F, for the European Liver Transplantation Tacrolimus vs Cyclosporin Microemulsion Study Group. Tacrolimus versus cyclosporin microemulsion in liver transplantation: results of a 3-month study. Transplant Proc 2001 Feb-2001 31; 33(1–2): 1339–40PubMedCrossRefGoogle Scholar
  145. 145.
    Müehlbacher FF, for the European Liver Transplant Tacrolimus vs Cyclosporine Study Group. Tacrolimus versus cyclosporine-microemulsion in liver transplantation: results of one year follow up [abstract no. 263]. 10th Congress of the European Society of Organ Transplantation; 2001 Oct 6–11; LisbonGoogle Scholar
  146. 146.
    O’Grady JG, Burroughs A, Hardy P, et al. Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial. Lancet 2002 Oct 12; 360(9340): 1119–25PubMedCrossRefGoogle Scholar
  147. 147.
    Timmermann W, Erhard J, Lange R, et al. A randomised trial comparing the efficacy and safety of tacrolimus with microemulsified cyclosporine after liver transplantation. Transplant Proc 2002 Aug; 34(5): 1516–8PubMedCrossRefGoogle Scholar
  148. 148.
    Boillot O, Baulieux J, Wolf P, et al. Low rejection rates with tacrolimus-based dual and triple regimens following liver transplantation. Clin Transplant 2001 Jun; 15(3): 159–66PubMedCrossRefGoogle Scholar
  149. 149.
    Jain A, Kashyap R, Dodson F, et al. A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone and mycophenolate mofetil in primary adult liver transplantation: a single center report. Transplantation 2001 Sep 27; 72(6): 1091–7PubMedCrossRefGoogle Scholar
  150. 150.
    Jain A, Kashyap R, Kramer D, et al. Prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil: complete report on 350 primary adult liver transplantations. Transplant Proc 2001; 33(1–2): 1342–4PubMedCrossRefGoogle Scholar
  151. 151.
    Neuhaus P, Klupp J, Langrehr JM, et al. Quadruple tacrolimus-based induction therapy including azathioprine and ALG does not significantly improve outcome after liver transplantation when compared with standard induction with tacrolimus and steroids: results of a prospective, randomized trial. Transplantation 2000 Jun 15; 69(11): 2343–53PubMedCrossRefGoogle Scholar
  152. 152.
    Langrehr JM, Klupp J, Junge G, et al. Quadruple versus dual tacrolimus-based induction after liver transplantation: a prospective, randomized trial. Transplant Proc 2001 May; 33(3): 2330–1PubMedCrossRefGoogle Scholar
  153. 153.
    Langrehr JM, Klupp J, Pfitzmann R, et al. A prospective, randomized trial with quadruple versus dual tacrolimus-based induction after liver transplantation. Transplant Proc 2001; 33(1–2): 1520PubMedCrossRefGoogle Scholar
  154. 154.
    Salizzoni M, Cavallari A, Risaliti A, et al. Tacrolimus-based dual therapy is as efficacious and safe as the conventional tacrolimus-based triple therapy in liver transplantation. Transplant Proc 2001 May; 33(3): 2258–62PubMedCrossRefGoogle Scholar
  155. 155.
    Serrano J, Garcia González M, Gomez M, et al. Tacrolimus is effective in both dual and triple regimens after liver transplantation. Transplant Proc 2002 Aug; 34(5): 1529–30PubMedCrossRefGoogle Scholar
  156. 156.
    Loinaz C, Marin LM, González-Pinto I, et al. A single-centre experience with cyclosporine microemulsion versus tacrolimus in 100 randomized liver transplant recipients: midterm efficacy and safety. Transplant Proc 2001; 33(7–8): 3439–41PubMedCrossRefGoogle Scholar
  157. 157.
    Greig PD, Grant DR, Kneteman NM, et al. Early steroid withdrawal following liver transplantation: two-year follow-up [abstract]. Transplantation 2000 Apr 27; 69 Suppl.: 389CrossRefGoogle Scholar
  158. 158.
    Greig PD, Grant DR, Kneteman NR, et al. Long-term results of early steroid withdrawal following liver transplantation [abstract no. 1120]. Am J Transplant 2001; 1 Suppl. 1: 418Google Scholar
  159. 159.
    Selzner N, Durand F, Bernuau J, et al. Conversion from cyclosporine to FK506 in adult liver transplant recipients: a combined North American and European experience. Transplantation 2001 Sep 27; 72(6): 1061–5PubMedCrossRefGoogle Scholar
  160. 160.
    Saliba F, Reynes M, Karam V, et al. Outcome of liver transplantation recipients with steroid resistant rejection and biliary ductopenia after conversion from cyclosporine to tacrolimus [abstract]. 2nd International Congress on Immunosuppression; 2001 Dec 6–8; San Diego (CA), 83-4Google Scholar
  161. 161.
    Jain A, Mazariegos G, Kashyap R, et al. Comparative long-term evaluation of tacrolimus and cyclosporine in pediatric liver transplantation. Transplantation 2000 Aug 27; 70(4): 617–25PubMedCrossRefGoogle Scholar
  162. 162.
    Rodeck B, Kelly D, Jara P, et al. Tacrolimus dual therapy versus cyclosporin-microemulsion triple therapy in paediatric liver transplant recipients: results of a 12-month comparative study [abstract]. J Hepatol 2002 Apr; 36 Suppl. 1: 31CrossRefGoogle Scholar
  163. 163.
    Burdelsky M, Ganschow R, Kelly D, et al. Comparison of tacrolimus therapy with cyclosporin therapy in pediatric liver transplant recipients: results of a large, multicentre, randomized trial [abstract no. 0388]. Transplantation 2002 Aug 27; 74 Suppl.: 136Google Scholar
  164. 164.
    Otte JB, Redding R, Kelly D, et al. Tacrolimus dual therapy versus cyclosporin-microemulsion triple therapy in pediatric liver transplantation: results from a multicentre randomized trial [abstract no. 0442]. Transplantation 2002 Aug 27; 74 Suppl.: 153Google Scholar
  165. 165.
    Asensio M, Margarit C, Chavez R, et al. Induction with basiliximab reduces acute rejection in pediatric liver transplant patients treated with tacrolimus and steroids. Transplant Proc 2002; 34(5): 1970–1PubMedCrossRefGoogle Scholar
  166. 166.
    Fridell JA, Jain A, Biederman R, et al. Causes of mortality beyond one year following pediatric liver transplant under tacrolimus [abstract no. 625]. Am J Transplant 2002; 2 Suppl. 3: 295Google Scholar
  167. 167.
    Jain A, Mazariegos G, Pokharna R, et al. Almost total absence of chronic rejection in primary pediatric liver transplantation under tacrolimus. Transplant Proc 2002 Aug; 34(5): 1968–9PubMedCrossRefGoogle Scholar
  168. 168.
    Petz W, Spada M, Bertani A, et al. Tacrolimus plus basiliximab versus tacrolimus plus steroids in pediatric liver transplantation: a randomized trial. Transplantation 2002 Aug 27; 74 Suppl.: 721Google Scholar
  169. 169.
    Reyes J, Jain A, Mazariegos G, et al. Long-term results after conversion from cyclosporine to tacrolimus in pediatric liver transplantation for acute and chronic rejection. Transplantation 2000 Jun 27; 69(12): 2573–80PubMedCrossRefGoogle Scholar
  170. 170.
    Spada M, Corno V, Colledan M, et al. Rejection and tacrolimus conversion therapy in paediatric liver transplantation. Transpl Int2000; 13 Suppl. 1: S341–4PubMedCrossRefGoogle Scholar
  171. 171.
    Furlan V, Debray D, Fourre C, et al. Conversion from cyclosporin A to tacrolimus in pediatric liver transplantation. Pediatr Transplant 2000 Aug; 4(3): 207–10PubMedCrossRefGoogle Scholar
  172. 172.
    Grimm M, Rinaldi M, Yonan NA, et al. Efficacy and safety of tacrolimus (TAC) vs. cyclosporine microemulsion (CME) in de novo cardiac transplant recipients: 6-month results [abstract no. 56]. J Heart Lung Transplant 2003; 22 Suppl.: S92CrossRefGoogle Scholar
  173. 173.
    Mehra MR, Uber PA, Park MH, et al. A randomized comparison of an immunosuppressive strategy using tacrolimus and cyclosporine in black heart transplant recipients. Transplant Proc 2001; 33(1–2): 1606–7PubMedCrossRefGoogle Scholar
  174. 174.
    Mehra MR, Uber PA, Scott RL, et al. Racial differences in clinical outcome using tacrolimus and mycophenolate mofetil immunosuppression in heart transplantation. Transplant Proc 2001; 33(1–2): 1613–4PubMedCrossRefGoogle Scholar
  175. 175.
    Baran D, Galin I, Segura L, et al. Tacrolimus and cardiac transplantation: a comparison of monotherapy and steroid-dependent patients. Transplant Proc 2002 Aug; 34(5): 1845–6PubMedCrossRefGoogle Scholar
  176. 176.
    Teebken OE, Strüber M, Harringer W, et al. Primary immunosuppression with tacrolimus and mycophenolate mofetil versus cyclosporine and azathioprine in heart transplant recipients. Transplant Proc 2002; 34(4): 1265–8PubMedCrossRefGoogle Scholar
  177. 177.
    Meiser BM, Reichart B, Vigano M, et al. The first multicentre tacrolimus heart pilot study: three year follow-up [abstract]. Am J Transplant 2001; 1 Suppl. 1: 216Google Scholar
  178. 178.
    Meiser B, Groetzner J, Mueller M, et al. Trough level adjusted MMF after HTX: is it more efficacious in combination with tacrolimus or cyclosporine. Transplantation 2002 Aug 27; 74 Suppl.: 70Google Scholar
  179. 179.
    Steinbuchel NV, Limm H, Leopold C, et al. Assessment of health-related quality-of-life in patients after heart transplantation under therapy with tacrolimus or cyclosporine. Transpl Int 2000; 13 Suppl. 1: S609–14CrossRefGoogle Scholar
  180. 180.
    Keogh AM, Arnold RH, Macdonald PS, et al. A randomized trial of tacrolimus (FK506) versus total lymphoid irradiation for the control of repetitive rejection after cardiac transplantation. J Heart Lung Transplant 2001 Dec; 20(12): 1331–4PubMedCrossRefGoogle Scholar
  181. 181.
    Israni A, Brozena S, Pankewycz O, et al. Conversion to tacrolimus for the treatment of cyclosporine-associated nephrotoxicity in heart transplant recipients. Am J Kidney Dis 2002 Mar; 39(3): E16PubMedCrossRefGoogle Scholar
  182. 182.
    Crespo-Leiro MG, Paniagua MJ, Mosquera I, et al. Replacement of cyclosporine by tacrolimus for immunosuppression in heart transplant patients: safety and efficacy. Transplant Proc 2002 Feb; 34(1): 113–4PubMedCrossRefGoogle Scholar
  183. 183.
    De Bonis M, Reynolds L, Barros J, et al. Tacrolimus as a rescue immunosuppressant after heart transplantation. Eur J Cardiothorac Surg 2001 May; 19(5): 690–5PubMedCrossRefGoogle Scholar
  184. 184.
    Cairn J, Yek T, Banner NR, et al. Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome. J Heart Lung Transplant 2003 Jan; 22(1): 50–7PubMedCrossRefGoogle Scholar
  185. 185.
    Treede H, Klepetko W, Reichenspurner H, et al. Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols. J Heart Lung Transplant 2001 May; 20(5): 511–7PubMedCrossRefGoogle Scholar
  186. 186.
    McCurry KR, Zaldonis DB, Keenan RJ, et al. Long term follow-up of a prospective, randomized trial of tacrolimus versus cyclosporine in human lung transplantation [abstract]. Am J Transplant 2002; 2 Suppl. 3: 159Google Scholar
  187. 187.
    Zuckermann A, Reichenspurner H, Jaksch P, et al. Long term follow-up of a prospective randomized trial comparing tacrolimus versus cyclosporine in combination with MMF after lung transplantation [abstract no. 9]. J Heart Lung Transplant 2003; 22 Suppl.: S76–7CrossRefGoogle Scholar
  188. 188.
    Treede H, Reichenspurner H, Meiser B, et al. Influence of four different immunosuppressive protocols on acute and chronic rejection (BOS) after lung transplantation —experience in 120 patients. J Heart Lung Transplant 2001 Feb; 20: 176PubMedCrossRefGoogle Scholar
  189. 189.
    Roman A, Bravo C, Monforte V, et al. Preliminary results of rescue therapy with tacrolimus and mycophenolate mofetil in lung transplanted patients with bronchiolitis obliterans. Transplant Proc 2002 Feb; 34(1): 146–7PubMedCrossRefGoogle Scholar
  190. 190.
    Vitulo P, Oggionni T, Cascina A, et al. Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation. J Heart Lung Transplant 2002 Apr; 21(4): 435–9PubMedCrossRefGoogle Scholar
  191. 191.
    Fieguth H, Krueger S, Wiedenmann D, et al. Tacrolimus for treatment of Bronchiolitis Obliterans Syndrome after unilateral and bilateral lung transplantation. Transplant Proc 2002 Aug; 34(5): 1884PubMedCrossRefGoogle Scholar
  192. 192.
    Verleden GM, Buyse B, Delcroix M, et al. Changing cyclosporine (Cy) to tacrolimus (Tac) after lung transplantation (LTx): reasons and outcome [abstract]. Eur Respir J Suppl 2000 Aug; 16 Suppl. 31: 510Google Scholar
  193. 193.
    Klepetko W, Sarahrudi K, Corris P, et al. Efficacy of conversion from cyclosporin A to tacrolimus in lung transplantation [abstract no. 86]. Am J Transplant 2002; 2 Suppl. 3: 159Google Scholar
  194. 194.
    Land W, Malaise J, Sandberg J, et al. Tacrolimus versus cyclosporine in primary simultaneous pancreas-kidney transplantation: preliminary results at 1 year of a large multicenter trial. Transplant Proc 2002 Aug; 34(5): 1911–2PubMedCrossRefGoogle Scholar
  195. 195.
    Kaufman DB, Leventhal JR, Koffron A, et al. Simultaneous pancreas-kidney transplantation in the mycophenolate mofetil/ tacrolimus era: evolution from induction therapy with bladder drainage to noninduction therapy with enteric drainage. Surgery 2000 Oct; 128(4): 726–37PubMedCrossRefGoogle Scholar
  196. 196.
    Stratta RJ, Alloway RR, Hodge E, et al. A multicenter, open-label, comparative trial of two daclizumab dosing strategies vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids for the prevention of acute rejection in simultaneous kidney-pancreas transplant recipients: interim analysis. Clin Transplant 2002 Feb; 16(1): 60–8Google Scholar
  197. 197.
    Burke III GW, Kaufman DB, Bruce DS, et al. The effect of antibody induction in simultaneous pancreas kidney (SPK) transplant patients receiving tacrolimus (TAC) and mycophenolate mofetil (MMF): two-year results [abstract no. 14]. Am J Transplant 2002; 2 Suppl. 3: 141Google Scholar
  198. 198.
    Jordan ML, Chakrabarti P, Luke P, et al. Results of pancreas transplantation after steroid withdrawal under tacrolimus immunosuppression. Transplantation 2000 Jan 27; 69(2): 265–71PubMedCrossRefGoogle Scholar
  199. 199.
    Steurer W, Tabbi MG, Oellinger R, et al. Steroid withdrawal after simultaneous pancreas-kidney transplantation is safe under tacrolimus/MMF immunosuppression. Transplantation 2002 Aug 27; 74 Suppl.: 569–70Google Scholar
  200. 200.
    Kaufman DB, Leventhal JR, Koffron AJ, et al. A prospective study of rapid corticosteroid elimination in simultaneous pancreas-kidney transplantation: comparison of two maintenance immunosuppression protocols: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus. Transplantation 2002 Jan 27; 73(2): 169–77PubMedCrossRefGoogle Scholar
  201. 201.
    Black R. Islet cell transplantation in type 1 diabetes —trials show promise. Inpharma 2001 May 12; 1287: 3–4Google Scholar
  202. 202.
    Shapiro AM, Lakey JRT, Ryan EA, et al. Islet transplantation in seven patients with type I diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230–8PubMedCrossRefGoogle Scholar
  203. 203.
    Hiraoka A, Ohashi Y, Okamoto S, et al. Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation. Bone Marrow Transplant 2001 Jul; 28(2): 181–5PubMedCrossRefGoogle Scholar
  204. 204.
    Nash RA, Antin JH, Karanes C, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 2000 Sep 15; 96(6): 2062–8PubMedGoogle Scholar
  205. 205.
    Yanik G, Levine JE, Ratanatharathorn V, et al. Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation. Bone Marrow Transplant 2000 Jul; 26(2): 161–7PubMedCrossRefGoogle Scholar
  206. 206.
    Furlong T, Storb R, Anasetti C, et al. Clinical outcome after conversion to FK 506 (tacrolimus) therapy for acute graft-versus-host disease resistant to cyclosporine or for cyclosporine-associated toxicities. Bone Marrow Transplant 2000 Nov; 26(9): 985–91PubMedCrossRefGoogle Scholar
  207. 207.
    Durrant S, Mollee P, Morton AJ, et al. Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis. Br J Haematol 2001; 113: 217–23PubMedCrossRefGoogle Scholar
  208. 208.
    Baran DA, Galin ID, Sandier D, et al. Predictors of early renal insufficiency in cardiac transplant recipients initiated on tacrolimus. Transplant Proc 2002; 34(5): 1872–3PubMedCrossRefGoogle Scholar
  209. 209.
    Shimizu T, Tanabe K, Tokumoto T, et al. Clinical and histological analysis of acute tacrolimus (TAC) nephrotoxicity in renal allografts. Clin Transplant 1999; 13 Suppl. 1: 48–53PubMedGoogle Scholar
  210. 210.
    Wondimu B, Németh A, Modeer T. Oral health in liver transplant children administered cyclosporin A or tacrolimus. Int J Paediatr Dent 2001 Nov; 11(6): 424–9PubMedCrossRefGoogle Scholar
  211. 211.
    Thorp M, DeMattos A, Bennett W, et al. The effect of conversion from cyclosporine to tacrolimus on gingival hyperplasia, hirsutism and cholesterol. Transplantation 2000 Mar 27; 69(6): 1218–20PubMedCrossRefGoogle Scholar
  212. 212.
    James JA, Jamal S, Hull PS, et al. Tacrolimus is not associated with gingival overgrowth in renal transplant patients. J Clin Periodontol 2001 Sep; 28(9): 848–52PubMedCrossRefGoogle Scholar
  213. 213.
    James JA, Boomer S, Maxwell AP, et al. Reduction in gingival overgrowth associated with conversion from cyclosporin A to tacrolimus. J Clin Periodontol 2000 Feb; 27(2): 144–8PubMedCrossRefGoogle Scholar
  214. 214.
    Vallejo C, Iniesta P, Moraleda JM. Resolution of cyclosporine-induced gingival hyperplasia resistant to azithromycin by switching to tacrolimus. Haematologica 2001; 86(1): 110PubMedGoogle Scholar
  215. 215.
    Marchetti P, Navalesi R. The metabolic effects of cyclosporin and tacrolimus. J Endocrinol Invest 2000; 23(7): 482–90PubMedGoogle Scholar
  216. 216.
    Markell MS. Post-transplant diabetes: incidence, relationship to choice of immunosuppressive drugs, and treatment protocol. Adv Ren Replace Ther 2001 Jan; 8(1): 64–9PubMedCrossRefGoogle Scholar
  217. 217.
    Montori VM, Basu A, Erwin PJ, et al. Posttransplantation diabetes: a systematic review of the literature. Diabetes Care 2002 Mar; 25(3): 583–92PubMedCrossRefGoogle Scholar
  218. 218.
    Hricik DE, Anton HAS, Knauss TC, et al. Outcomes of African American kidney transplant recipients treated with sirolimus, tacrolimus, and corticosteroids. Transplantation 2002 Jul 27; 74(2): 189–93PubMedCrossRefGoogle Scholar
  219. 219.
    Al-Uzri A, Stablein DM, A Cohn R. Posttransplant diabetes mellitus in pediatric renal transplant recipients: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation 2001 Sep 27; 72(6): 1020–4PubMedCrossRefGoogle Scholar
  220. 220.
    Maes BD, Kuypers D, Messiaen T, et al. Posttransplantation diabetes mellitus in FK-506-treated renal transplant recipients: analysis of incidence and risk factors. Transplantation 2001 Nov 27; 72(10): 1655–61PubMedCrossRefGoogle Scholar
  221. 221.
    Bloom RD, Rao V, Weng F, et al. Association of hepatitis C with posttransplant diabetes in renal transplant patients on tacrolimus. J Am Soc Nephrol 2002 May; 13(5): 1374–80PubMedCrossRefGoogle Scholar
  222. 222.
    Baid S, Tolkoff-Rubin N, Farrell ML, et al. Tacrolimus-associated posttransplant diabetes mellitus in renal transplant recipients: role of hepatitis C infection. Transplant Proc 2002; 34(5): 1771–3PubMedCrossRefGoogle Scholar
  223. 223.
    Kasiske BL, Snyder JJ, Gilbertson D, et al. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 2003 Feb; 3(2): 178–85PubMedCrossRefGoogle Scholar
  224. 224.
    Coley KC, Verrico MM, McNamara DM, et al. Lack of tacrolimus-induced cardiomyopathy. Ann Pharmacother 2001 Sep; 35(9): 985–9PubMedCrossRefGoogle Scholar
  225. 225.
    Espino G, Denney J, Furlong T, et al. Assessment of myocardial hypertrophy by echocardiography in adult patients receiving tacrolimus or cyclosporine therapy for prevention of acute GVHD. Bone Marrow Transplant 2001 Dec; 28(12): 1097–103PubMedCrossRefGoogle Scholar
  226. 226.
    Nakata Y, Yoshibayashi M, Yonemura T, et al. Tacrolimus and myocardial hypertrophy. Transplantation 2000; 69(9): 1960–2PubMedCrossRefGoogle Scholar
  227. 227.
    Dharnidharka VR, Sullivan EK, Stablein DM, et al. Risk factors for posttransplant lymphoproliferative disorder (PTLD) in pediatric kidney transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation 2001 Apr 27; 71(8): 1065–8PubMedCrossRefGoogle Scholar
  228. 228.
    Younes BS, McDiarmid SV, Martin MG, et al. The effect of immunosuppression on posttransplant lymphoproliferative disease in pediatric liver transplant patients. Transplantation 2000 Jul 15; 70(1): 94–9PubMedGoogle Scholar
  229. 229.
    Dharnidharka VR, Ho P-L, Stablein DM, et al. Mycophenolate, tacrolimus and post-transplant lymphoproliferative disorder: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant 2002 Oct; 6(5): 396–9PubMedCrossRefGoogle Scholar
  230. 230.
    Jain A, Nalesnik M, Reyes J, et al. Posttransplant lymphoproliferative disorders in liver transplantation: a 20-year experience. Ann Surg 2002 Oct; 236(4): 429–36; discussion 436-7PubMedCrossRefGoogle Scholar
  231. 231.
    Cacciarelli TV, Reyes J, Jaffe R, et al. Primary tacrolimus (FK506) therapy and the long-term risk of post-transplant lymphoproliferative disease in pediatric liver transplant recipients. Pediatr Transplant 2001 Oct; 5(5): 359–64PubMedCrossRefGoogle Scholar
  232. 232.
    Jain A, Mazariegos G, Kashyap R, et al. Pediatric liver transplantation: a single center experience spanning 20 years. Transplantation 2002 Mar 27; 73(6): 941–7PubMedCrossRefGoogle Scholar
  233. 233.
    Armenti VT, Coscia LA, McGrory CH, et al. National Transplantation Pregnancy Registry looks at outcomes with Neoral and Tacrolimus. Nephrol News Issues 2000 Aug; 14(9): S11PubMedGoogle Scholar
  234. 234.
    Kainz A, Harabacz I, Cowlrick IS, et al. Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus. Transplantation 2000 Dec 27; 70(12): 1718–21PubMedCrossRefGoogle Scholar
  235. 235.
    Jurewicz WA, Kumar N, McKenna M, et al. Pharmaco-economic analysis of tacrolimus and cyclosporin microemulsion in kidney transplantation [abstract]. 2nd International Congress on Immunosuppression; 2001 Dec 6–8; San Diego (CA), 144Google Scholar
  236. 236.
    Craig A, McKechnie T, McKenna M, et al. A cost-effectiveness analysis of tacrolimus versus cyclosporine microemulsion following kidney transplantation. Transplant Proc 2002 Aug; 34(5): 1646–8PubMedCrossRefGoogle Scholar
  237. 237.
    Lazzaro C, McKechnie T, McKenna M, et al. Tacrolimus versus cyclosporin in renal transplantation in Italy: cost minimisation and cost-effectiveness analyses. J Nephrol 2002; 15: 580–8PubMedGoogle Scholar
  238. 238.
    Rabkin JM, Corless CL, Rosen HR, et al. Pharmacoeconomic study of tacrolimus-based versus cyclosporine-based immunosuppressive therapy following liver transplantation. Transplant Proc 2001; 33(1–2): 1532–4PubMedCrossRefGoogle Scholar
  239. 239.
    Black R. Tacrolimus worth the extra cost in kidney transplantation. Pharmacoecon Outcomes News 2001; 310: 3–4Google Scholar
  240. 240.
    Fujisawa Healthcare Inc.. Tacrolimus comments. Osaka: Fujisawa Healthcare Inc, 2003 Apr 17 [data on file]Google Scholar
  241. 241.
    Taylor DO, Barr ML, Meiser BM, et al. Suggested guidelines for the use of tacrolimus in cardiac transplant recipients. J Heart Lung Transplant 2001 Jul; 20(7): 734–8PubMedCrossRefGoogle Scholar
  242. 242.
    Garrity ER, Hertz MI, Trulock EP, et al. Suggested guidelines for the use of tacrolimus in lung-transplant recipients. J Heart Lung Transplant 1999; 18(3): 175–6PubMedCrossRefGoogle Scholar
  243. 243.
    Gruessner RWG, Bartlett ST, Burke GW, et al. Suggested guidelines for the use of tacrolimus in pancreas/kidney transplantation. Clin Transplantation 1998; 12: 260–6Google Scholar
  244. 244.
    Meier-Kriesche H-U, Ojo AO, Hanson JA, et al. Increased impact of acute rejection on chronic allograft failure in recent era. Transplantation 2000 Oct 15; 70(7): 1098–100PubMedCrossRefGoogle Scholar
  245. 245.
    Jacobsohn DA, Vogelsang GB. Novel pharmacotherapeutic approaches to prevention and treatment of GVHD. Drugs 2002; 62(6): 879–89PubMedCrossRefGoogle Scholar
  246. 246.
    Denton MD, Magee CC, Sayegh MH. Immunosuppressive strategies in transplantation. Lancet 1999; 353: 1083–91PubMedCrossRefGoogle Scholar
  247. 247.
    Boucek Jr RJ, Boucek MM. Pediatric heart transplantation. Curr Opin Pediatr 2002 Oct; 14(5): 611–9PubMedCrossRefGoogle Scholar
  248. 248.
    van Mourik ID, Kelly DA. Immunosuppressive drugs in paediatric liver transplantation. Paediatr Drugs 2001; 3(1): 43–60PubMedCrossRefGoogle Scholar
  249. 249.
    Veenendaal RA, Ringers J, Baranski A, et al. Clinical aspects of small-bowel transplantation. Scand J Gastroenterol 2000; 232 Suppl.: 65–8Google Scholar
  250. 250.
    Cohen SM. Current immunosuppression in liver transplantation. Am J Ther 2002 Mar-2002 30; 9(2): 119–25PubMedCrossRefGoogle Scholar
  251. 251.
    Debray D, Furlan V, Baudouin V, et al. Therapy for acute rejection in pediatric organ transplant recipients. Paediatr Drugs 2003; 5(2): 81–93PubMedGoogle Scholar
  252. 252.
    del Mar Fernández de Gatta M, Santos-Buelga D, Domínguez-Gil A, et al. Immunosuppressive therapy for paediatric transplant patients: pharmacokinetic considerations. Clin Pharmacokinet 2002; 41(2): 115–35PubMedCrossRefGoogle Scholar
  253. 253.
    Zecca M, Locatelli F. Management of graft-versus-host disease in paediatric bone marrow transplant recipients. Paediatr Drugs 2000 Jan-2000 28; 2(1): 29–55PubMedGoogle Scholar
  254. 254.
    Mazariegos GV, Salzedas AA, Zavatsky J, et al. Long term management of liver transplant rejection in children. Biodrugs 2000 Jul; 14: 31–48PubMedCrossRefGoogle Scholar
  255. 255.
    Shapiro R. The development of tacrolimus in renal transplantation. Transplant Proc 2001 Nov-2001 31; 33(7–8): 3158–60PubMedCrossRefGoogle Scholar
  256. 256.
    Berloco P, Rossi M, Pretagostini R, et al. Tacrolimus as cornerstone immunosuppressant in kidney transplantation. Transplant Proc 2001 Feb-2001 31; 33(1–2): 994–6PubMedCrossRefGoogle Scholar
  257. 257.
    First MR. Strategies to minimize immunological and nonimmunological risk factors in the renal transplant population. Transplantation 2001 Sep 27; 72(6 Suppl.): S20–4PubMedCrossRefGoogle Scholar
  258. 258.
    Kreis H, Cisterne J-M, Land W, et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 2000; 69(7): 1252–60PubMedCrossRefGoogle Scholar
  259. 259.
    Gregoor S, de Sevaux RGL, Ligtenberg G, et al. A prospective, randomised study of withdrawal of cyclosporine or prednisone in renal transplant recipients treated with mycophenolate mofetil, cyclosporine, and prednisone: 18 months follow-up data [abstract no. 441]. Am J Transplant 2001; 1 Suppl. 1: 246Google Scholar
  260. 260.
    Vincenti F, Ramos E, Brattstrom C, et al. Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation. Transplantation 2001; 71(9): 1282–7PubMedCrossRefGoogle Scholar
  261. 261.
    Kahan BD, Keown P, Levy GA, et al. Therapeutic drug monitoring of immunosuppressant drugs in clinical practice. Clin Ther 2002 Mar; 24(3): 330–50; discussion 329PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Lesley J. Scott
    • 1
    Email author
  • Kate McKeage
    • 1
  • Susan J. Keam
    • 1
  • Greg L Plosker
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

Personalised recommendations