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Drug Safety

Erschienen in:

01.08.2002 | Review Article

Drug Interactions with Tacrolimus

verfasst von: Dr Teun van Gelder

Erschienen in: Drug Safety | Ausgabe 10/2002

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Abstract

Tacrolimus is a drug for which therapeutic drug monitoring is recommended. The existence of a wide variety of potential drug interactions further supports the current strategy of measuring whole blood tacrolimus concentrations in transplanted patients.

Cytochrome P450 (CYP)3A, the major phase I metabolising enzyme in humans, and the multi-drug efflux pump, P-glycoprotein, are present at high levels in the villus tip of enterocytes in the gastrointestinal tract. Oral bioavailability of tacrolimus can be increased by concomitant administration of inhibitors of either CYP3A or P-glycoprotein. CYP activity in the liver also influences tacrolimus concentrations. As a result, several drugs that are frequently being used in transplantation, such as corticosteroids and antifungal agents, will affect tacrolimus concentrations. Knowledge of such drug interactions is extremely important, as they may lead to clinically important under- or overexposure to tacrolimus, with acute rejection episodes or serious toxicity as a result.

Winkler M, Christians U. A risk-benefit assessment of tacrolimus in transplantation. Drug Saf 1995; 12: 348–57PubMedCrossRef

Jusko WJ, Thomson AW, Fung J, et al. Consensus document: therapeutic monitoring of tacrolimus (FK506). Ther Drug Monit 1995; 17: 606–14PubMedCrossRef

Krahenbuhl S, Menafoglio A, Giostra E, et al. Serious interaction between mibefadril and tacrolimus. Transplantation 1998; 66: 1113–5PubMedCrossRef

Chenhsu RY, Loong CC, Chou MH, et al. Renal allograft dysfunction associated with rifampicin-tacrolimus interaction. Ann Pharmacotherapy 2000; 34: 27–31CrossRef

Moreno M, Latorre A, Manzanares C, et al. Clinical management of tacrolimus drug interactions in renal transplant patients. Transpl Proc 1999; 31: 2252–3CrossRef

Brazelton TR, Morris RE. Molecular mechanisms of action of newxenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol 1996; 8: 710–20PubMedCrossRef

Kung L, Gourishankar S, Halloran PF. Molecular pharmacology of immunosuppressive agents in relation to their clinical use. Curr Opin Organ Transplant 2000; 5: 268–75CrossRef

Spencer CM, Goa KL, Gillis JC. Tacrolimus: an update of its pharmacology and clinical efficacy in the management of organ transplantation. Drugs 1997; 54: 925–75PubMedCrossRef

Sewing KF. Pharmacokinetics, dosing principles, and blood level monitoring of FK506. Transplant Proc 1994; 26: 3267–9PubMed

10.

Venkataramanan R, Swaminathan A, Prasad T, et al. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinetic 1995; 29: 404–30CrossRef

11.

Bekersky I, Dressler 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: 176–82PubMedCrossRef

12.

Christiaans M, van Duijnhoven E, Beysens T, et al. Effect of breakfast on the oral bioavailability of tacrolimus and changes in pharmacokinetics at different times post-transplant in renal transplant recipients. Transplant Proc 1998; 30: 1271–3PubMedCrossRef

13.

Bekersky I, Dressler D, Alak A, et al. Comparative tacrolimus pharmacokinetics: normal versusmildly hepatically impaired subjects. J Clin Pharmacol 2001; 41: 628–35PubMedCrossRef

14.

Wallemacq PE, Verbeeck RK. Comparative clinical pharmacokinetics of tacrolimus in paediatric and adult patients. Clin Pharmacokinet 2001; 40: 283–95PubMedCrossRef

15.

Garcia Sanchez MJ, Manzanares C, Santos-Buelga D, et al. Covariate effects on the apparent clearance of tacrolimus in paediatric liver transplant patients undergoing conversion therapy. Clin Pharmacokinetic 2001; 40: 63–71CrossRef

16.

Sheiner PA, Mor E, Chodoff L, et al. Acute renal failure associated with the use of ibuprofen in two liver transplant recipients on FK506. Transplantation 1993; 57: 1132–3

17.

Lake KD, Canafax DM. Important interactions of drugs with immunosuppressive agents used in transplant recipients. J Antimicrob Chemother 1995; 36Suppl. B: 11–22PubMedCrossRef

18.

Bekersky I, Dressler D, Mekki Q. Effect of time of meal consumption on bioavailability of a single oral 5 mg tacrolimus dose. J Clin Pharmacol 2001; 41: 289–97PubMedCrossRef

19.

Fleckenstein JF, Paredes M, Thuluvath PJ. A prospective, randomized, double-blind trial evaluating the efficacy of ursodeoxicholic acid in prevention of liver transplant rejection. Liver Transpl Surg 1998; 4: 276–9PubMedCrossRef

20.

Zhang Y, Benet LZ. The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and p-glycoprotein. Clin Pharmacokinet 2001; 40: 159–68PubMedCrossRef

21.

Fricker G, Miller DS. Relevance of multidrug resistance proteins for intestinal drug absorption in vitro and in vivo. Pharmacol Toxicol 2002; 90: 5–13PubMedCrossRef

22.

Von Ahsen N, Richter M, Grupp C, et al. No influence of the MDR-1 C3435T polymorphismor a CYP3A4 promotor polymorphisms (CYP3A4-V allele) on dose-adjusted cyclosporine A trough concentrations or rejection incidence in stable renal transplant recipients. Clin Chem 2001; 47: 1048–52

23.

Piekoszewski W, Jusko WJ. Plasma protein binding of tacrolimus in humans. J Pharm Sci 1993; 82: 340–1PubMedCrossRef

24.

Nagase K, Iwasaki K, Nozaki K, et al. Distribution and protein binding of FK506, a potent immunosuppressive macrolide lactone, in human blood and its uptake by erythrocytes. J Pharm Pharmacol 1994; 46: 113–7PubMedCrossRef

25.

Iwasaki K, Shiraga T, Matsuda H, et al. Further metabolism of FK506 (tacrolimus). Identification and biological activities of the metabolites oxidized at multiple sites of FK506. Drug Metab Dispos 1995; 23: 28–34PubMed

26.

Alak AM, Moy S. Biological activity of tacrolimus (FK506) and its main metabolites from whole blood of kidney transplant recipients. Transplant Proc 1997; 29: 2487–90PubMedCrossRef

27.

Christians U, Schmidt G, Guengerich FP, et al. In vitro metabolism of FK506, cytochrome P450 and drug interactions. Ther Drug Monit 1993; 15: 145CrossRef

28.

Christians U, Schmidt G, Bader A, et al. Identification of drugs inhibiting the in vitro metabolism of tacrolimus by human liver microsomes. Br J Clin Pharmacol 1996; 41: 187–90PubMedCrossRef

29.

Hebert MF, Fisher RM, Marsh CL, et al. Effects of rifampicin on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 1999; 39: 91–6PubMedCrossRef

30.

Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John’s wort. Lancet 2000; 355: 548–9PubMedCrossRef

31.

Smak Gregoor PJH, van Gelder T, van der Ende ME, et al. Cyclosporine and triple-drug treatment with human immunodeficiency virus protease inhibitors. Transplantation 1999; 68: 1210–1CrossRef

32.

Sheikh AM, Wolf DC, Lebovics E, et al. Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels. Transplantation 1999; 68: 307–9PubMedCrossRef

33.

Schwrcz R, Rudbeck G, Soderdahl G, et al. Interaction between nelfinavir and tacrolimus after orthotopic liver transplantation in a patient coinfected with HIV and hepatitis C virus (HCV). Transplantation 2000; 69: 2194–5CrossRef

34.

Keay S, Oldach D, Redfield R, et al. Organ transplantation in the HIV-infected patient. Curr Opin Organ Transpl 2000; 5: 217–23CrossRef

35.

Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6′,7′-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and p-glycoprotein. Clin Pharmacol Ther 1999; 65: 237–44PubMedCrossRef

36.

Kane GC, Lipsky JJ. Drug-grapefruit juice interactions. Mayo Clin Proc 2000; 75: 933–42PubMedCrossRef

37.

Michelangelo V, Piero D, Elisa C, et al. Grapefruit juice and kinetics of tacrolimus [abstract]. J Am Soc Nephrol 2001; 12: 862A

38.

Undre NA, Schafer A, and the European Tacrolimus Multicentre Renal Study Group. Factors affecting the pharmacokinetics of tacrolimus in the first year after renal transplantation. Transplant Proc 1998; 30: 1261–3PubMedCrossRef

39.

Albengres E, LeLouet H, Tillement JP. Systemic antifungal agents: drug interactions of clinical significance. Drug Saf 1998; 18(2): 83–97PubMedCrossRef

40.

Mignat C. Clinically significant drug interactions with new immunosuppressive drugs. Drug Saf 1997; 16(4): 267–78PubMedCrossRef

41.

Zucker K, Rosen A, Tsaroucha A, et al. Unexpected augmentation of mycophenolic acid pharmacokinetics in renal transplant patients receiving tacrolimus and mycophenolate mofetil in combination therapy, and analogous in vitro findings. Transpl Immunol 1997; 5: 225–32PubMedCrossRef

42.

Smak Gregoor PJH, Van Gelder T, Hesse CJ, et al. Mycophenolic acid plasma concentrations in kidney allograft recipients with or without cyclosporin: a cross-sectional study. Nephrol Dial Transplant 1999; 14(3): 706–8PubMedCrossRef

43.

Smak Gregoor PJH, De Sévaux RGL, Henè RJ, et al. Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients. Transplantation 1999; 68(10): 1603–6CrossRef

44.

Van Gelder T, Klupp J, Barten MJ, et al. Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid. Ther Drug Monit 2001; 23: 119–28PubMedCrossRef

45.

Filler G, Zimmering M, Mai I. Pharmacokinetics of mycophenolate mofetil are influenced by concomitant immunosuppression. Pediatr Nephrol 2000; 14: 100–4PubMedCrossRef

46.

Pirsch J, Bekersky I, Vincenti F, et al. Coadministration of tacrolimus and mycophenolate mofetil in stable kidney transplant patients: pharmacokinetics and tolerability. J Clin Pharm 2000; 40: 527–32CrossRef

47.

Christians U, Jacobsen W, Floren LC. Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients: are the statins mechanistically similar? Pharmacol Ther 1998; 80: 1–34PubMedCrossRef

48.

Mück W, Neal DAJ, Boix O, et al. Tacrolimus/cerivastatin interaction study in liver transplant recipients. Brit J Clin Pharmacol 2001; 52: 213–7CrossRef

49.

Penson MG, Fricker FJ, Thompson JR, et al. Safety and efficacy of pravastatin therapy for the prevention of hyperlipidemia in pediatric and adolescent cardiac transplant recipients. J Heart Lung Transplant 2001; 20: 611–8PubMedCrossRef

50.

Manzanares C, Moreno M, Castellanos F, et al. Influence of hepatitis C virus infection on FK506 blood levels in renal transplant patients. Transplant Proc 1998; 30: 1264–5PubMedCrossRef

51.

Armstrong V, Oellerich M. New developments in the immunosuppressive drug monitoring of cyclosporine, tacrolimus and azathioprine. Clin Biochem 2001; 34: 9–16PubMedCrossRef

Titel: Drug Interactions with Tacrolimus
verfasst von: Dr Teun van Gelder
Publikationsdatum: 01.08.2002
Verlag: Springer International Publishing
Erschienen in: Drug Safety / Ausgabe 10/2002
Print ISSN: 0114-5916
Elektronische ISSN: 1179-1942
DOI: https://doi.org/10.2165/00002018-200225100-00003

Springer Medizin

Abstract

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