Selected Immunosuppressants/Selected Azole Antifungal Agents Interactions

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Antifungal medicines may may slow down how quickly your body processes cyclosporine, sirolimus, tacrolimus, and temsirolimus.

What might happen:

Your blood levels of cyclosporine, sirolimus, tacrolimus, or temsirolimus may increase and cause toxic effects that may harm your kidneys.

What you should do about this interaction:

Make sure that your doctor knows all of the medicines that you are taking.Tell your doctor if you have any kidney problems. If you experience any shortness of breath, unusual swelling, changes in the color or amount of your urine, or changes in how often you urinate, contact your doctor.The amount of cyclosporine, sirolimus, tacrolimus, or temsirolimus in your blood may need to be checked more often and the dosage adjusted when you first start or stop taking the antifungal medicine.Your healthcare professionals (e.g. doctor or pharmacist) may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

  • 1.Ferguson RM, Sutherland DE, Simmons RL, Najarian JS. Ketoconazole, cyclosporin metabolism, and renal transplantation. Lancet 1982 Oct 16; 2(8303):882-3.
  • 2.Daneshmend TK. Ketoconazole-cyclosporin interaction. Lancet 1982 Dec 11; 2(8311):1342-3.
  • 3.Smith JM, Hows JM, Gordon-Smith EC, Baughan A, Goldman JM. Interaction of CyA and ketoconazole. Clin Sci 1983;64(2):67P.
  • 4.Shepard JH, Canafax DM, Simmons RL, Najarian JS. Cyclosporine-ketoconazole: a potentially dangerous drug-drug interaction. Clin Pharm 1986 Jun;5(6):468.
  • 5.Kwan JT, Foxall PJ, Davidson DG, Bending MR, Eisinger AJ. Interaction of cyclosporin and itraconazole. Lancet 1987 Aug 1;2(8553):282.
  • 6.Novakova I, Donnelly P, de Witte T, de Pauw B, Boezeman J, Veltman G. Itraconazole and cyclosporin nephrotoxicity. Lancet 1987 Oct 17; 2(8564):920-1.
  • 7.Trenk D, Brett W, Jahnchen E, Birnbaum D. Time course of cyclosporin/itraconazole interaction. Lancet 1987 Dec 5;2(8571):1335-6.
  • 8.Daneshmend TK, Warnock DW. Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinet 1988 Jan;14(1):13-34.
  • 9.Sugar AM, Saunders C, Idelson BA, Bernard DB. Interaction of fluconazole and cyclosporine. Ann Intern Med 1989 May 15;110(10):844.
  • 10.Collignon P, Hurley B, Mitchell D. Interaction of fluconazole with cyclosporin. Lancet 1989 Jun 3;1(8649):1262.
  • 11.Charles BG, Ravenscroft PJ, Rigby RJ. The ketoconazole-cyclosporin interaction in an elderly renal transplant patient. Aust N Z J Med 1989 Jun;19(3):292-3.
  • 12.Baciewicz AM, Baciewicz FA Jr. Cyclosporine pharmacokinetic drug interactions. Am J Surg 1989 Feb;157(2):264-71.
  • 13.First MR, Schroeder TJ, Weiskittel P, Myre SA, Alexander JW, Pesce AJ. Concomitant administration of cyclosporin and ketoconazole in renal transplant recipients. Lancet 1989 Nov 18;2(8673):1198-201.
  • 14.Frey FJ. Concomitant cyclosporin and ketoconazole. Lancet 1990 Jan 13; 335(8681):109-10.
  • 15.Ah-Sing E, Poole TW, Ioannides C, King LJ. Mechanism of the ketoconazole-cyclosporin interaction. Arch Toxicol 1990;64(6):511-3.
  • 16.Lazar JD, Wilner KD. Drug interactions with fluconazole. Rev Infect Dis 1990 Mar-Apr;12 Suppl 3:S327-33.
  • 17.Katzir D, Balschke TF. The cyclosporine-ketoconazole interaction. Hosp Ther 1990 Jan;15:99-112.
  • 18.First MR, Schroeder TJ, Alexander JW, Stephens GW, Weiskittel P, Myre SA, Pesce AJ. Cyclosporine dose reduction by ketoconazole administration in renal transplant recipients. Transplantation 1991 Feb;51(2):365-70.
  • 19.Canafax DM, Graves NM, Hilligoss DM, Carleton BC, Gardner MJ, Matas AJ. Increased cyclosporine levels as a result of simultaneous fluconazole and cyclosporine therapy in renal transplant recipients: a double- blind, randomized pharmacokinetic and safety study. Transplant Proc 1991 Feb; 23(1 Pt 2):1041-2.
  • 20.Albengres E, Tillement JP. Cyclosporin and ketoconazole, drug interaction or therapeutic association?. Int J Clin Pharmacol Ther Toxicol 1992 Dec; 30(12):555-70.
  • 21.Lopez-Gil JA. Fluconazole-cyclosporine interaction: a dose-dependent effect?. Ann Pharmacother 1993 Apr;27(4):427-30.
  • 22.First MR, Schroeder TJ, Michael A, Hariharan S, Weiskittel P, Alexander JW. Cyclosporine-ketoconazole interaction. Long-term follow-up and preliminary results of a randomized trial. Transplantation 1993 May; 55(5):1000-4.
  • 23.Rapamune (sirolimus) US prescribing information. Wyeth Pharmaceuticals July, 2019.
  • 24.Sadaba B, Campanero MA, Quetglas EG, Azanza JR. Clinical relevance of sirolimus drug interactions in transplant patients. Transplant Proc 2004 Dec;36(10):3226-8.
  • 25.Said A, Garnick JJ, Dieterle N, Peres E, Abidi MH, Ibrahim RB. Sirolimus-itraconazole interaction in a hematopoietic stem cell transplant recipient. Pharmacotherapy 2006 Feb;26(2):289-95.
  • 26.Thomas PP, Manivannan J, John GT, Jacob CK. Sirolimus and ketoconazole co-prescription in renal transplant recipients. Transplantation 2004 Feb 15;77(3):474-5.
  • 27.Torisel (temsirolimus) US prescribing information. Wyeth Pharmaceuticals, Inc. March, 2018.
  • 28.Manez R, Martin M, Raman D, Silverman D, Jain A, Warty V, Gonzalez-Pinto I, Kusne S, Starzl TE. Fluconazole therapy in transplant recipients receiving FK506. Transplantation 1994 May 27;57(10):1521-3.
  • 29.Osowski CL, Dix SP, Lin LS, Mullins RE, Geller RB, Wingard JR. Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients. Transplantation 1996 Apr 27;61(8):1268-72.
  • 30.Capone D, Gentile A, Imperatore P, Palmiero G, Basile V. Effects of itraconazole on tacrolimus blood concentrations in a renal transplant recipient. Ann Pharmacother 1999 Oct;33(10):1124-5.
  • 31.Billaud EM, Guillemain R, Tacco F, Chevalier P. Evidence for a pharmacokinetic interaction between itraconazole and tacrolimus in organ transplant patients. Br J Clin Pharmacol 1998 Sep;46(3):271-2.
  • 32.Furlan V, Parquin F, Penaud JF, Cerrina J, Ladurie FL, Dartevelle P, Taburet AM. Interaction between tacrolimus and itraconazole in a heart-lung transplant recipient. Transplant Proc 1998 Feb;30(1):187-8.
  • 33.Kramer MR, Merin G, Rudis E, Bar I, Nesher T, Bublil M, Milgalter E. Dose adjustment and cost of itraconazole prophylaxis in lung transplant recipients receiving cyclosporine and tacrolimus (FK 506). Transplant Proc 1997 Sep;29(6):2657-9.
  • 34.Katari SR, Magnone M, Shapiro R, Jordan M, Scantlebury V, Vivas C, Gritsch A, McCauley J, Starzl T, Demetris AJ, Randhawa PS. Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in kidney transplant recipients. Clin Transplant 1997 Jun;11(3):237-42.
  • 35.Floren LC, Bekersky I, Benet LZ, Mekki Q, Dressler D, Lee JW, Roberts JP, Hebert MF. Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. Clin Pharmacol Ther 1997 Jul;62(1):41-9.
  • 36.Prograf (tacrolimus) US prescribing information. Fujisawa Healthcare, Inc. June, 2019.
  • 37.Assan R, Fredj G, Larger E, Feutren G, Bismuth H. FK 506/fluconazole interaction enhances FK 506 nephrotoxicity. Diabete Metab 1994 Jan-Feb; 20(1):49-52.
  • 38.Mieles L, Venkataramanan R, Yokoyama I, Warty VJ, Starzl TE. Interaction between FK506 and clotrimazole in a liver transplant recipient. Transplantation 1991 Dec;52(6):1086-7.
  • 39.Cresemba (isavuconazonium sulfate) US prescribing information. Astellas Pharma US, Inc. December, 2019.
  • 40.Viesselmann CW, Descourouez JL, Jorgenson MR, Radke NA, Odorico JS. Clinically Significant Drug Interaction Between Clotrimazole and Tacrolimus in Pancreas Transplant Recipients and Associated Risk of Allograft Rejection. Pharmacotherapy 2016 Mar;36(3):335-41.
  • 41.Sporanox (itraconazole) US prescribing information. Janssen Pharmaceutica Products, L.P. May, 2018.
  • 42.Sparkes T, Lemonovich TL. Interactions between anti-infective agents and immunosuppressants-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019 Feb 28;e13510.
  • 43.He J, Yu Y, Yin C, Liu H, Zou H, Ma J, Yang W, Liu Y, Zhong L, Chen X. Clinically significant drug-drug interaction between tacrolimus and fluconazole in stable renal transplant recipient and literature review. J Clin Pharm Ther 2020 Apr;45(2):264-269.

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.