Basic Information
ID DDInter458 and DDInter1722
Interaction Sulfonamides may significantly reduce serum cyclosporine concentrations by an unknown mechanism. Allograft rejections have resulted. Hyperkalemia and additive nephrotoxicity has also been reported. The mechanism is unknown. Data are available for intravenous trimethoprim-sulfamethoxazole, intravenous sulfamethazine (no longer marketed), oral sulfadiazine, and sulfasalazine. Oral trimethoprim-sulfamethoxazole reportedly does not affect cyclosporine levels.
Management Renal function and cyclosporine levels should be closely monitored if these drugs must be used concomitantly.
References [1] Cockburn IT, Krupp P "An appraisal of drug interactions with sandimmun." Transplant Proc 21 (1989): 3845-50 [2] Ringden O, Myrenfors P, Klintmalm G, Tyden G, Ost L "Nephrotoxicity by co-trimoxazole and cyclosporin in transplanted patients." Lancet 1 (1984): 1016-7 [3] Berg K, Gjellestad A, Nordby G, et al "Renal effects of trimethoprim in ciclosporin- and azathioprine-treated kidney-allografted patients." Nephron 53 (1989): 218-22 [4] Yee GC, McGuire TR "Pharmacokinetic drug interactions with cyclosporin (Part I)." Clin Pharmacokinet 19 (1990): 319-32 [5] Wallwork J, McGregor CG, Wells FC, Cory-Pearace R, English TA "Cyclosporin and intravenous sulphadimidine and trimethoprim therapy." Lancet 1 (1983): 326-7 [6] Spes CH, Angermann CE, Stempfle HU, et al "Sulfadiazine therapy for toxoplasmosis in heart transplant recipients decreases cyclosporine concentration." Clin Investig 70 (1992): 752-4 [7] Wallwork J, McGregor CG, Wells FC, et al "Cyclosporin and intravenous sulphadimidine and trimethoprim therapy." Lancet 02/12/83 (1983): 366-7 [8] DuCheyron D, Debruyne D, Lobbedez T, Richer C, Ryckelynck JP, deLigny BH "Effect of sulfasalazine on cyclosporin blood concentration." Eur J Clin Pharmacol 55 (1999): 227-8 [9] Jones DK, Hakim M, Wallwork J, Higenbottam TW "Serious interaction between cyclosporin A and sulphadimidine." Br Med J 292 (1986): 728-9 [10] Ducharme MP, Warbasse LH, Edwards DJ "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice." Clin Pharmacol Ther 57 (1995): 485-91 [11] Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF, Hunsicker LG "Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients." Transplantation 62 (1996): 123-5 [12] Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77 [13] Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8 [14] "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4 [15] Honcharik N, Yatscoff RW, Jeffery JR, Rush DN "The effect of meal composition on cyclosporine absorption." Transplantation 52 (1991): 1087-9 [16] Tsunoda SM, Harris RZ, Christians U, et al. "Red wine decreases cyclosporine bioavailability." Clin Pharmacol Ther 70 (2001): 462-7 [17] Yee GC, Stanley DL, Pessa LJ, et al. "Effect of grrapefruit juice on blood cyclosporin concentration." Lancet 345 (1995): 955-6 [18] Ioannidesdemos LL, Christophidis N, Ryan P, Angelis P, Liolios L, Mclean AJ "Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases." J Rheumatol 24 (1997): 49-54 [19] Oliveira-Freitas VL, Dalla Costa T, Manfro RC, Cruz LB, Schwartsmann G "Influence of purple grape juice in cyclosporine availability." J Ren Nutr 20 (2010): 309-13 [20] Tan KKC, Trull AK, Uttridge JA, Metcalfe S, Heyes CS, Facey S, Evans DB "Effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine in kidney transplant recipients." Clin Pharmacol Ther 57 (1995): 425-33 [21] Hollander AAMJ, Vanrooij J, Lentjes EGWM, Arbouw F, Vanbree JB, Schoemaker RC, Vanes LA, Vanderwoude FJ, Cohen AF "The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients." Clin Pharmacol Ther 57 (1995): 318-24 [22] Ducharme MP, Provenzano R, Dehoornesmith M, Edwards DJ "Trough concentrations of cyclosporine in blood following administration with grapefruit juice." Br J Clin Pharmacol 36 (1993): 457-9
Alternative for Cyclosporine L04A
Deucravacitinib Teprotumumab Azathioprine Antithymocyte immunoglobulin (rabbit) Tacrolimus Leflunomide
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Alternative for Sulfadoxine P01B
Proguanil Artesunate Mefloquine Pyrimethamine Tafenoquine Artemether
Lumefantrine Primaquine

G01A
Methazolamide Tioconazole Probenecid
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.