Cyclosporine (Oral) interactions

Food & lifestyle

• grapefruit juice

  Moderate

  Metabolism

  Administration with grapefruit juice (compared to water or orange juice) has been shown to increase blood concentrations of cyclosporine with a relatively high degree of interpatient variability. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

  What to do: Patients receiving cyclosporine therapy should be advised to either refrain from or avoid fluctuations in the consumption of grapefruits and grapefruit juice. Until more data are available, the consumption of red wine or purple grape juice should preferably be avoided or limited. All oral formulations of cyclosporine should be administered on a consistent schedule with regard to time of day and relation to meals so as to avoid large fluctuations in plasma drug levels.

  13 sources

  1. Honcharik N, Yatscoff RW, Jeffery JR, Rush DN "The effect of meal composition on cyclosporine absorption." Transplantation 52 (1991): 1087-9
  2. 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
  3. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  4. 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
  5. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  6. 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
  7. Yee GC, Stanley DL, Pessa LJ, et al. "Effect of grrapefruit juice on blood cyclosporin concentration." Lancet 345 (1995): 955-6
  8. Ducharme MP, Warbasse LH, Edwards DJ "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice." Clin Pharmacol Ther 57 (1995): 485-91

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  9. 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
  10. 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
  11. 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
  12. Tsunoda SM, Harris RZ, Christians U, et al. "Red wine decreases cyclosporine bioavailability." Clin Pharmacol Ther 70 (2001): 462-7
  13. 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

Conditions

Conditions in which Cyclosporine (Oral) needs care, as documented in this source.

• Hypertension

  Major

  The use of cyclosporine is contraindicated in patients with rheumatoid arthritis or psoriasis with uncontrolled hypertension. Hypertension, possibly due to renal vasoconstriction, has occurred in 50% of patients receiving cyclosporine. Antihypertensive therapy may be necessary for kidney, liver, and heart transplant recipients treated with cyclosporine. Hypertension may decline with continued used, but has persisted in some patients.

  3 sources

  1. "Product Information. SandIMMUNE (cycloSPORINE)." Apothecon Inc (2022):
  2. Textor SC, Canzanello VJ, Taler SJ, Wilson DJ, Schwartz LL, Augustine JE, Raymer JM, Romero JC, Wiesner RH, Krom RAF, B "Cyclosporine-induced hypertension after transplantation." Mayo Clin Proc 69 (1994): 1182-93
  3. "Product Information. Neoral (cycloSPORINE)." Sandoz Pharmaceuticals Corporation

• Kidney Diseases

  Major

  The use of cyclosporine is contraindicated in patients with rheumatoid arthritis or psoriasis with abnormal renal function. Cyclosporine causes a reversible reduction in renal blood flow and glomerular filtration rate resulting in increased serum creatinine and blood urea nitrogen. Mild nephrotoxicity generally responds to reductions in cyclosporine doses. Persistent, chronic, and progressive nephrotoxicity has occurred. Renal biopsies from these patients can demonstrate interstitial fibrosis, tubular atrophy, global or segmental glomerulosclerosis, or smooth vascular muscle damage. Larger cumulative doses or elevated cyclosporine trough levels may be associated with the development of interstitial fibrosis. Clinical monitoring of renal function is necessary and differentiation between cyclosporine-induced nephrotoxicity, allograft rejection, and other causes of impaired renal function should be determined prior to cyclosporine dosage adjustments.

  29 sources

  1. Harris KP, Jenkins D, Walls J "Nonsteroidal antiinflammatory drugs and cyclosporine: a potentially serious adverse interaction." Transplantation 46 (1988): 598-9
  2. Bertani T, Ferrazzi P, Schieppati A, et al. "Nature and extent of glomerular injury induced by cyclosporine in heart transplant patients." Kidney Int 40 (1991): 243-50
  3. Madhok R, Torley HI, Capell HA "A study of the longterm efficacy and toxicity of cyclosporine A in rheumatoid arthritis." J Rheumatol 18 (1991): 1485-9
  4. Ballardie FW, Edwards BD, Hows J, et al. "Disturbance in renal haemodynamics and physiology in bone marrow transplant recipients treated with ciclosporin A." Nephron 60 (1992): 17-24
  5. Butkus DE, Herrera GA, Raju SS "Successful renal transplantation after cyclosporine-associated hemolytic-uremic syndrome following bilateral lung transplantation." Transplantation 54 (1992): 159-62
  6. Margolis DJ, Guzzo C, Johnson J, Lazarus GS "Alterations in renal function in psoriasis patients treated with cyclosporine, 5 mg/kg/day." J Am Acad Dermatol 26 (1992): 195-7
  7. Zachariae H, Hansen HE, Kragballe K, Olsen S "Morphologic renal changes during cyclosporine treatment of psoriasis." J Am Acad Dermatol 26 (1992): 415-9
  8. Burack DA, Griffith BP, Thompson ME, Kahl LE "Hyperuricemia and gout among heart transplant recipients receiving cyclosporine." Am J Med 92 (1992): 141-6

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  9. Venkataramanan R, Ptachcinski RJ, Burckart GJ, et al. "The clearance of cyclosporine by hemodialysis." J Clin Pharmacol 24 (1984): 528-31
  10. Albrecht K, Niebel W, Marggraf G, Eigler FW "Cyclosporine pharmacokinetics in the early course of renal transplantation." Transplant Proc 19 (1987): 17-9
  11. Dische FE, Neuberger J, Keating J, et al. "Kidney pathology in liver allograft recipients after long-term treatment with cyclosporin A." Lab Invest 58 (1988): 395-402
  12. Awni WM, Kasiske BL, Heim-Duthoy K, Rao KV "Long-term cyclosporine pharmacokinetic changes in renal transplant recipients: effects of binding and metabolism." Clin Pharmacol Ther 45 (1989): 41-8
  13. Vernillet L, Moulin B, Dadoun C, et al. "Pharmacokinetics of cyclosporine A in patients with nephrotic syndrome." Transplant Proc 20 (1988): 529-35
  14. Morales JM, Andres A, Hernandez E, et al. "Fractional excretion of sodium is an early predictor of cyclosporine nephrotoxicity after renal transplantation." Transplant Proc 22 (1990): 1728-9
  15. Bach JF, Feutren G, Noel LH, et al. "Factors predictive of cyclosporine-induced nephrotoxicity: the role of cyclosporine blood levels." Transplant Proc 22 (1990): 1296-8
  16. Frey FJ "Pharmacokinetic determinants of cyclosporine and prednisone in renal transplant patients." Kidney Int 39 (1991): 1034-50
  17. Cantarell MC, Capdevila L, Morlans M, Piera L "Uric acid calculus in renal transplant patients treated with cyclosporine." Clin Nephrol 35 (1991): 288
  18. Dijkmans BA, van Rijthoven AW, The HS, et al. "Effect of cyclosporin on serum creatinine in patients with rheumatoid arthritis." Eur J Clin Pharmacol 31 (1987): 541-5
  19. Follath F, Wenk M, Vozeh S, et al. "Intravenous cyclosporine kinetics in renal failure." Clin Pharmacol Ther 34 (1983): 638-43
  20. Boers M, van Rijthoven AW, The HS, et al. "Serum creatinine levels two years later: follow-up of a placebo-controlled trial of cyclosporine in rheumatoid patients." Transplant Proc 20 (1988): 371-5
  21. Ludwin D, Bennett KJ, Grace EM, et al. "Nephrotoxicity in patients with rheumatoid arthritis treated with cyclosporine." Transplant Proc 20 (1988): 367-70
  22. Messana JM, Rocher LL, Ellis CN, et al. "Effects of cyclosporine on renal function in psoriasis patients." J Am Acad Dermatol 23 (1990): 1288-93
  23. Ptachcinski RJ, Venkataramanan R, Rosenthal JT, Burckart GJ, Taylor RJ, Hakala TR "Cyclosporine kinetics in renal transplantation." Clin Pharmacol Ther 38 (1985): 296-300
  24. "Product Information. SandIMMUNE (cycloSPORINE)." Apothecon Inc (2022):
  25. Landewe RBM, The HSG, Vanrijthoven AWAM, Rietveld JR, Breedveld FC, Dijkmans BAC "Cyclosporine in common clinical practice: an estimation of the benefit/risk ratio in patients with rheumatoid arthritis." J Rheumatol 21 (1994): 1631-6
  26. Forre O, Bjerkhoel F, Kjeldsenkragh J, Ostensen H, Astor T, Boe E, Lekven C, Sorensen JU, Karoliussen O, Dehli O, Glennas A, Kv "Radiologic evidence of disease modification in rheumatoid arthritis patients treated with cyclosporine - results of a 48-week multicenter study comparing low-dose cyclosporine with placebo." Arthritis Rheum 37 (1994): 1506-12
  27. Bensen W, Tugwell P, Roberts RM, Ludwin D, Ross H, Grace E, Gent M "Combination therapy of cyclosporine with methotrexate and gold in rheumatoid arthritis (2 pilot studies)." J Rheumatol 21 (1994): 2034-8
  28. "Product Information. Neoral (cycloSPORINE)." Sandoz Pharmaceuticals Corporation
  29. Neumayer HH, Budde K, Farber L, Haller P, Kohnen R, Maibucher A, Schuster A, Vollmar J, Waiser J, Luft FC "Conversion to microemulsion cyclosporine in stable renal transplant patients: results after one year." Clin Nephrol 45 (1996): 326-31

• Liver Diseases

  Moderate

  Cyclosporine is extensively metabolized by CYP450 3A enzymes in the liver (some GI and renal metabolism) and primarily eliminated in the bile and feces. Cyclosporine can induce dose-related nephrotoxicity and hepatotoxicity. Hepatotoxicity, usually noted during the first month of therapy (high dosages) is characterized by elevations of hepatic enzymes and bilirubin. Reduction in chemistry levels usually results with dosage reduction. Therapy with cyclosporine should be administered cautiously and dosages modifications considered in patients with or predisposed to hepatic dysfunction. Clinical monitoring of hepatic function, particularly during administration of high dosages, is recommended.

  10 sources

  1. Christians U, Kohlhaw K, Budniak J, et al. "Ciclosporin metabolite pattern in blood and urine of liver graft recipients." Eur J Clin Pharmacol 41 (1991): 285-90
  2. Takaya S, Zaghloul I, Iwatsuki S, et al. "Effect of liver dysfunction on cyclosporine pharmacokinetics." Transplant Proc 19 (1987): 1246-7
  3. Awni WM, Kasiske BL, Heim-Duthoy K, Rao KV "Long-term cyclosporine pharmacokinetic changes in renal transplant recipients: effects of binding and metabolism." Clin Pharmacol Ther 45 (1989): 41-8
  4. de Groen PC, McCallum DK, Moyer TP, Wiesner RH "Pharmacokinetics of cyclosporine in patients with primary biliary cirrhosis." Transplant Proc 20 (1988): 509-11
  5. Vernillet L, Moulin B, Dadoun C, et al. "Pharmacokinetics of cyclosporine A in patients with nephrotic syndrome." Transplant Proc 20 (1988): 529-35
  6. Kassianides C, Nussenblatt R, Palestine AG, et al. "Liver injury from cyclosporine A." Dig Dis Sci 35 (1990): 693-7
  7. Sewing K-F, Christians U, Kohlhaw K, et al. "Biologic activity of cyclosporine metabolites." Transplant Proc 22 (1990): 1129-34
  8. "Product Information. SandIMMUNE (cycloSPORINE)." Apothecon Inc (2022):

  Show all 10 sourcesShow fewer sources

  9. "Product Information. Neoral (cycloSPORINE)." Sandoz Pharmaceuticals Corporation
  10. Tredger JM "Using cyclosporine neoral immediately after liver transplantation." Ther Drug Monit 17 (1995): 638-41

• Malabsorption Syndromes

  Moderate

  Patients with malabsorption syndromes may have difficulty achieving therapeutic serum concentrations with the Sandimmune formulations (capsules or solution) of cyclosporine. An alternative formulation, Neoral (capsule or solution for microemulsion), has increased bioavailability compared to Sandimmune. Sandimmune and Neoral are not bioequivalent and should not be used interchangeably without physician supervision.

  6 sources

  1. Albrecht K, Niebel W, Marggraf G, Eigler FW "Cyclosporine pharmacokinetics in the early course of renal transplantation." Transplant Proc 19 (1987): 17-9
  2. de Groen PC, McCallum DK, Moyer TP, Wiesner RH "Pharmacokinetics of cyclosporine in patients with primary biliary cirrhosis." Transplant Proc 20 (1988): 509-11
  3. Vernillet L, Moulin B, Dadoun C, et al. "Pharmacokinetics of cyclosporine A in patients with nephrotic syndrome." Transplant Proc 20 (1988): 529-35
  4. "Product Information. SandIMMUNE (cycloSPORINE)." Apothecon Inc (2022):
  5. "Product Information. Neoral (cycloSPORINE)." Sandoz Pharmaceuticals Corporation
  6. "Product Information. Neoral (cycloSPORINE)." Sandoz Pharmaceuticals Corporation