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Drug Interactions between Adriamycin RDF and Sandimmune

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

cycloSPORINE DOXOrubicin

Applies to: Sandimmune (cyclosporine) and Adriamycin RDF (doxorubicin)

ADJUST DOSE: Cyclosporine can significantly decrease plasma clearance both of doxorubicin and of its main metabolite, doxorubicinol. In resistant cells, intracellular accumulation of doxorubicin does not occur because the multidrug resistance-1 (MDR-1) gene product, a membrane glycoprotein, is an energy-dependent efflux pump. Cyclosporine blocks the function of this pump, allowing a greater intracellular accumulation of some cytotoxic agents.

MANAGEMENT: This interaction may be used to clinical advantage in the treatment of cancer. If cyclosporine is used to decrease tumor cell resistance to doxorubicin, it is recommended that doxorubicin dosage be reduced to approximately 50% to 60% of the normally recommended dosage.

References

  1. Shoji Y, Fisher MH, Periasamy A, et al. (1991) "Verapamil and cyclosporin A modulate doxorubicin toxicity by distinct mechanisms." Cancer Lett, 57, p. 209-18
  2. Barbui T, Rambaldi A, Parenzan L, Zucchelli M, Perico N, Remuzzi G (1992) "Neurological symptoms and coma associated with doxorubicin administration during chronic cyclosporin therapy." Lancet, 339, p. 1421
  3. Rushing DA, Raber SR, Rodvold KA, Piscitelli SC, Plank GS, Tewksbury DA (1994) "The effects of cyclosporine on the pharmacokinetics of doxorubicin in patients with small cell lung cancer." Cancer, 74, p. 834-41
  4. Bartlett NL, Lum BL, Fisher GA, Brophy NA, Ehsan MN, Halsey J, Sikic BI (1994) "Phase I trial of doxorubicin with cyclosporine as a modulator of multidrug resistance." J Clin Oncol, 12, p. 835-42
  5. Bartlett NL, Fisher GA, Halsey J, Ehsan MN, Lum BL, Sikic BI (1993) "A Phase I trial of doxorubicin (D) with cyclosporine (CsA) as a modulator of multidrug resistance (MDR)." Proc Annu Meet Am Soc Clin Oncol, 12, a366
  6. Hu XF, Martin TJ, Bell DR, de Luise M, Zalcberg JR (1990) "Combined use of cyclosporin A and verapamil in modulating multidrug resistance in human leukemia cell lines." Cancer Res, 50, p. 2953-7
  7. Sonneveld P, Durie BG, Lokhorst HM, Marie JP, Solbu G, et al. (1992) "Modulation of multidrug-resistant multiple myeloma by cyclosporin. The Leukaemia Group of the EORTC and the HOVON." Lancet, 340, p. 255-9
  8. Larsson R, Bergh J, Nygren P (1991) "Combination of cyclosporin A and buthionine sulfoximine (BSO) as a pharmacological strategy for circumvention of multidrug resistance in small cell lung cancer cell lines selected for resistance to doxorubicin." Anticancer Res, 11, p. 455-9
  9. Tidefelt U, Juliusson G, Elmhorn-Rosenborg A, Peterson C, Paul C (1994) "Increased intracellular concentrations of doxorubicin in resistant lymphoma cells in vivo by concomitant therapy with verapamil and cyclosporin A." Eur J Haematol, 52, p. 276-82
  10. Klaff RA (1995) "The effects of cyclosporine on the pharmacokinetics of doxorubicin in patients with small cell lung cancer." Cancer, 75, p. 1215-6
  11. Colombo T, Zucchetti M, D'Incalci M (1994) "Cyclosporin A markedly changes the distribution of doxorubicin in mice and rats." J Pharmacol Exp Ther, 269, p. 22-7
  12. Scheulen ME, Budach W, Skorzec M, Wiefelsputz JK, Seeber S (1993) "Influence of cyclosporin A on the pharmacokinetics and pharmacodynamics of doxorubicin (Meeting abstract)." Proc Annu Meet Am Assoc Cancer Res, 34, a12711993
View all 12 references

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Drug and food interactions

Moderate

cycloSPORINE food

Applies to: Sandimmune (cyclosporine)

GENERALLY AVOID: 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.

GENERALLY AVOID: Administration with red wine or purple grape juice may decrease blood concentrations of cyclosporine. In 12 healthy volunteers, 12 ounces total of a merlot consumed 15 minutes prior to and during cyclosporine administration (single 8 mg/kg dose of Sandimmune) decreased cyclosporine peak blood concentration (Cmax) and systemic exposure (AUC) by 38% and 30%, respectively, compared to water. The time to reach peak concentration (Tmax) doubled, and oral clearance increased 50%. Similarly, one study were 12 healthy patients were administered purple grape juice and a single dose of cyclosporine showed a 30% and a 36% decrease in cyclosporine systemic exposure (AUC) and peak blood concentration (Cmax), respectively. The exact mechanism of interaction is unknown but may involve decreased cyclosporine absorption.

MONITOR: Food has been found to have variable effects on the absorption of cyclosporine. There have been reports of impaired, unchanged, and enhanced absorption during administration with meals relative to the fasting state. The mechanisms are unclear. Some investigators found an association with the fat content of food. In one study, increased fat intake resulted in significantly increased cyclosporine bioavailability and clearance. However, the AUC and pharmacodynamics of cyclosporine were not significantly affected, thus clinical relevance of these findings may be minimal.

MANAGEMENT: 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.

References

  1. Honcharik N, Yatscoff RW, Jeffery JR, Rush DN (1991) "The effect of meal composition on cyclosporine absorption." Transplantation, 52, p. 1087-9
  2. Ducharme MP, Provenzano R, Dehoornesmith M, Edwards DJ (1993) "Trough concentrations of cyclosporine in blood following administration with grapefruit juice." Br J Clin Pharmacol, 36, p. 457-9
  3. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  4. Hollander AAMJ, Vanrooij J, Lentjes EGWM, Arbouw F, Vanbree JB, Schoemaker RC, Vanes LA, Vanderwoude FJ, Cohen AF (1995) "The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients." Clin Pharmacol Ther, 57, p. 318-24
  5. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  6. Tan KKC, Trull AK, Uttridge JA, Metcalfe S, Heyes CS, Facey S, Evans DB (1995) "Effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine in kidney transplant recipients." Clin Pharmacol Ther, 57, p. 425-33
  7. Yee GC, Stanley DL, Pessa LJ, et al. (1995) "Effect of grrapefruit juice on blood cyclosporin concentration." Lancet, 345, p. 955-6
  8. Ducharme MP, Warbasse LH, Edwards DJ (1995) "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice." Clin Pharmacol Ther, 57, p. 485-91
  9. Ioannidesdemos LL, Christophidis N, Ryan P, Angelis P, Liolios L, Mclean AJ (1997) "Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases." J Rheumatol, 24, p. 49-54
  10. Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF, Hunsicker LG (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients." Transplantation, 62, p. 123-5
  11. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  12. Tsunoda SM, Harris RZ, Christians U, et al. (2001) "Red wine decreases cyclosporine bioavailability." Clin Pharmacol Ther, 70, p. 462-7
  13. Oliveira-Freitas VL, Dalla Costa T, Manfro RC, Cruz LB, Schwartsmann G (2010) "Influence of purple grape juice in cyclosporine availability." J Ren Nutr, 20, p. 309-13
View all 13 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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