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Drug Interactions between cyclosporine and Prezista

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

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Interactions between your drugs

Major

cycloSPORINE darunavir

Applies to: cyclosporine and Prezista (darunavir)

MONITOR CLOSELY: Coadministration with protease inhibitors (PIs), especially ritonavir, may significantly increase the blood concentrations of cyclosporine. The risk of nephro- and neurotoxicity associated with cyclosporine may be increased. The mechanism involves PI inhibition of CYP450 3A4, the isoenzyme responsible for the intestinal and hepatic metabolism of cyclosporine. Enhanced cyclosporine oral bioavailability due to PI inhibition of intestinal P-glycoprotein efflux transporter may also contribute. In an HIV+ renal transplant patient whose treatment regimen included cyclosporine (150 mg twice a day) prednisone, zidovudine and lamivudine, trough cyclosporine levels that had been stable in the 150 to 200 mcg/L range rose to 580 mcg/L three days after saquinavir therapy (1200 mg three times a day) was added. The patient reported fatigue, headache, and gastrointestinal discomfort. The dosage of both cyclosporine and saquinavir were subsequently reduced by 50%, which yielded a systemic exposure (AUC) of cyclosporine approximating that measured when cyclosporine was given at the original dose before saquinavir. However, saquinavir AUC was 11 times that reported in historical controls.

MANAGEMENT: Caution is advised if cyclosporine is used in combination with protease inhibitors. Cyclosporine blood levels and renal function should be checked frequently and the dosage adjusted accordingly, particularly following initiation or discontinuation of PI therapy in patients who are stabilized on their cyclosporine regimen. Patients should be advised to notify their physician if they experience possible signs of cyclosporine toxicity such as nausea, vomiting, diarrhea, abdominal pain, dizziness, fatigue, headache, tremors, and convulsions. Patients treated with saquinavir should also be monitored for potential PI toxicity and the dosage adjusted accordingly.

References

  1. "Product Information. Neoral (cycloSPORINE)." Sandoz Pharmaceuticals Corporation
  2. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  3. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  4. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  5. Brinkman K, Huysmans F, Burger DM (1998) "Pharmacokinetic interaction between saquinavir and cyclosporine." Ann Intern Med, 129, p. 914-5
  6. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  7. (2001) "Product Information. Fortovase (saquinavir)." Roche Laboratories
  8. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  9. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  10. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
View all 10 references

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Drug and food interactions

Moderate

cycloSPORINE food

Applies to: 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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Moderate

darunavir food

Applies to: Prezista (darunavir)

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

References

  1. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc

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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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