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Drug Interactions between rifapentine and Sandimmune

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

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Interactions between your drugs

Major

cycloSPORINE rifapentine

Applies to: Sandimmune (cyclosporine) and rifapentine

MONITOR CLOSELY: The coadministration with rifamycins, particularly rifampin, may decrease the blood concentrations and pharmacologic effects of cyclosporine. The mechanism probably involves reduced absorption as well as accelerated clearance of cyclosporine due to induction of both intestinal P-glycoprotein drug efflux pumps and hepatic/intestinal CYP450 3A4 isoenzymes by rifamycins. In a study of six healthy volunteers, rifampin (600 mg orally at bedtime for 11 days) increased the average blood clearance of cyclosporine (10 mg/kg orally and 3 mg/kg intravenously) by 40% and decreased its oral bioavailability from 27% to 10%. There have also been case reports of transplant patients whose cyclosporine blood levels dropped significantly, often below assay detection limits, as early as two days following the initiation of rifampin. The decreases were associated with acute rejection episodes in many cases, subsequently requiring discontinuation of rifampin or substantial increases in cyclosporine dosage. This interaction is likely to occur with other rifamycins but to a lesser extent. In vitro and in vivo enzyme studies have suggested rifapentine induction potential to be less than that of rifampin but greater than that of rifabutin.

MANAGEMENT: Given the risk of organ rejection associated with inadequate immunosuppressant levels, caution is advised if cyclosporine must be coadministered with rifamycins, particularly rifampin. Cyclosporine blood levels should be closely monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of rifamycin therapy in patients who are stabilized on their anti-rejection regimen.

References

  1. Howard P, Bixler TJ, Gill B (1985) "Cyclosporine-rifampin drug interaction." Drug Intell Clin Pharm, 19, p. 763-4
  2. Vandevelde C, Chang A, Andrews D, et al. (1991) "Rifampin and ansamycin interaction with cyclosporine after renal transplantation." Pharmacotherapy, 11, p. 88-9
  3. Al-Sulaiman MH, Dhar JM, Al-Khader AA (1990) "Successful use of rifampicin in the treatment of tuberculosis in renal transplant patients immunosuppressed with cyclosporine." Transplantation, 50, p. 597-8
  4. Yee GC, McGuire TR (1990) "Pharmacokinetic drug interactions with cyclosporin (Part I)." Clin Pharmacokinet, 19, p. 319-32
  5. Daniels NJ, Dover JS, Schachter RK (1984) "Interaction between cyclosporin and rifampicin." Lancet, 1, p. 639
  6. Langhoff E, Madsen S (1983) "Rapid metabolism of cyclosporin and prednisone in kidney transplant patient receiving tuberculostatic treatment." Lancet, 2, p. 1031
  7. Offermann G, Keller F, Molzahn M (1985) "Low cyclosporine A blood levels and acute graft rejection in a renal transplant recipient during rifampin treatment." Am J Nephrol, 5, p. 385-7
  8. Allen RD, Hunnisett AG, Morris PJ (1985) "Cyclosporin and rifampicin in renal transplantation." Lancet, 1, p. 980
  9. Cassidy MJ, Zyl-Smit RV, Pascoe MD, et al. (1985) "Effect of rifampicin on cyclosporin A blood levels in a renal transplant recipient." Nephron, 41, p. 207-8
  10. (2022) "Product Information. SandIMMUNE (cycloSPORINE)." Apothecon Inc
  11. Van Buren D, Wideman CA, Ried M, et al. (1984) "The antagonistic effect of rifampin upon cyclosporin bioavailability." Transplant Proc, 16, p. 1642-5
  12. Calne RY, White DJG, Thiru S, Rolles K, Drakopoulos S, Jamieson NV (1985) "Cyclosporin and antituberculous therapy." Lancet, 1, p. 1342-3
  13. Modry DL, Stinson EB, Oyer PE, Jamieson SW, Baldwin JC, Shumway NE (1985) "Acute rejection and massive cyclosporin requirements in heart transplant recipients treated with rifampin." Transplantation, 39, p. 313-4
  14. Koselj M, Bren A, Kandus A, Kovac D (1994) "Drug interactions between cyclosporine and rifampicin, erythromycin, and azoles in kidney recipients with opportunistic infections." Transplant Proc, 26, p. 2823-4
  15. Zylber-Katz E (1995) "Multiple drug interactions with cyclosporine in a heart transplant patient." Ann Pharmacother, 29, p. 127-31
  16. Hebert MF, Roberts JP, Prueksaritanont T, Benet LZ (1992) "Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction." Clin Pharmacol Ther, 52, p. 453-7
  17. Watkins PB (1992) "Drug metabolism by cytochromes P450 in the liver and small bowel." Gastroenterol Clin North Am, 21, p. 511-26
  18. Strayhorn VA, Baciewicz AM, Self TH (1997) "Update on rifampin drug interactions, III." Arch Intern Med, 157, p. 2453-8
View all 18 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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Moderate

rifapentine food

Applies to: rifapentine

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.

References

  1. (2021) "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India), 2
  2. (2021) "Product Information. Priftin (rifapentine)." sanofi-aventis

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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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