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Drug Interactions between sunitinib and Tolsura

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

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Interactions between your drugs

Moderate

itraconazole SUNItinib

Applies to: Tolsura (itraconazole) and sunitinib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of sunitinib and its pharmacologically active metabolite, both of which are substrates of the isoenzyme. In healthy volunteers, concurrent administration of a single dose of sunitinib with the potent CYP450 3A4 inhibitor, ketoconazole, resulted in a 49% and 51% increase in the combined (i.e., sunitinib plus its primary active metabolite) peak plasma concentration (Cmax) and systemic exposure (AUC) values, respectively, compared to administration of sunitinib alone. Because sunitinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Alternative agents with no or minimal CYP450 3A4-inhibiting activity are recommended in patients treated with sunitinib. Some authorities recommend avoiding concomitant use of sunitinib during and for 2 weeks after treatment with itraconazole. A dose reduction for sunitinib to a minimum of 37.5 mg daily for gastrointestinal stromal tumor (GIST) and metastatic renal cell carcinoma (mRCC) or 25 mg daily for pancreatic neuroendocrine tumors (pNET) should be considered if it must be coadministered with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, nefazodone, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics.

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. (2006) "Product Information. Sutent (sunitinib)." Pfizer U.S. Pharmaceuticals Group
  3. Cerner Multum, Inc. "Australian Product Information."

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Drug and food interactions

Moderate

itraconazole food

Applies to: Tolsura (itraconazole)

ADJUST DOSING INTERVAL: Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution. Cola beverages may increase the bioavailability of itraconazole capsules. Itraconazole capsules require an acidic gastric pH for adequate dissolution and subsequent absorption. Cola beverages help lower gastric pH and improve absorption.

GENERALLY AVOID: Grapefruit juice may impair the absorption of itraconazole capsules, resulting in decreased antifungal effects. In a small, randomized, crossover study, the administration of itraconazole capsules with double-strength grapefruit juice (compared to water) was associated with significantly decreased (43%) plasma concentrations of itraconazole and its pharmacologically active hydroxy metabolite, as well as delayed times to reach peak concentrations of both. The exact mechanism of interaction is unknown but may involve reduced absorption of itraconazole secondary to enhanced activity of intestinal P-glycoprotein drug efflux pumps and delayed gastric emptying induced by certain compounds present in grapefruits. Another study reported no pharmacokinetic changes with single-strength grapefruit juice. Whether or not these observations apply to itraconazole oral solution is unknown.

MANAGEMENT: The manufacturer recommends that the capsules be taken immediately after a full meal and the solution be taken on an empty stomach to ensure maximal absorption. Cola beverages may help increase the bioavailability of itraconazole capsules, particularly in patients with hypochlorhydria or those treated concomitantly with gastric acid suppressants. Until more information is available, it may be advisable to avoid the consumption of grapefruits and grapefruit juice during itraconazole therapy.

References

  1. Van Peer A, Woestenborghs R, Heykants J, et al. (1989) "The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects." Eur J Clin Pharmacol, 36, p. 423-6
  2. Wishart JM (1987) "The influence of food on the pharmacokinetics of itraconazole in patients with superficial fungal infection." J Am Acad Dermatol, 17, p. 220-3
  3. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  4. Barone JA, Koh JG, Bierman RH, Colaizzi JL, Swanson KA, Gaffar MC, Moskovitz BL, Mechlinski W, Van de Velde V (1993) "Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers." Antimicrob Agents Chemother, 37, p. 778-84
  5. Zimmermann T, Yeates RA, Albrecht M, Laufen H, Wildfeuer A (1994) "Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in japanese subjects." Int J Clin Pharmacol Res, 14, p. 87-93
  6. (2022) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  7. Kawakami M, Suzuki K, Ishizuka T, Hidaka T, Matsuki Y, Nakamura H (1998) "Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects." Int J Clin Pharmacol Ther, 36, p. 306-8
  8. Barone JA, Moskotitz BL, Guarnieri J, Hassell AE, Colaizzi JL, Bierman RH, Jessen L (1998) "Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers." Pharmacotherapy, 18, p. 295-301
  9. Penzak SR, Gubbins PO, Gurley BJ, Wang PL, Saccente M (1999) "Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers." Ther Drug Monit, 21, p. 304-9
  10. Katz HI (1999) "Drug interactions of the newer oral antifungal agents." Br J Dermatol, 141, p. 26-32
View all 10 references

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Moderate

SUNItinib food

Applies to: sunitinib

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during sunitinib therapy may increase the plasma concentrations of sunitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of large amounts of grapefruit or grapefruit juice during sunitinib therapy.

References

  1. (2006) "Product Information. Sutent (sunitinib)." Pfizer U.S. Pharmaceuticals Group

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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.

Further information

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