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Drug Interactions between etoposide and Tolsura

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

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Interactions between your drugs

Moderate

itraconazole etoposide

Applies to: Tolsura (itraconazole) and etoposide

MONITOR: Coadministration with itraconazole may significantly increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by itraconazole.

MANAGEMENT: Caution is advised if itraconazole must be used concomitantly with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever itraconazole is added to or withdrawn from therapy. Some authorities recommend avoiding concomitant use of nevirapine from 2 weeks before and during treatment with itraconazole.

References

  1. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  2. Tailor SAN "Peripheral edema due to nifedipine-itraconazole interaction: a case report." Arch Dermatol 132 (1996): 1374
  3. Chiba M, Hensleigh M, Nishime JA, Balani SK, Lin JH "Role of cytochrome P450 3A4 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor." Drug Metab Dispos 24 (1996): 307-14
  4. Gillies J, Hung KA, Fitzsimons E, Soutar R "Severe vincristine toxicity in combination with itraconazole." Clin Lab Haematol 20 (1998): 123-4
  5. Kaukonen KM, Olkkola KT, Neuvonen PJ "Itraconazole increases plasma concentrations of quinidine." Clin Pharmacol Ther 62 (1997): 510-7
  6. Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ "Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole." Clin Pharmacol Ther 64 (1998): 363-8
  7. Lukkari E, Juhakoski A, Aranko K, Neuvonen PJ "Itraconazole moderately increases serum concentrations of oxybutynin but does not affect those of the active metabolite." Eur J Clin Pharmacol 52 (1997): 403-6
  8. Auclair B, Berning SE, Huitt GA, Peloquin CP "Potential interaction between itraconazole and clarithromycin." Pharmacotherapy 19 (1999): 1439-44
  9. Cerner Multum, Inc. "Australian Product Information." O 0
View all 9 references

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