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Drug Interactions between itraconazole and omeprazole

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

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Interactions between your drugs

Moderate

itraconazole omeprazole

Applies to: itraconazole and omeprazole

GENERALLY AVOID: Inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may decrease the gastrointestinal absorption of the azole antifungal agents, itraconazole (capsules only) and ketoconazole, both of which require an acidic environment for dissolution. By increasing gastric pH and reducing the acidity, proton pump inhibitors can decrease bioavailability of the azoles by 75% to 80%. Additionally, ketoconazole (a potent CYP450 3A4 inhibitor) may increase serum omeprazole levels. The metabolism of omeprazole includes hydroxylation catalyzed by CYP450 2C19 and, to a minor extent, sulfoxidation by CYP450 3A4. In a study involving ten subjects, ketoconazole 100 mg to 200 mg daily resulted in a marked inhibition of the formation of the omeprazole sulfone in both extensive and poor metabolizers of CYP450 2C19. In poor metabolizers, a doubling of omeprazole levels was observed. No adverse effects were reported by any of the subjects.

MANAGEMENT: In general, the concomitant use of these drugs is not recommended. If coadministration is necessary, an acidic pH may be produced with two capsules of glutamic acid hydrochloride administered 15 minutes before the azole dose. Administration with an acidic beverage such as Coca-Cola(R) may also help. Additionally, an increase of the antifungal dosage may be required. However, clinicians should still consider the possibility of a reduced or subtherapeutic antifungal effect. It may be appropriate to switch to itraconazole oral solution or an agent like fluconazole whose absorption is not affected by stomach pH.

References

  1. Piscitelli SC, Goss TF, Wilton JH, D'Andrea DT, Goldstein H, Schentag JJ "Effects of ranitidine and sucralfate on ketoconazole bioavailability." Antimicrob Agents Chemother 35 (1991): 1765-71
  2. Van der Meer JW, Keuning JJ "The influence of gastric acidity on the bio-availability of ketoconazole." J Antimicrob Chemother 6 (1980): 552-4
  3. Carlson JA, Mann HJ, Canafax DM "Effect of pH on disintegration and dissolution of ketoconazole tablets." Am J Hosp Pharm 40 (1983): 1334-6
  4. "Product Information. PriLOSEC (omeprazole)." Merck & Co., Inc (2022):
  5. "Product Information. Prevacid (lansoprazole)." TAP Pharmaceuticals Inc PROD (2001):
  6. Chin TWF, Loeb M, Fong IW "Effects of an acidic beverage (coca-cola) on absorption of ketoconazole." Antimicrob Agents Chemother 39 (1995): 1671-5
  7. Jaruratanasirikul S, Sriwiriyajan S "Effect of omeprazole on the pharmacokinetics of itraconazole." Eur J Clin Pharmacol 54 (1998): 159-61
  8. Bottiger Y, Tybring G, Gotharson E, Bertilsson L "Inhibition of the sulfoxidation of omeprazole by ketoconazole in poor and extensive metabolizers of S-mephenytoin." Clin Pharmacol Ther 62 (1997): 384-91
  9. "Product Information. Aciphex (rabeprazole)." Janssen Pharmaceuticals PROD (2001):
  10. Katz HI "Drug interactions of the newer oral antifungal agents." Br J Dermatol 141 (1999): 26-32
  11. "Product Information. Protonix (pantoprazole)." Wyeth-Ayerst Laboratories PROD (2001):
  12. "Product Information. Nexium (esomeprazole)." Astra-Zeneca Pharmaceuticals PROD (2001):
  13. "Product Information. Voquezna Dual Pak (amoxicillin-vonoprazan)." Phathom Pharmaceuticals, Inc ORIG-1 (2022):
  14. "Product Information. Voquezna Triple Pak (amoxicillin/clarithromycin/vonoprazan)." Phathom Pharmaceuticals, Inc ORIG-1 (2022):
View all 14 references

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Drug and food interactions

Moderate

itraconazole food

Applies to: 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.

Further information

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