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Drug Interactions between Nizoral and Prilosec

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

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Interactions between your drugs

Moderate

ketoconazole omeprazole

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

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Drug and food interactions

Moderate

ketoconazole food

Applies to: Nizoral (ketoconazole)

GENERALLY AVOID: Excessive use of alcohol or products containing alcohol together with ketoconazole or levoketoconazole may potentiate the risk of liver injury. Serious hepatotoxicity has been reported with levoketoconazole. Hepatotoxicity requiring liver transplantation has been reported with the use of oral ketoconazole, of which levoketoconazole is an enantiomer. Some patients had no obvious risk factors for liver disease. In addition, use of alcohol or products containing alcohol during ketoconazole or levoketoconazole therapy may result in a disulfiram-like reaction in some patients. Symptoms of disulfiram-like reaction include flushing, rash, peripheral edema, nausea, and headache.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of ketoconazole or levoketoconazole. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

When administered to healthy volunteers with a high-fat meal (875 calories; 62% fat), levoketoconazole systemic exposure (AUC) increased by 30% while peak plasma concentration (Cmax) did not change and the time to reach Cmax (Tmax) was delayed from 2 to 4 hours, compared to fasted conditions.

MANAGEMENT: Levoketoconazole may be administered with or without food. Excessive consumption of alcohol should generally be avoided during ketoconazole or levoketoconazole therapy. Patients should preferably avoid or limit consumption of grapefruit, grapefruit juice, or any supplement containing grapefruit extract during ketoconazole or levoketoconazole therapy. Patients receiving ketoconazole or levoketoconazole should be instructed to contact their doctor immediately if they experience swelling, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage.

References

  1. (2019) "Product Information. Ketoconazole (ketoconazole)." Mylan Pharmaceuticals Inc
  2. (2022) "Product Information. Recorlev (levoketoconazole)." Xeris Pharmaceuticals Inc
  3. Auchus R, Pivonello R, Fleseriu M, et al. (2022) Levoketoconazole: a novel treatment for endogenous Cushing's syndrome. https://www.tandfonline.com/doi/pdf/10.1080/17446651.2021.1945440
  4. (2021) "Product Information. Ketoconazole (ketoconazole)." Burel Pharmaceuticals Inc
View all 4 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.

See also

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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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