Omeprazole with Voriconazole Interaction Details

Brand Names Associated with Omeprazole

Brand Names Associated with Voriconazole

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 05, 2023

Interaction Effect

Increased plasma concentrations of omeprazole

Interaction Summary

Avoid concomitant use of omeprazole with voriconazole. Omeprazole is metabolized by CYP2C19 and CYP3A4. Concomitant administration with voriconazole, a strong inhibitor of CYP2C19 and CYP3A4, may cause increased omeprazole plasma levels. The manufacturers of voriconazole recommend a 50% omeprazole dose reduction if voriconazole is added in patients receiving omeprazole 40 mg/day or greater . Omeprazole dose adjustments are not recommended by the manufacturers of omeprazole; although, a dose adjustment may be considered in patients with Zollinger-Ellison's syndrome when higher omeprazole doses are used (up to 240 mg/day) . Monitor patients for increased omeprazole adverse events (eg, elevated liver enzymes, headache, diarrhea, abdominal pain) if omeprazole and voriconazole are administered together .

Severity

Major

Onset

Rapid

Evidence

Established

How To Manage Interaction

Avoid concomitant use of omeprazole with voriconazole. If omeprazole is coadministered with a strong CYP2C19 and CYP3A4 inhibitor, such as voriconazole, this may lead to increased omeprazole plasma levels. According to the omeprazole manufacturer, when voriconazole and omeprazole are used concurrently, omeprazole dosage adjustment may be considered in patients with Zollinger-Ellison's syndrome when higher doses (up to 240 mg/day) are used . However, the voriconazole manufacturer recommends that the omeprazole dose be reduced by one-half when initiating voriconazole therapy in patients receiving omeprazole doses of 40 mg or greater. No dose adjustment of voriconazole is required . Monitor patients for increased omeprazole adverse events (eg, elevated liver enzymes, headache, diarrhea, abdominal pain).

Mechanism Of Interaction

Inhibition of CYP2C19- and CYP3A4-mediated omeprazole metabolism by voriconazole

Literature Reports

A) An open, randomized, placebo-controlled, cross-over study using healthy volunteers (n=18) found that the coadministration of omeprazole and voriconazole increased voriconazole Cmax and AUC concentrations; however, omeprazole had no clinically relevant effect on voriconazole exposure and no voriconazole dose adjustment is necessary. Healthy male volunteers (mean age, 26.3 years, range, 20 to 40 years) received a loading dose of oral voriconazole 400 mg twice daily on day 1, followed by voriconazole 200 mg twice daily on days 2 through 9 and voriconazole 200 mg once daily on day 10 with concurrent oral omeprazole 40 mg once daily or matched placebo for 10 days. After a minimum washout period of 7 days, the volunteers were switched over to the opposite treatment arm. Adding omeprazole to the loading dose of voriconazole did not cause a significant change in the Cmax, Tmax, or AUC of voriconazole compared with the addition of placebo. However, at steady-state, the voriconazole Cmax and AUC concentrations were increased by 15% and 41%, respectively. The Tmax was not affected, and the mean Cmin was higher when compared to voriconazole plus placebo; although, none of these pharmacokinetic parameter changes were considered clinically significant. There were 3 volunteers in the study that were poor metabolizers of CYP2C19 and one of these patients had a transient elevation of liver function tests while receiving omeprazole and voriconazole and was withdrawn from the study. Other treatment-related adverse effects included headache, abnormal vision, and photophobia .

B) When omeprazole (40 mg once daily for 7 days) was coadministered with voriconazole (400 mg every 12 hours for 1 day, followed by 200 mg daily for 6 days) in healthy volunteers, the steady-state Cmax and 24-hour AUC of omeprazole were significantly increased by 2 times and 4 times, respectively, compared to omeprazole given without voriconazole .

Omeprazole Overview

• Prescription omeprazole is used alone or with other medications to treat the symptoms of gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and possible injury of the esophagus (the tube between the throat and stomach) in adults and children 1 year of age and older. Prescription omeprazole is used to treat damage from GERD in adults and children 1 month of age and older. Prescription omeprazole is used to allow the esophagus to heal and prevent further damage to the esophagus in adults and children 1 year of age and older with GERD. Prescription omeprazole is also used to treat conditions in which the stomach produces too much acid such as Zollinger-Ellison syndrome in adults. Prescription omeprazole is also used to treat ulcers (sores in the lining of the stomach or intestine) and it is also used with other medications to treat and prevent the return of ulcers caused by a certain type of bacteria (H. pylori) in adults. Nonprescription (over-the-counter) omeprazole is used to treat frequent heartburn (heartburn that occurs at least 2 or more days a week) in adults. Omeprazole is in a class of medications called proton-pump inhibitors. It works by decreasing the amount of acid made in the stomach.

Voriconazole Overview

• Voriconazole is used in adults and children 2 years of age and older to treat serious fungal infections such as invasive aspergillosis (a fungal infection that begins in the lungs and spreads through the bloodstream to other organs), esophageal candidiasis (a yeast [a type of fungus] infection that may cause white patching in the mouth and throat), and candidemia (a fungal infection in the blood). It is also used to treat certain other fungal infections when other medications will not work for certain patients. Voriconazole is in a class of antifungal medications called triazoles. It works by slowing the growth of the fungi that cause infection.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.