Fluconazole with Omeprazole Interaction Details

Brand Names Associated with Fluconazole

Brand Names Associated with Omeprazole

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 27, 2023

Interaction Effect

Increased omeprazole exposure

Interaction Summary

Concurrent administration of omeprazole, a CYP2C19 and CYP3A4 substrate, and fluconazole, a combined inhibitor of CYP2C19 and CYP3A4, has been shown to significantly increase omeprazole AUC and Cmax levels, most likely due to the inhibition of omeprazole metabolism by fluconazole . In a separate pharmacokinetic analysis, the pharmacokinetics of fluconazole were not significantly altered with concomitant omeprazole administration . Although omeprazole dosage adjustments are not normally necessary when these agents are coadministered, a dosage adjustment may be considered in patients with Zollinger-Ellison's syndrome when higher omeprazole doses are used (up to 240 mg/day). Additionally, monitor patients for increased omeprazole adverse events (e.g., elevated liver enzymes, headache, diarrhea, abdominal pain) . Fluconazole-mediated enzyme inhibition may persist for 4 to 5 days after discontinuation. If concomitant use is required, carefully monitor for side effects .

Severity

Major

Onset

Rapid

Evidence

Established

How To Manage Interaction

Caution is recommended when omeprazole is coadministered with combined CYP2C19 and CYP3A4 inhibitors such as fluconazole as this may lead to increased omeprazole plasma levels. Dosage adjustment of omeprazole is not routinely necessary when these agents are used concomitantly, but may be considered in patients with Zollinger-Ellison's syndrome when higher omeprazole doses are used (up to 240 mg/day). Fluconazole-mediated enzyme inhibition may persist for 4 to 5 days after discontinuation. If concomitant use is required, carefully monitor for side effects .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated omeprazole metabolism by fluconazole; inhibition of CYP2C19-mediated omeprazole metabolism by fluconazole

Literature Reports

A) Coadministration of omeprazole with fluconazole increased omeprazole Cmax and AUC concentrations by 2.4 and 6.3 times, respectively, compared with omeprazole administration alone in a pharmacokinetic study in healthy male volunteers. On day 1, subjects (n=18; mean age, 25 years) received a single oral dose of omeprazole 20 mg. Following a 10-day washout period, oral fluconazole 100 mg once daily was given on days 12 through 16. On day 16, subjects were coadministered omeprazole 20 mg with fluconazole 100 mg. Coadministration of omeprazole with fluconazole resulted in an omeprazole AUC increase from 491 to 3090 nanogram (ng) x hr/mL and a Cmax increase from 311 to 746 ng/mL (900 to 2160 nanomol/L) compared with administration of omeprazole alone. The half-life of omeprazole increased from 0.85 to 2.59 hours with coadministration of fluconazole. No adverse events were observed during the study . In a separate pharmacokinetic study (n=12) assessing the influence of gastric pH on fluconazole, omeprazole treatment demonstrated no significant effect on the pharmacokinetics of fluconazole .

Fluconazole Overview

• Fluconazole is used to treat fungal infections, including yeast infections of the vagina, mouth, throat, esophagus (tube leading from the mouth to the stomach), abdomen (area between the chest and waist), lungs, blood, and other organs. Fluconazole is also used to treat meningitis (infection of the membranes covering the brain and spine) caused by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected because they are being treated with chemotherapy or radiation therapy before a bone marrow transplant (replacement of unhealthy spongy tissue inside the bones with healthy tissue). Fluconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.

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.

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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.