Fluconazole with Zidovudine Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Zidovudine
- AZT
- Retrovir®
- ZDV
- Zidovudine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
Increased zidovudine exposure
Interaction Summary
Concomitant use of fluconazole and zidovudine substantially increased zidovudine exposure which may increase the risk for toxicity. Following concomitant administration, zidovudine Cmax increased by 84% and AUC increased by 74% which was likely due to a 45% reduction in zidovudine clearance. If concomitant use is required monitor patients for zidovudine toxicity and consider reducing the zidovudine dosage. Due to its long half-life, the enzyme inhibitory effect of fluconazole may persist for 4 to 5 days following discontinuation.
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Coadministration of fluconazole with zidovudine may increase zidovudine exposure and risk for toxicity. If concomitant use is required, monitor patients for zidovudine toxicity and consider reducing the zidovudine dosage. Due to its long half-life, the enzyme inhibitory effect of fluconazole may persist for 4 to 5 days following discontinuation
Mechanism Of Interaction
Decreased zidovudine clearance
Literature Reports
A) Concomitant use of fluconazole and zidovudine decreased zidovudine clearance by 45% and increased zidovudine exposure. Zidovudine Cmax increased by 84% and AUC increased by 74% and zidovudine t(1/2) was prolonged by approximately 128% .
B) Plasma zidovudine concentrations were determined on two occasions (before and following fluconazole 200 mg daily for 15 days) in 13 volunteers with AIDS or ARC who were on a stable zidovudine dose for at least two weeks. There was a significant increase in zidovudine AUC following the administration of fluconazole. The mean +/- SD increase in AUC was 20% +/- 32% (range: -27 to 104%). The metabolite, GZDV, to parent drug ratio significantly decreased after the administration of fluconazole, from 7.6 +/- 3.6 to 5.7 +/- 2.2 .
C) Twelve HIV-infected men on oral zidovudine therapy (200 mg every eight hours) were randomized to receive concurrent oral fluconazole (400 mg once daily) for seven days or zidovudine alone with a second-phase, crossover trial after a 3-week washout period. The study team reported statistically significant effects on zidovudine pharmacokinetics, including 74% increased area under the serum concentration time curve, 43% decreased oral clearance rates, 48% decreased clearance to zidovudine glucuronide, and 84% increased maximum serum concentrations when concurrent fluconazole was used .
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.
Zidovudine Overview
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Zidovudine is used along with other medications to treat human immunodeficiency virus (HIV) infection. Zidovudine is given to HIV-positive pregnant women to reduce the chance of passing the infection to the baby. Zidovudine is in a class of medications called nucleoside reverse transcriptase inhibitors (NRTIs). It works by decreasing the amount of HIV in the blood. Although zidovudine does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus to other people.
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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:
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.