Fluconazole with Sildenafil Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Sildenafil
- Revatio®
- Sildenafil
- Viagra®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
Increased sildenafil exposure and an increased risk for sildenafil toxicity
Interaction Summary
Concomitant use of a CYP3A4 substrate (such as sildenafil) with fluconazole (a moderate CYP3A4 inhibitor) may increase sildenafil exposure and increase the risk for toxicity. Caution and careful monitoring is advised when using this type of combination of drugs. Fluconazole-mediated enzyme inhibition may persist for 4 to 5 days after discontinuation. Additionally, fluconazole is a potent CYP2C9 inhibitor, and sildenafil is a CYP2C9 substrate. Although a minor pathway, fluconazole-mediated CYP2C9 inhibition may increase sildenafil exposure. If concomitant use of sildenafil and fluconazole is required, consider sildenafil dose reductions: in patients who take sildenafil for erectile dysfunction, use a lower sildenafil starting dose of 25 mg and the maximum single dose in 48 hours should not exceed 25 mg .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant use of a CYP3A4 substrate (such as sildenafil) with fluconazole (a moderate CYP3A4 inhibitor) may increase sildenafil exposure and increase the risk for toxicity. Caution and careful monitoring is advised when using this type of combination of drugs. Fluconazole-mediated enzyme inhibition may persist for 4 to 5 days after discontinuation. Additionally, fluconazole is a potent CYP2C9 inhibitor, and sildenafil is a CYP2C9 substrate. Although a minor pathway, fluconazole-mediated CYP2C9 inhibition may increase sildenafil exposure. If concomitant use of sildenafil and fluconazole is required, consider sildenafil dose reductions: in patients who take sildenafil for erectile dysfunction the maximum single dose in 48 hours should not exceed 25 mg .
Mechanism Of Interaction
Inhibition of CYP3A4-mediated sildenafil metabolism; inhibition of CYP2C9-mediated sildenafil metabolism
Literature Reports
A) Concomitant use of sildenafil with the strong CYP3A4 inhibitor, ritonavir, increased sildenafil AUC by 11-fold. Similarly, coadministration of sildenafil with the strong CYP3A4 inhibitor saquinavir increased sildenafil Cmax 140% and AUC 210%. CYP3A4 inhibitors stronger than saquinavir, such as ketoconazole or itraconazole, are expected to cause similar and greater effects on sildenafil exposure. Concomitant use of sildenafil with the moderate CYP3A4 inhibitor, erythromycin, increased sildenafil Cmax and AUC 160% and 182%, respectively .
Fluconazole Overview
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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.
Sildenafil Overview
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Sildenafil (Viagra) is used to treat erectile dysfunction (impotence; inability to get or keep an erection) in men. Sildenafil (Revatio) is used to improve the ability to exercise in adults and children 1 year of age and older with pulmonary arterial hypertension (PAH; high blood pressure in the vessels carrying blood to the lungs, causing shortness of breath, dizziness, and tiredness). Sildenafil is in a class of medications called phosphodiesterase (PDE) inhibitors. Sildenafil treats erectile dysfunction by increasing blood flow to the penis during sexual stimulation. This increased blood flow can cause an erection. Sildenafil treats PAH by relaxing the blood vessels in the lungs to allow blood to flow easily.
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If you are taking sildenafil to treat erectile dysfunction, you should know that it does not cure erectile dysfunction or increase sexual desire. Sildenafil does not prevent pregnancy or the spread of sexually transmitted diseases such as human immunodeficiency virus (HIV).
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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.