Key takeaways:
Fluconazole (Diflucan) is a prescription medication that treats different types of fungal infections, including yeast infections.
Fluconazole can interact with medications that affect your heart rhythm, which may raise your risk of developing arrhythmias. It can also interact with warfarin, certain statins, and some antidepressants.
Before starting fluconazole, talk to your prescriber or pharmacist to see if your medications or supplements may interact with it.
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Fluconazole (Diflucan) is a popular antifungal medication. It treats various infections caused by fungi, such as vaginal yeast infections, oral thrush, and more. Fluconazole is often prescribed as an oral tablet, but it also comes as a liquid suspension and IV injection.
Fluconazole can interact with other medications because of how it affects certain liver enzymes (proteins). These interactions can change how fluconazole or other medications work in your body. Some interactions may reduce medication effectiveness, while others could lead to added side effects.
Before starting your course of fluconazole, your prescriber and pharmacist will likely want to check for potential drug interactions. Make sure to give them a list of your current medications, including any over-the-counter (OTC) products, vitamins, or supplements you take.
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Fluconazole interaction summary
These medications are most known for interacting with fluconazole:
Amiodarone (Pacerone)
Anticoagulants, such as warfarin (Coumadin, Jantoven)
Antiplatelets, such as clopidogrel (Plavix)
Anti-seizure medications, such as phenytoin (Dilantin, Phenytek)
Calcium channel blockers, such as amlodipine (Norvasc, Norliqva)
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin)
Sulfonylureas, such as glyburide (DiaBeta, Glynase)
Statins, such as atorvastatin (Atorvaliq, Lipitor)
Lemborexant (Dayvigo)
Losartan (Cozaar)
Organ transplant medications, such as tacrolimus (Prograf)
Certain selective serotonin reuptake inhibitors (SSRIs), such as citalopram (Celexa)
Tricyclic antidepressants, such as amitriptyline
Benzodiazepines, such as alprazolam (Xanax)
Some opioids, such as methadone (Methadose)
Vinca alkaloids, such as vincristine
Some kinase inhibitors, such as tofacitinib (Xeljanz)
Other antifungals, such as voriconazole (Vfend)
Keep reading to learn more about six notable fluconazole interactions, which we discuss in detail below.
Keep in mind: This isn’t a complete list of medications that fluconazole can interact with. Make sure to check in with a healthcare professional when you start or stop a new medication or supplement while taking fluconazole.
1. Warfarin
Warfarin is a blood thinner that treats and prevents blood clots. It also helps prevent certain complications from occurring in people with heart conditions, such as strokes in those who have atrial fibrillation.
After you take warfarin, it gets broken down by two specific enzymes in the body. Fluconazole stops these enzymes from working efficiently. So, if you take warfarin and fluconazole at the same time, your INR can go up. This means your blood becomes too thin and takes longer to clot. This may cause you to bruise or bleed easily and can be dangerous if not managed appropriately.
If you take warfarin, you may still be able to take fluconazole. But your healthcare professional may want to lower your warfarin dose while you’re taking fluconazole. They may also check your INR more often while taking both medications.
2. Amiodarone
Amiodarone treats abnormal heart rhythms. Both amiodarone and fluconazole can affect the heart’s electrical activity. Taking them together can raise the risk of developing abnormal heart rhythms. Fluconazole can also cause amiodarone to build up in the body, further increasing the risk of side effects.
Your prescriber may recommend a different antifungal medication. If you need to take amiodarone and fluconazole together, they may monitor your heart rhythm more closely. They may also check and correct your potassium and magnesium levels, since low levels can increase the risk of dangerous heart rhythm problems.
3. Clopidogrel
Clopidogrel is a common antiplatelet medication. It’s prescribed to certain people to lower the risk of heart attack and stroke by stopping blood clots.
Clopidogrel doesn’t start working right away, though. It only works after an enzyme in your body turns it on. Fluconazole can stop this enzyme from working, preventing clopidogrel from working. This worsens the risk of experiencing heart-related problems.
If you take clopidogrel and receive a prescription for fluconazole, talk with your healthcare professional. They may prescribe a different antifungal to be safe.
4. Phenytoin
Phenytoin is a medication that helps prevent seizures in people living with epilepsy. Fluconazole can slow the liver enzymes that break down phenytoin. This may cause phenytoin levels to rise, increasing the risk of side effects.
Symptoms of high phenytoin levels can include:
Drowsiness
Dizziness
Slurred speech
Confusion
Coordination problems
Low blood pressure
Heart rhythm changes
If you take these medications together, your prescriber may check your phenytoin blood levels more often. They may also lower your phenytoin dosage if needed.
5. Statins, such as atorvastatin
Atorvastatin and simvastatin (Zocor, FloLipid) are statins that treat high cholesterol. Fluconazole can slow the liver enzyme that breaks them down, raising their levels in the body. This can increase the risk of statin side effects, particularly muscle pain. In rare cases, it can lead to rhabdomyolysis, a condition in which damaged muscle tissue releases harmful substances into the bloodstream.
If you take atorvastatin or simvastatin, tell your prescriber before starting fluconazole. They may lower your statin dose, temporarily pause it, or switch you to a statin that’s less likely to interact. Contact your healthcare team right away if you develop symptoms such as muscle pain, weakness, and tea-colored urine.
6. Citalopram
Citalopram is an antidepressant medication that makes more serotonin available in the brain. Fluconazole can slow the liver enzymes that break down citalopram. This can raise citalopram levels and increase the risk of side effects.
One possible concern is serotonin syndrome, a rare but potentially serious condition caused by too much serotonin. Tell your prescriber right away if you develop symptoms such as sweating, shaking, and a fast heartbeat. Seek emergency care for severe symptoms such as high fever, confusion, or loss of consciousness.
Citalopram and fluconazole can also affect the heart’s electrical activity. Taking them together may raise the risk of a serious heart rhythm abnormality, especially if you have an existing heart condition.
If you need to take both medications, your prescriber may limit your citalopram dosage to 20 mg once daily. They may also monitor your heart rhythm or recommend a different antifungal medication.
Can you take fluconazole with over-the-counter yeast infection treatments?
No, combining fluconazole with OTC yeast infection treatments isn’t recommended. Fluconazole works throughout your body, while most OTC treatments are applied topically. Using both simultaneously could increase the risk of side effects without making the overall treatment more effective.
Always check with your healthcare professional before using any other medications, including OTC ones, while taking fluconazole.
Are there any foods to avoid while taking fluconazole?
There aren’t any specific foods to avoid while taking fluconazole. You can take it with or without food. However, fluconazole can cause nausea and stomach pain for some people. So taking it with food may help reduce these side effects. It’s also best to avoid alcohol while taking fluconazole. It may increase the risk of liver-related side effects.
Can you take amoxicillin and fluconazole together?
Yes, you can generally take amoxicillin and fluconazole together. There isn’t a known interaction between them, and they may sometimes be prescribed at the same time. Amoxicillin treats bacterial infections, while fluconazole treats certain fungal infections.
The bottom line
Fluconazole (Diflucan) is an antifungal medication that can interact with warfarin (Coumadin, Jantoven), amiodarone (Pacerone), and clopidogrel (Plavix), among others. Some fluconazole interactions increase the risk of side effects of other medications, such as easy bleeding or heart rhythm problems. Others can affect how well other medications work in your body.
Before starting fluconazole, it’s recommended to talk to a healthcare professional about other medications you take, including any over-the-counter medications, herbal products, and supplements. They can check for potential interactions and advise if you need to make any changes to your medication regimen.
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References
Drew, B. J., et al. (2010). Prevention of Torsade de Pointes in hospital settings. Circulation.
Govindarajan, A., et al. (2024). Fluconazole. StatPearls.
Gupta, M., et al. (2023). Phenytoin. StatPearls.
Roerig. (2026). Diflucan- fluconazole tablet; Diflucan- fluconazole powder, for suspension [package insert]. DailyMed.
