Fluconazole, often known by its brand name Diflucan, is a widely prescribed azole antifungal medication used to treat various fungal and yeast infections [1.2.6, 1.4.3]. It functions by killing the fungus causing the infection [1.3.2]. While effective, its safety hinges on understanding potential risks and interactions. Before starting treatment, it's critical to discuss your full medical history and all current medications with your healthcare provider [1.4.1].
Critical Drug Interactions to Avoid
Fluconazole can have dangerous interactions with numerous other drugs because it inhibits a key enzyme in the body called CYP3A4, and to a lesser extent, CYP2C9 [1.2.1]. This inhibition can lead to increased blood concentrations of other medications, heightening the risk of serious side effects [1.2.1].
Heart Rhythm Medications
One of the most severe risks is an interaction with drugs that prolong the QT interval on an electrocardiogram (EKG) [1.2.1]. This combination can lead to a life-threatening heart rhythm called torsades de pointes [1.2.5]. Co-administration of fluconazole with drugs like quinidine, pimozide, and erythromycin is contraindicated [1.2.3, 1.2.4]. Other heart medications, certain antibiotics (macrolides, fluoroquinolones), and antipsychotics also pose a risk [1.2.1, 1.2.2].
Statins and Blood Thinners
Taking fluconazole with certain statins used for cholesterol management (like atorvastatin, simvastatin, and lovastatin) can increase statin levels, raising the risk for muscle damage (myopathy) or a severe condition called rhabdomyolysis [1.2.1, 1.2.2]. Similarly, when taken with blood thinners like warfarin (Jantoven), fluconazole can increase the risk of bleeding events by slowing warfarin's metabolism [1.2.3, 1.2.5]. Your doctor will need to monitor you closely and may need to adjust dosages [1.2.3].
Other Notable Interactions
- Immunosuppressants: Drugs like cyclosporine, tacrolimus, and sirolimus can reach toxic levels when combined with fluconazole, potentially leading to kidney damage [1.2.1]. Dose reduction and monitoring are essential [1.2.1].
- Certain Diabetes Drugs: Medications like glyburide and glipizide can have their effects amplified, leading to dangerously low blood sugar (hypoglycemia) [1.2.2, 1.2.5].
- Opioid Pain Relievers: The effects of opioids like fentanyl and methadone can be enhanced, increasing the risk of sedation and respiratory depression [1.2.1, 1.2.2].
- Cannabis and CBD: Fluconazole can slow the clearance of cannabis from the body, potentially increasing its side effects [1.2.2, 1.2.5].
Foods, Drinks, and Activities to Consider
While fluconazole can be taken with or without food, some precautions are advised [1.3.2, 1.8.2].
- Alcohol: Although not strictly contraindicated, combining alcohol and fluconazole should be done with caution and in moderation. Both substances are processed by the liver, and combining them can increase liver strain [1.2.1]. Drinking alcohol may also worsen side effects like dizziness [1.2.2].
- Grapefruit Juice: Grapefruit juice also inhibits the CYP3A4 enzyme [1.2.1]. Consuming it with fluconazole can create an additive effect, further increasing the concentration and potential side effects of other medications that rely on this enzyme for metabolism [1.2.1].
- Caffeine: Fluconazole may slow the body's ability to clear caffeine, potentially increasing side effects like feeling jittery or a fast heartbeat [1.3.1, 1.8.5].
- Driving and Operating Machinery: Fluconazole can cause dizziness or, in rare cases, seizures [1.4.1, 1.4.2]. You should not drive or operate machinery until you know how the medication affects you [1.4.1].
Health Conditions That Require Caution
You should not take fluconazole if you've had a known allergic reaction to it or other azole antifungals [1.2.3, 1.4.1]. Inform your doctor if you have any of the following conditions:
- Liver or Kidney Problems: Fluconazole is primarily cleared by the kidneys and can cause liver toxicity, ranging from mild enzyme elevations to, rarely, severe liver failure [1.6.1, 1.6.3]. Patients with pre-existing liver or kidney disease need careful monitoring, and dosage adjustments may be necessary for those with impaired kidney function [1.6.1, 1.2.2].
- Heart Conditions: If you have a history of irregular heartbeats or Long QT syndrome, your risk of cardiac side effects from fluconazole may be higher [1.4.2].
- Pregnancy and Breastfeeding: Taking high doses of fluconazole during the first trimester may be associated with a rare pattern of birth defects [1.5.6]. It should generally be avoided during pregnancy unless the potential benefit outweighs the risk [1.5.5, 1.5.6]. The drug passes into breast milk, but is generally considered acceptable for use during breastfeeding as the amount is less than a typical neonatal dose [1.5.1, 1.5.3].
Comparison: Fluconazole vs. Other Antifungals
| Feature | Fluconazole | Itraconazole | Miconazole |
|---|---|---|---|
| Administration | Oral tablet or IV [1.7.3] | Oral or IV [1.7.2] | Topical cream or suppository [1.7.1] |
| Prescription Status | Prescription only [1.7.1] | Prescription only | Over-the-counter and prescription [1.7.1] |
| Spectrum | Broad activity against most Candida and Cryptococcus species [1.7.2]. | Similar to fluconazole but also active against Aspergillus [1.7.2]. | Used for topical yeast infections [1.7.1]. |
| Key Interactions | High potential for drug interactions via CYP enzymes [1.2.1, 1.7.3]. | Also a CYP3A4 inhibitor; has a black box warning for patients with heart failure [1.7.2]. | No known drug interactions when used topically [1.7.3]. |
| Common Side Effects | Headache, nausea, abdominal pain [1.4.4]. | Gastrointestinal issues [1.7.5]. | Local irritation, burning [1.7.1]. |
Conclusion
Fluconazole is a potent antifungal, but its use requires careful consideration of your health and other medications. The most critical step is open communication with your doctor and pharmacist. Always provide them with a complete list of your medications—including over-the-counter drugs, vitamins, and supplements—to avoid potentially dangerous interactions [1.4.2]. Do not stop taking the medication early without consulting your doctor, as this could cause the infection to return [1.8.1].
For more detailed information, you can consult the FDA drug label information.
