From the FDA Drug Label
In post-marketing experience, as with other azole antifungals, bleeding events (bruising, epistaxis, gastrointestinal bleeding, hematuria, and melena) have been reported in association with increases in prothrombin time in patients receiving fluconazole concurrently with warfarin
Yes, fluconazole can cause gastrointestinal (GI) bleed, as evidenced by reports of gastrointestinal bleeding in patients receiving fluconazole, particularly when coadministered with warfarin 1.
From the Research
Fluconazole is not typically associated with causing gastrointestinal bleeding as a direct side effect, but it can interact with other medications that might increase bleeding risk. While fluconazole can cause gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea, GI bleeding is not a commonly reported adverse effect of this medication. Fluconazole works by inhibiting fungal cytochrome P450 enzymes, specifically 14-alpha-demethylase, which disrupts ergosterol synthesis in fungal cell membranes 2. This mechanism of action does not directly affect the integrity of the gastrointestinal mucosa in a way that would typically lead to bleeding. However, it's essential to consider that fluconazole can interact with other medications, such as warfarin and other anticoagulants, by inhibiting their metabolism through the CYP450 enzyme system, potentially increasing the risk of bleeding 3, 4. A recent study found no significant increase in bleeding risk when fluconazole is administered concomitantly with direct oral anticoagulants (DOACs) after controlling for confounding variables 4. If a patient taking fluconazole experiences signs of GI bleeding (such as black tarry stools, bright red blood in vomit or stool, or coffee-ground emesis), they should seek immediate medical attention, as the bleeding is likely due to another cause or a drug interaction rather than fluconazole itself. It is also worth noting that there have been rare reports of fluconazole-associated gastrointestinal bleeding, as seen in a case report where a patient developed lower gastrointestinal system bleeding after taking fluconazole without a prescription 5. In general, the risk of GI bleeding associated with fluconazole is considered low, and the medication is generally well-tolerated 2. Overall, fluconazole is not typically a cause of gastrointestinal bleeding, but caution should be exercised when co-administering it with other medications that may increase bleeding risk.