Can fluconazole (antifungal medication) cause thrombocytopenia (low platelet count)?

Fluconazole and Thrombocytopenia

Yes, fluconazole can cause thrombocytopenia, though this is a rare adverse effect. The hematologic toxicity is well-documented in case reports and pharmacovigilance data, but occurs infrequently enough that it does not typically limit clinical use.

Evidence for Hematologic Toxicity

Fluconazole-associated thrombocytopenia is documented but uncommon, with rapid reversal upon drug discontinuation. 1

• A case report demonstrated agranulocytosis with thrombocytopenia developing within 48 hours of fluconazole administration, with recovery beginning within 48 hours of discontinuation 1
• The Naranjo algorithm assessment in this case yielded a "probable" causality score of 6 points, indicating strong evidence for drug-induced blood dyscrasia 1
• Another case documented thrombocytopenia requiring fluconazole discontinuation during long-term suppressive therapy for cryptococcal meningitis in an AIDS patient, with resolution after stopping the drug 2

Incidence and Clinical Significance

Population-based surveillance data confirms that serious hematologic adverse events with fluconazole are extremely rare, occurring at approximately 2.8 per 100,000 prescriptions. 3

• A large UK General Practice Research Database study of 54,803 fluconazole and itraconazole users identified only one case of thrombocytopenia and one case of neutropenia attributable to fluconazole 3
• The rate of serious adverse blood events was 2.8/100,000 prescriptions (95% CI 0.8-10.3) 3
• The Centers for Disease Control and Prevention notes that hematologic effects including thrombocytopenia and leukopenia are rare with fluconazole, being more commonly associated with itraconazole 4

Clinical Monitoring Recommendations

When prescribing fluconazole, particularly for prolonged therapy, baseline and periodic monitoring of complete blood counts is prudent, though not universally mandated by guidelines. 4

• Monitor liver function with baseline and periodic assessments (at 2 weeks, 4 weeks, then every 3 months) during prolonged fluconazole therapy 4
• Be vigilant for temporal relationships between fluconazole initiation and new-onset cytopenias 1
• Consider fluconazole as a potential cause when unexplained thrombocytopenia develops in patients receiving the medication 1, 2

Important Caveats

Drug interactions may potentiate hematologic toxicity through altered metabolism. 5

• Fluconazole inhibits cytochrome P450 enzymes (CYP2C9, CYP2C19, CYP3A4), which can affect metabolism of other medications and potentially contribute to adverse effects 4, 6
• In one case, fluconazole combined with ciprofloxacin inhibited metabolism of avatrombopag, contributing to severe metabolic complications in a patient with thrombocytopenia 5
• Higher doses of fluconazole (≥200 mg/day) pose greater risk for drug interactions due to more potent enzyme inhibition 6

Clinical Context

Despite this rare association, fluconazole remains widely recommended across multiple guidelines for antifungal prophylaxis and treatment in high-risk populations, including neutropenic patients, transplant recipients, and critically ill patients 7. The benefit-risk profile remains favorable for appropriate indications, with thrombocytopenia representing an uncommon but reversible adverse effect requiring awareness rather than avoidance of the drug.