What are the side effects of fluconazole?

Side Effects of Fluconazole

Fluconazole commonly causes headache, nausea, abdominal pain, diarrhea, and dizziness, with more serious adverse effects including hepatotoxicity, QT prolongation, and allergic reactions occurring less frequently. 1

Common Side Effects

Fluconazole is generally well tolerated, but several side effects may occur:

• Most common side effects (1-5% of patients):
  • Headache (13% in single-dose therapy for vaginal candidiasis)
  • Nausea (7% in single-dose therapy)
  • Abdominal pain (6% in single-dose therapy)
  • Diarrhea (3% in single-dose therapy, 1.5% in multi-dose therapy)
  • Dizziness (1%)
  • Taste perversion (1%)
  • Vomiting (1.7% in multi-dose therapy)
  • Skin rash (1.8% in multi-dose therapy) 1

Serious Adverse Effects

Hepatobiliary Effects

• Hepatotoxicity: Rare but serious hepatic reactions ranging from mild transaminase elevations to fulminant hepatic failure and death
• Risk factors for hepatotoxicity include:
  • AIDS or malignancy
  • Concomitant hepatotoxic medications
  • Multiple medications 1

Cardiovascular Effects

• QT prolongation and torsade de pointes (rare but potentially fatal) 1
• Avoid in patients with pre-existing cardiac conditions or those taking other QT-prolonging medications 2

Immunologic/Dermatologic Reactions

• Serious allergic reactions including anaphylaxis, angioedema, face edema, and pruritus (rare)
• Serious skin reactions that can be life-threatening in patients with serious underlying conditions 1

Endocrine Effects

• Adrenal insufficiency (reversible): Presents with fatigue, muscle weakness, loss of appetite, weight loss, stomach pain, dizziness, nausea, and vomiting 1

Long-Term Therapy Side Effects

With prolonged use (particularly relevant for antifungal prophylaxis or treatment of systemic mycoses):

• Xerosis (dry skin) (16.9%)
• Alopecia (hair loss) (16.1%)
• Fatigue (11.3%)
• Approximately 65.6% of patients on long-term therapy may require dose reduction, discontinuation, or switch to another antifungal due to adverse effects 3

Drug Interactions

Fluconazole has substantial drug interactions due to inhibition of cytochrome P450 enzymes:

• Warfarin: Increased anticoagulant effect requiring dose adjustment
• Oral hypoglycemics: Enhanced hypoglycemic effects
• Phenytoin: Increased phenytoin levels and toxicity
• Cyclosporine: Increased immunosuppressant levels
• Rifampin: May decrease fluconazole levels
• Statins: Increased risk of myopathy and rhabdomyolysis
• Opioids: Significantly increases oxycodone plasma concentrations 2, 1

Special Populations

Pregnancy

• Fluconazole is teratogenic at high doses in animal studies
• Cases of craniofacial and skeletal defects have been reported after prolonged use at high doses in the first trimester
• Single-dose treatment in the first trimester has not been associated with increased anomalies 4

Renal Impairment

• Dosage adjustment required due to primarily renal elimination
• Increased risk of toxicity without appropriate dose reduction 1

Elderly

• More susceptible to adverse effects due to age-related changes in drug metabolism 2

Monitoring Recommendations

• Baseline liver function tests before initiating therapy
• Periodic monitoring of liver function during treatment, especially for prolonged courses
• Discontinue fluconazole if signs of liver injury develop (jaundice, dark urine, light-colored stools, severe itching, fatigue, loss of appetite)
• Monitor for drug interactions when starting or stopping fluconazole, as effects may persist for 4-5 days after discontinuation 2, 1

Fluconazole's side effect profile should be carefully considered when selecting antifungal therapy, particularly for patients with underlying liver disease, cardiac conditions, or those taking multiple medications with potential interactions.