What are the side effects of Diflucan (fluconazole)?

Side Effects of Diflucan (Fluconazole)

Fluconazole commonly causes headache (13%), nausea (7%), abdominal pain (6%), diarrhea (3%), dizziness (1%), and taste disturbances (1%), with more serious adverse effects including hepatotoxicity, QT prolongation, and allergic reactions requiring careful monitoring in at-risk patients. 1

Common Side Effects

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

Gastrointestinal Effects

• Nausea (3.7%)
• Vomiting (1.7%)
• Abdominal pain (1.7%)
• Diarrhea (1.5%)
• Dyspepsia (1%) 1

Neurological Effects

• Headache (1.9-13%, depending on indication)
• Dizziness (1%)
• Taste perversion (1%) 1

Dermatological Effects

• Skin rash (1.8%)
• Xerosis (dry skin) (16.9% with long-term use)
• Alopecia (16.1% with long-term use) 1, 2

Serious Adverse Effects

Hepatotoxicity

• Transient elevations in liver enzymes are common
• Serious hepatic reactions including clinical hepatitis, cholestasis, and fulminant hepatic failure have been reported, though rare
• Risk factors include AIDS, malignancy, and concomitant hepatotoxic medications
• Baseline and periodic liver function tests are recommended, especially for prolonged courses 1, 3

Cardiovascular Effects

• QT prolongation
• Torsade de pointes (rare but serious) 1

Allergic Reactions

• Anaphylaxis (including angioedema, face edema, and pruritus) in rare cases
• Serious skin reactions that can be life-threatening have been reported in patients with serious medical conditions 1

Endocrine Effects

• Adrenal insufficiency (reversible) with symptoms including:
  • Fatigue
  • Muscle weakness
  • Loss of appetite
  • Weight loss
  • Stomach pain
  • Dizziness
  • Nausea/vomiting 1

Long-Term Use Considerations

With prolonged therapy (such as for coccidioidomycosis), additional side effects may emerge:

• 51.6% of patients on long-term therapy experience adverse effects
• 65.6% of those experiencing adverse effects require therapeutic intervention (dose reduction, discontinuation, or switch to alternative agent)
• Higher daily doses (mg/kg) correlate with increased adverse effects 2

Drug Interactions

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

• Increased anticoagulant effect with warfarin
• Enhanced hypoglycemic effects with oral hypoglycemics
• Increased risk of myopathy and rhabdomyolysis with statins
• Increased oxycodone plasma concentrations (potential respiratory depression)
• Complex interactions with HIV medications (protease inhibitors and non-nucleoside reverse transcriptase inhibitors) 3

Special Populations

Renal Impairment

• Dosage adjustment required due to primarily renal elimination
• Increased risk of toxicity without appropriate dose reduction 3

Hepatic Disease

• Increased risk of hepatotoxicity
• Careful monitoring recommended 1

Elderly

• More susceptible to adverse effects due to age-related changes in drug metabolism 3

Pregnancy

• Single-dose treatment in first trimester has not been associated with increased anomalies
• Prolonged use at high doses in first trimester has been associated with craniofacial and skeletal defects 3

Monitoring Recommendations

1. Before starting fluconazole:

   • Review complete medication list for potential interactions
   • Perform baseline liver function tests

2. During therapy:

   • Monitor for signs of liver injury
   • Watch for allergic reactions
   • Monitor for interactions with other medications
   • Adjust doses of affected medications as needed

3. After discontinuing:

   • Continue monitoring for interactions during the 4-5 day period after discontinuation
   • Readjust doses of interacting medications as the fluconazole effect wanes 3, 1

The risk of side effects must be weighed against the benefits of treatment, particularly for long-term therapy or in patients with underlying medical conditions.