What are the contraindications for Diflucan (fluconazole)?

Diflucan (Fluconazole) Contraindications

Fluconazole is contraindicated in patients with hypersensitivity to fluconazole or any of its excipients, and in patients receiving drugs that prolong the QT interval and are metabolized via CYP3A4, specifically erythromycin, pimozide, and quinidine. 1

Absolute Contraindications

Hypersensitivity Reactions

• Patients with documented hypersensitivity to fluconazole or any excipient components must not receive this medication 1
• Cross-hypersensitivity between fluconazole and other azole antifungals is not well-characterized, so caution is warranted in patients with known azole allergies 1
• While rare, hypersensitivity reactions including type 1 reactions have been documented, though desensitization protocols exist for selected cases when no alternatives are available 2

Drug-Drug Interactions with QT-Prolonging Agents

• Coadministration with CYP3A4-metabolized drugs that prolong QT interval is absolutely contraindicated, specifically:
  • Erythromycin 1
  • Pimozide 1
  • Quinidine 1

Relative Contraindications and High-Risk Situations

Cardiac Considerations

• Fluconazole may cause QT interval prolongation, particularly when combined with other QT-prolonging medications including fluoroquinolones, macrolides, ondansetron, and certain chemotherapies like nilotinib and panobinostat 3
• The risk is exacerbated by combination therapy with multiple QT-prolonging agents 3

Specific Clinical Scenarios Requiring Alternative Agents

Decreased cardiac function: Itraconazole (not fluconazole) is contraindicated in patients with decreased ejection fraction or congestive heart failure due to negative inotropic properties 3

Pregnancy: Amphotericin B deoxycholate is the treatment of choice for candidemia in pregnant women, not fluconazole 3

Severe renal dysfunction with IV formulation: While fluconazole itself requires dose adjustment in renal impairment, voriconazole IV (not fluconazole) is contraindicated due to cyclodextrin accumulation 3

Recent azole prophylaxis: Azoles should not be used for treatment in patients who have received azole prophylaxis due to potential resistance 4

Important Drug Interaction Warnings

Cytochrome P450 Enzyme Inhibition

• All azoles including fluconazole inhibit cytochrome P450 enzymes to varying degrees, requiring careful consideration when adding or removing from a patient's regimen 3
• Fluconazole specifically inhibits CYP2C9 and CYP2C19 enzymes with high interpatient variability due to genetic polymorphisms 3
• CYP3A4 inhibition can increase plasma concentrations of co-administered drugs, potentially causing serious adverse events 3

Specific Drug Interactions Requiring Monitoring

• Immunosuppressive medications in transplant patients require careful monitoring 4
• Cyclophosphamide: Itraconazole (not fluconazole specifically) can increase metabolites associated with hyperbilirubinemia and nephrotoxicity 3
• Anticipated interactions with cyclosporin, phenytoin, oral hypoglycemics, and warfarin at higher fluconazole doses 5
• Rifampin decreases fluconazole clearance 5

P-glycoprotein Inhibition

• Itraconazole and posaconazole (not fluconazole specifically) inhibit gastric P-glycoprotein, increasing systemic levels of affected drugs 3

Clinical Pitfalls to Avoid

Do not use fluconazole as initial therapy for patients with suspected endocardial or CNS candidiasis; use fungicidal agents like amphotericin B instead 3

Avoid in moderately-to-severely ill patients with recent azole exposure or high risk of C. glabrata or C. krusei infection; echinocandins are preferred 3

Monitor liver function: While serious hepatotoxicity is rare, liver enzyme elevations can occur and require monitoring 3, 6