What medications are contraindicated with Diflucan (fluconazole)?

Medications Contraindicated with Diflucan (Fluconazole)

Diflucan (fluconazole) should not be taken with medications that prolong the QT interval and are metabolized via CYP3A4, including pimozide, quinidine, and erythromycin, as this combination can lead to life-threatening cardiac arrhythmias.

Major Contraindications and Drug Interactions

Absolutely Contraindicated Medications

• QT-prolonging medications metabolized by CYP3A4:
  • Pimozide
  • Quinidine
  • Erythromycin 1

Severe Drug Interactions (Use with Extreme Caution)

1. Anticoagulants:

   • Warfarin: Fluconazole significantly increases prothrombin time and bleeding risk 1, 2

2. Antiepileptics:

   • Phenytoin: Fluconazole increases phenytoin AUC by 88% (range: 16-247%) 1
   • Carbamazepine: Fluconazole increases serum carbamazepine by approximately 30% 1

3. Oral Hypoglycemics:

   • Tolbutamide: AUC increased by 26% 1
   • Glipizide: AUC increased by 49% 1
   • Glyburide: AUC increased by 44% 1

4. Immunosuppressants:

   • Cyclosporine: AUC increased by 92% 1
   • Tacrolimus: Significantly increased serum levels 1

5. Benzodiazepines:

   • Midazolam: Clearance reduced by 51%, AUC increased by 259% 1

6. HIV Medications:

   • Nevirapine: Should not be given with rifamycins 3
   • Rilpivirine: Should not be given with rifamycins 3

7. Rifamycins:

   • Rifabutin: Fluconazole increases serum levels of rifabutin 1
   • Rifampin: Decreases fluconazole half-life and effectiveness 4

8. Calcium Channel Blockers:

   • Nifedipine, isradipine, amlodipine, verapamil, felodipine: Fluconazole increases systemic exposure 1

9. Anti-inflammatory Drugs:

   • Celecoxib: AUC increased by 134% 1

10. HCV Medications:

    • Simeprevir: Contraindicated with fluconazole 3

Mechanism of Interactions

Fluconazole is:

• A moderate inhibitor of CYP2C9 and CYP3A4
• A strong inhibitor of CYP2C19 1

These enzyme inhibiting effects persist 4-5 days after discontinuation due to fluconazole's long half-life (31-37 hours) 1, 5.

Special Considerations

Cardiac Risk

• Fluconazole causes QT prolongation via inhibition of Rectifier Potassium Channel current (Ikr)
• QT prolongation caused by other medications may be amplified via CYP3A4 inhibition 1
• Patients with hypokalemia and advanced cardiac failure are at increased risk for life-threatening ventricular arrhythmias and torsade de pointes 1, 6

Renal Impairment

• Fluconazole is primarily eliminated unchanged in urine (60% of dose)
• Dosage adjustment required in renal impairment 1, 5

Common Pitfalls to Avoid

1. Failing to recognize delayed interactions: The enzyme inhibiting effect of fluconazole persists 4-5 days after discontinuation 1

2. Overlooking non-prescription medications: Some herbal supplements like St. John's wort can interact with fluconazole 3

3. Missing the cumulative effect: Multiple medications with similar side effects (e.g., QT prolongation) can have additive effects when combined with fluconazole

4. Ignoring patient-specific factors: Elderly patients, those with electrolyte abnormalities, or renal impairment may experience more severe interactions 1

Remember to review all medications, including over-the-counter drugs and supplements, before prescribing or taking fluconazole to avoid potentially dangerous drug interactions.