Drug Interaction Management: Fluconazole and Acalabrutinib
Wait at least 5-7 days after a single 400mg fluconazole dose before initiating acalabrutinib to allow adequate clearance of fluconazole and minimize the risk of severe drug interactions.
Rationale Based on Fluconazole Pharmacokinetics
The timing recommendation is based on fluconazole's elimination characteristics:
- Fluconazole has a long elimination half-life of approximately 30-31 hours in patients with normal renal function 1, 2, 3
- After a single dose, it takes approximately 5-7 half-lives (150-217 hours, or roughly 6-9 days) for the drug to be essentially eliminated from the body 2, 3
- Steady-state requires a minimum of 6 days to achieve, indicating the drug's prolonged presence in the system 2
Clinical Considerations for Timing
Standard Approach (Normal Renal Function)
- Wait 7 days after the 400mg fluconazole dose before starting acalabrutinib to ensure >95% elimination 2, 3
- This allows approximately 5.5 half-lives to pass, reducing fluconazole plasma concentrations to negligible levels
Renal Impairment Considerations
- In patients with renal insufficiency, the fluconazole half-life is significantly prolonged, requiring longer waiting periods 2
- Approximately 80% of fluconazole is eliminated unchanged in the urine, making renal function the primary determinant of clearance 3
- For patients with creatinine clearance <50 mL/min, consider waiting 10-14 days before initiating acalabrutinib
Critical Illness Considerations
- Critically ill patients may have altered pharmacokinetics that could affect fluconazole clearance 4, 5
- In patients receiving continuous renal replacement therapy, fluconazole clearance is enhanced, potentially allowing shorter waiting periods 4, 5
Monitoring Recommendations
While waiting to initiate acalabrutinib:
- Assess renal function (creatinine clearance) to determine if standard timing applies 2
- Evaluate for any signs of ongoing fungal infection that might require continued antifungal therapy 6
- Consider the urgency of acalabrutinib initiation for the underlying hematologic malignancy
Alternative Strategies if Earlier Initiation Required
If clinical circumstances demand earlier acalabrutinib initiation:
- Consult with both oncology and infectious disease specialists to weigh the risks of drug interaction against treatment delay
- Consider therapeutic drug monitoring if available to confirm fluconazole clearance
- Implement enhanced monitoring for acalabrutinib-related toxicities including bleeding and infection