Posaconazole Dosing in Chronic Kidney Disease
No dosage adjustment of posaconazole is required for patients with chronic kidney disease, including those with severe renal impairment. 1
Pharmacokinetic Considerations in CKD
Posaconazole's pharmacokinetics are not significantly affected by renal impairment, making it a suitable antifungal option for patients with CKD:
According to the FDA label, following single-dose administration of 400 mg posaconazole, there was no significant effect of mild (eGFR: 50-80 mL/min/1.73 m²) or moderate (eGFR: 20-49 mL/min/1.73 m²) renal impairment on posaconazole pharmacokinetics 1
In patients with severe renal impairment (eGFR <20 mL/min/1.73 m²), the mean plasma exposure (AUC) was similar to that in patients with normal renal function 1
Clinical studies have demonstrated no correlation between posaconazole pharmacokinetics and mild to moderate renal disease 2
Dosing Recommendations
For patients with CKD requiring posaconazole:
- Standard dosing should be maintained regardless of renal function
- For fluconazole-refractory disease, posaconazole suspension 400 mg twice daily for 3 days followed by 400 mg daily for up to 28 days is recommended 3
- For prophylaxis or treatment of invasive fungal infections, follow standard dosing protocols
Monitoring Considerations
While dosage adjustment is not required, additional monitoring is recommended:
Patients with severe renal impairment should be monitored closely for breakthrough fungal infections due to the higher variability in drug exposure (CV=96%) compared to patients with better renal function (CV<40%) 1
Monitor for potential drug interactions, as posaconazole inhibits cytochrome P450 enzymes and may interact with other medications commonly used in CKD patients 4
Regular assessment of liver function is advisable, as rare cases of hepatotoxicity have been reported 1
Special Considerations
Hemodialysis: Posaconazole is not removed by hemodialysis, so supplemental dosing after dialysis is not required 1, 2
Protein binding: Posaconazole is approximately 98% protein-bound, which is unaffected by renal impairment or hemodialysis 2
Safety profile: Clinical studies have shown that posaconazole is generally well tolerated in patients with renal impairment, with adverse event profiles similar to those with normal renal function 5
Potential Adverse Effects to Monitor
While generally well-tolerated in CKD patients, monitor for:
- Gastrointestinal effects (nausea, vomiting, abdominal pain)
- Altered levels of concomitant medications
- Rare cases of acute kidney injury have been reported (0.1-1% of patients) 6
Conclusion
Posaconazole offers a significant advantage for CKD patients requiring antifungal therapy, as it does not require dose adjustment even in severe renal impairment. This contrasts with other antifungals that may require significant dose modifications in renal disease. Close monitoring for breakthrough infections is still recommended in patients with severe renal impairment due to the higher variability in drug exposure.