Europe’s Pharmacovigilance Risk Assessment Committee (PRAC) has issued a new safety warning about the management of renal dialysis in critically ill patients receiving the antifungal agent caspofungin. The committee endorsed a direct healthcare professional communication that will alert practitioners to possible hazards from the use of polyacrylonitrile-based membranes during continuous renal replacement therapy in these patients. 

Caspofungin is an echinocandin, a class of lipopeptide antifungal agents that noncompetitively inhibit an enzyme needed to synthesize a crucial component of the fungal cell wall, leading to osmotic instability and eventually cell lysis. The drug is given by intravenous infusion for the treatment of fungal infections in adults and children, and is indicated in Europe for:

• Treatment of invasive candidiasis
• Treatment of invasive aspergillosis in patients refractory to or intolerant of lipid formulations of amphotericin B and/or itraconazole, with refractoriness defined as progression of infection or failure to improve after a minimum of 7 days of prior therapeutic doses of effective antifungal therapy
• Empiric therapy for presumed fungal infections (such as Candida or Aspergillus) in febrile or neutropenic patients

Candidiasis Common in ICU Patients

Candida infections are a common cause of nosocomial bloodstream infections in critically ill patients and are associated with significant mortality. Critically ill patients in the ICU frequently undergo continuous renal replacement therapy for acute kidney injury and fluid overload. This involves nonstop dialysis that may be life-saving. 

However, polyacrylonitrile membranes, used to filter blood during dialysis, can bind caspofungin and decrease its effectiveness, PRAC warned. Lack of caspofungin effectiveness has been reported in patients undergoing dialysis with these membranes.

Caspofungin Sequestration by Dialysis Membrane

A multicenter in vitro study in France, published in the International Journal of Antimicrobial Agents in 2023, demonstrated caspofungin sequestration in a polyacrylonitrile-derived filter. Reduced drug concentrations were not mitigated by increasing the dose of caspofungin. The authors advised professionals to exercise caution about the simultaneous use of caspofungin and polyacrylonitrile-derived filters. Intermittent modes of renal replacement therapy might be considered, they suggested, or, for sensitive species, fluconazole might be an alternative drug.

However, more recently an in vivo study (also in France), published in Infectious Diseases and Therapy in August 2025, found no evidence of caspofungin depletion in a retrospective study of 35 ICU patients undergoing continuous dialysis with polyacrylonitrile-based membranes. The researchers suggested that further research on clinical outcomes is warranted.

Consider Alternatives

PRAC said that antifungal treatment failure may lead to worsening of the systemic fungal infection, which may be fatal in critically ill patients on dialysis. Healthcare professionals should verify the type of hemofiltration membrane used before initiating and during treatment with caspofungin. If polyacrylonitrile-derived membranes are involved, healthcare professionals should either switch to an alternative membrane or consider an alternative antifungal medicine.