Table 1.

Summary of clinical interactions between high-dose cyclophosphamide and antifungal agents in patients undergoing HSCT

Antifungal agent	Mechanism of interaction	Severity	Outcome	Documentation	Ref.
Fluconazole	Strong inhibition of CYP2C19-mediated activation of Cy Moderate inhibition of CYP2C9-mediated activation of Cy Moderate inhibition of CYP3A4-mediated activation and detoxification of Cy	Moderate	↕Toxicity	Suspected	[4, 5]
Itraconazole	Strong Inhibition of CYP3A4-mediated activation of Cy Synergist cardiotoxicity effects	Moderate	↑↑ Cardiotoxicity ↑↑ Nephrotoxicity ↑↑ Hepatotoxicity ↑↑ VOD	Suspected	[4, 7, 8]
Ketoconazole	Strong inhibition of CYP3A4-mediated activation and detoxification of Cy Week inhibition of CYP2C19-mediated activation of Cy	Major	↑↑↑ Nephrotoxicity ↑↑↑ Hepatotoxicity	Suspected	[12]
Voriconazole	Strong inhibition of CYP3A4-mediated activation and detoxification of Cy Moderate inhibition of CYP2C19-mediated activation of Cy Week inhibition of CYP2C9-mediated activation of Cy Inhibition of CYP2B6-mediated activation of Cy	Moderate	N/A	Suspected	[9, 10]
Posaconazole	Strong inhibition of CYP3A4-mediated activation and detoxification of Cy	Moderate	N/A	Suspected	[11]
Echinocandins	No significant interaction	-	-	-	[13]
Amphotericin B (parenteral)	Synergist nephrotoxicity effects	Moderate	↑ Nephrotoxicity	Suspected	[14]
Amphotericin B (inhalation)	No significant interaction	-	-	-	[13]

Abbreviations: CYP: cytochrome P; Cy: cyclophosphamide; HSCT: hematopoietic stem cell transplantation; N/A: not available; Ref.: reference; VOD: veno-occlusive disease; ↑ increased; ↕ increased or decreased