Safety and interactions of new antifungals in stem cell transplant recipients.
BACKGROUND
Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Considerable progress in treating IFDs has been achieved over the last years, through the availability of new, effective drugs. However, many of these newer antifungal agents have some limitations, such as their variable toxicity and unique predisposition for pharmacokinetic drug-drug interactions.


METHODS
This article reviews the literature evaluating the safety profile of the lipid formulations of Amphotericin B, echinocandins, and second-generation triazoles. It also discusses the possible drug-drug interactions with some drugs commonly used in allogeneic HSCT.


CONCLUSIONS
Nephrotoxicity is the most frequent side effect of lipid formulations of Amphotericin B, which may cause a reduced clearance of the renally eliminated calcineurin inhibitors used for the control of Graft Versus Host Disease. Second-generation triazoles are characterized by a limited toxicity profile, but also by frequent drug-drug interactions with other drugs metabolized by the hepatic enzymes. The echinocandins are characterized by a very low toxicity profile and negligible interactions with other drugs. Such pharmacological knowledge is crucial in the daily care of allogeneic HSCT patients.
Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, Via Benevento 6, 00161 Rome, Italy. girmenia@bce.uniroma1.it
Corrado
C
Girmenia
Anna Paola
AP
Iori
D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D054714:Echinocandins / Q000009:adverse effects / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D009181:Mycoses / Q000188:drug therapy*; D009894:Opportunistic Infections / Q000188:drug therapy*; D060735:Pharmacovigilance; D051437:Renal Insufficiency / Q000139:chemically induced; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use
D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D014230:Triazoles; D000666:Amphotericin B