An update on the safety and interactions of antifungal drugs in stem cell transplant recipients

Expert Opin Drug Saf. 2017 Mar;16(3):329-339. doi: 10.1080/14740338.2017.1273900. Epub 2016 Dec 26.

Abstract

Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Improvement in the management of IFDs have been achieved with the availability of new effective and safe antifungal drugs, however, many of these newer treatments have some limitations in their variable toxicity and unique predisposition for pharmacokinetic drug-drug interactions. Areas covered: This article is an update of a previous review published in this journal evaluating the safety profile of the antifungal drugs. Interesting new features include the availability of the new drug isavuconazole and the new tablet and intravenous formulations of posaconazole. Different dosages and new ways of administration of liposomal Amphotericin B (L-AmB) and echinocandins may be considered in the HSCT practice. Expert opinion: Nephrotoxicity continues to be a clinically relevant and frequent side effect of L-AmB which may cause a reduced clearance of other renally eliminated drugs frequently used in HSCT patients. Echinocandins are favorable therapeutic options in view of their low toxicity and uncommon drug-drug interactions. Important limitations of triazoles are represented by hepatic toxicity and certain side effects particularly after prolonged treatments. The new triazole isavuconazole and the new tablet formulation of posaconazole will be probably increasingly used in the HSCT setting not only due to their efficacy but in particular for their interesting toxicity profile and pharmacokinetic characteristics. The knowledge of these pharmacological findings is crucial in the daily care of allogeneic HSCT patients.

Keywords: Antifungals; allogeneic HSCT; interactions; toxicity.

Publication types

  • Review

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / adverse effects
  • Amphotericin B / pharmacokinetics
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / adverse effects
  • Antifungal Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Invasive Fungal Infections / drug therapy*
  • Invasive Fungal Infections / etiology
  • Nitriles / administration & dosage
  • Nitriles / adverse effects
  • Nitriles / pharmacokinetics
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / pharmacokinetics
  • Triazoles / administration & dosage
  • Triazoles / adverse effects
  • Triazoles / pharmacokinetics

Substances

  • Antifungal Agents
  • Nitriles
  • Pyridines
  • Triazoles
  • liposomal amphotericin B
  • isavuconazole
  • posaconazole
  • Amphotericin B