Spotlight on isavuconazole in the treatment of invasive aspergillosis and mucormycosis: design, development, and place in therapy

Drug Des Devel Ther. 2018 Apr 30:12:1033-1044. doi: 10.2147/DDDT.S145545. eCollection 2018.

Abstract

In recent decades, important advances have been made in the diagnosis and treatment of invasive aspergillosis (IA) and mucormycosis. One of these advances has been the introduction of isavuconazole, a second-generation broad spectrum triazole with a favorable pharmacokinetic and safety profile and few drug-drug interactions. Phase III trials in patients with IA and mucormycosis demonstrated that isavuconazole has similar efficacy to voriconazole for the treatment of IA (SECURE trial) and liposomal amphotericin B for the treatment of mucormycosis (VITAL trial with subsequent case-control analysis) and a favorable safety profile with significantly fewer ocular, hepatobiliary, and skin and soft tissue adverse events compared to voriconazole. As a result, recent IA guidelines recommend isavuconazole (together with voriconazole) as gold standard treatment for IA in patients with underlying hematological malignancies. In contrast to liposomal amphotericin B, isavuconazole can be safely administered in patients with reduced renal function and is frequently used for the treatment of mucormycosis in patients with reduced renal function. Updated guidelines on mucormycosis are needed to reflect the current evidence and give guidance on the use of isavuconazole for mucormycosis. Studies are needed to evaluate the role of isavuconazole for 1) anti-mold prophylaxis in high-risk patients, 2) salvage treatment for IA and mucormycosis, and 3) treatment for other mold infections such as Scedosporium apiospermum.

Keywords: SECURE; TDM; VITAL; plasma level; real life; susceptibility; triazole.

Publication types

  • Review

MeSH terms

  • Animals
  • Antifungal Agents / chemistry
  • Antifungal Agents / metabolism
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / drug therapy*
  • Drug Design*
  • Humans
  • Mucormycosis / drug therapy*
  • Nitriles / chemistry
  • Nitriles / metabolism
  • Nitriles / therapeutic use*
  • Pyridines / chemistry
  • Pyridines / metabolism
  • Pyridines / therapeutic use*
  • Triazoles / chemistry
  • Triazoles / metabolism
  • Triazoles / therapeutic use*

Substances

  • Antifungal Agents
  • Nitriles
  • Pyridines
  • Triazoles
  • isavuconazole