Posaconazole achieves prompt recovery of voriconazole-induced liver injury in a case of invasive aspergillosis

Abstract

Azole antifungals have frequently been linked to the presence of hepatotoxicity, but there is scarce information on cross-toxicity between these drugs or on the possibility of using some of them when this type of toxicity occurs. We report the case of a 64-year-old man with invasive aspergillosis (IA) leading to spondylodiscitis with neurological involvement. Early management included intravenous (iv) voriconazole, which had to be interrupted after 1 week due to liver damage. Therapeutic drug monitoring (TDM) of voriconazole showed that the plasma concentration was within the therapeutic range. However, it was replaced by a combination therapy of oral posaconazole plus iv caspofungin. Posaconazole allowed normalization of liver enzymes. After finishing posaconazole monotherapy on an outpatient basis, the patient made a full recovery. This case report provides further evidence that oral posaconazole is safe and effective as rescue therapy after the appearance of voriconazole-induced liver toxicity.

Tolerability of isavuconazole after posaconazole toxicity in leukaemia patients

“…For example, switching to anidulafungin in the setting of caspofungin‐induced liver injury in 61 patients resulted in significant reduction in LFTs . Similarly, case reports and small retrospective studies utilising PCZ after voriconazole‐induced liver toxicity showed resolution of previous liver injury with successful treatment of invasive aspergillosis . These studies suggest hepatotoxicity to one azole does not predict future tolerability with other azoles, giving rationale to support switching therapy in this setting, although more investigations are needed.…”

“…The relative incidence of severe liver toxicity is variable between antifungal agents with voriconazole and PCZ appearing to have greater incidence of Grade 3/4 increase in LFTs than fluconazole and itraconazole . Although in our patients elevated LFTs are often due to many factors, such as the hematologic disease, chemotherapy treatment or from the underlying infection, studies estimate PCZ‐associated liver injury occurs in ~5%‐10% of patients …”

“…Clinical trials with ISA have shown a lower incidence of hepatotoxicity compared to voriconazole, and a shortening of the QTc interval on ECG . Given that azole‐induced hepatotoxicity is likely specific to the offending azole, it is possible ISA could be utilised in patients experiencing toxicity from PCZ . However, real‐world data are lacking regarding use of ISA after PCZ toxicity.…”

Invasive Pulmonary Aspergillosis

“…Posaconazole has activity against Mucorales. 41,42,[235][236][237] Combination Antifungal Therapy Only one large scale prospective randomized study on combination therapy has been conducted. It compared voriconazole plus placebo to voriconazole plus anidulafungin.…”

Pre-Existing Liver Disease and Toxicity of Antifungals

“…Noticeably, in patients with new-onset hepatotoxicity due to voriconazole administration for IFIs, sequential use of posaconazole seems to be safe and effective, with favorable outcomes and improvement of liver biochemistry in most of the cases [122,123,124]. Independently of the acute or chronic nature of pre-existing liver injury, no dosage adjustments are recommended for individuals with hepatic impairment treated with posaconazole [113].…”