Clinical hepatotoxicity associated with antifungal agents

@article{Kyriakidis2016ClinicalHA,
  title={Clinical hepatotoxicity associated with antifungal agents},
  author={Ioannis Kyriakidis and Athanasios Tragiannidis and Silke Munchen and Andreas H. Groll},
  journal={Expert Opinion on Drug Safety},
  year={2016},
  volume={16},
  pages={149 - 165}
}
ABSTRACT Introduction: Invasive fungal diseases (IFDs) are a leading cause of morbidity and mortality among immunocompromised patients with bone marrow failure syndromes, hematological malignancies, hematopoietic stem cell transplantation (HSCT), those admitted in intensive care units (ICUs) and those with prolonged febrile neutropenia. IFDs occur in a setting of multiple morbidities and are associated with case fatality rates between 30 and 70%. Along with the development of classes and… 

Antifungal agents and the kidney: pharmacokinetics, clinical nephrotoxicity, and interactions

The present article reviews incidence, severity and mechanisms of nephrotoxicity associated with antifungal agents used for prevention and treatment of invasive fungal diseases by discussing distribution, metabolism, elimination and drug-related adverse events in the context of safety data from phase II and III clinical studies.

Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents

Azole antifungals are first-line options in the prophylaxis and treatment of invasive fungal infections and have been associated with peripheral neuropathies, and itraconazole and voriconazole with pancreatitis.

Hepatotoxicity Due to Azole Antimycotic Agents in a HLA B*35:02-Positive Patient

A 42-year-old woman with acute myeloid leukemia and pulmonary aspergillosis treated with several antifungal agents, including three triazoles is presented, which suggests a cross-toxicity, dose-dependency, and a possible genetic predisposition of triazole-induced liver injury.

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

This case report provides further evidence that oral posaconazole is safe and effective as rescue therapy after the appearance of voriconazole-induced liver toxicity.

Therapeutic drug monitoring and safety evaluation of voriconazole in the treatment of pulmonary fungal diseases

Almost one-third of patients with pulmonary fungal disease needed to adjust their dose after the standard dose of voriconazole treatment, suggesting initial therapeutic drug monitoring (TDM) might predict the risk of hepatotoxicity.

Pre-Existing Liver Disease and Toxicity of Antifungals

This article provides suggestions for dosage adjustment of antifungal drugs in patients with varying degrees of hepatic impairment, after accounting for established or emerging pharmacokinetic–pharmacodynamic relationships with regard to antifundal drug efficacy in vivo.

Hepatic safety of the antifungal triazole agent posaconazole: characterization of adverse event reports in a manufacturer’s safety database

Use of concomitant medications with known risks for hepatic injury appears to be an important contributor for the development of hepatotoxicity in patients treated with posaconazole.

Voriconazole-Induced Acute Liver Injury: A Case Report

A 61-year-old lady with a past medical history of sarcoidosis, stage IV and severe pulmonary hypertension initially admitted for the management of COVID pneumonia is reported, eventually culminating in mortality due to acute liver injury diagnosed was most probably related to voriconazole.
...

References

SHOWING 1-10 OF 150 REFERENCES

The hepatotoxicity of antifungal medications in bone marrow transplant recipients.

In patients who developed hepatotoxicity and who continued receiving antifungal medication, one-third of those receiving liposomal amphotericin B had marked increases in bilirubin levels, as opposed to 8% of patients treated with fluconazole.

Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis

With the advent of newer classes of systemic antifungal agents, future trials should conform to definitions that are universally applicable and clinically relevant to allow for such comparisons and to enable evidence-based decision-making.

Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients

Several new agents such as voriconazole and caspofungin have enhanced potency and broad-spectrum antifungal activity and show promising results against yeasts and filamentous fungi when given as therapy and as chemoprophylaxis, thereby potentially decreasing cost and toxicity in high-risk patients.

Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.

  • J. MaertensI. Raad T. Walsh
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2004
Caspofungin demonstrated usefulness in the salvage treatment of IA and was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated asperGillosis.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT).

  • A. UllmannM. Akova M. Cuenca‐Estrella
  • Medicine, Biology
    Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
  • 2012
This part of the ESCMID guidelines focuses on this patient population and reviews pertaining to prophylaxis, empirical/pre-emptive and targeted therapy of Candida diseases, although a warning for resistance is expressed.

Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections

It is suggested that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation.

New and emerging treatments for fungal infections.

Overall these new antifungal agents in development offer extended half-lives, possibly reduced drug interaction profiles and good tolerance, and are probably similar to voriconazole and caspofungin (aminocandin).

Terbinafine-associated hepatotoxicity.

7,7-dimethylhept-2-ene-4-ynal (TBF-A), the allylic aldehyde metabolite of terbinafine, may play a role in the pathogenesis of its hepatotoxicity.
...