Antifungal agents and liver toxicity: a complex interaction.
The number of antifungal agents has sharply increased in recent decades. Antifungals differ in their spectrum of activity, pharmacokinetic/pharmacodynamic properties, dosing, safety-profiles and costs. Risk of developing antifungal associated hepatotoxicity is multifactorial and is influenced by pre-existing liver disease, chemical properties of the drug, patient demographics, comorbidities, drug-drug interactions, environmental and genetic factors. Antifungal related liver injury typically manifests as elevations in serum aminotransferase levels, although the clinical significance of these biochemical alterations is not always clear. Incidence rates of hepatotoxicity induced by antifungal therapy range widely, occurring most frequently in patients treated with azole antifungals for documented fungal infections.



This review provides an update regarding the hepatotoxicity profiles of the modern systemic antifungals used in treatment of invasive fungal infections. Expert commentary: Understanding the likelihood and pattern of hepatotoxicity for all suspected drugs can aid the clinician in early detection of liver injury allowing for intervention and potential mitigation of liver damage. Therapeutic drug monitoring is emerging as a potential tool to assess risk for hepatotoxicity.
a Department of Pharmacy Clinical Programs , The University of Texas M.D. Anderson Cancer Center , Houston , TX , USA.
Frank P
FP
Tverdek
b Infectious Disease Unit, Department of Internal Medicine , University Hospital of Heraklion , Crete , Greece.
Diamantis
D
Kofteridis
c Departments of Infectious Diseases , Infection Control and Employee Health, The University of Texas M.D. Anderson Cancer Center , Houston , TX , USA.
Dimitrios P
DP
Kontoyiannis
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D015994:Incidence; D000072742:Invasive Fungal Infections / Q000188:drug therapy* / Q000453:epidemiology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008111:Liver Function Tests
D000935:Antifungal Agents
Antifungal; azole; echinocandin; hepatotoxicity; liver; polyene; toxicity