Safety of triazole antifungal drugs in patients with cancer

Abstract

Triazole drugs are widely used in cancer patients for prophylaxis and treatment of life-threatening invasive fungal infections. Fluconazole, available for over two decades, is safe and effective in patients with cancer; however, the excellent safety profile of fluconazole may not be applicable to the newer triazoles. Itraconazole, voriconazole and posaconazole are associated with adverse events, and drug interactions frequently occur, particularly in cancer patients, since the triazoles and many drugs used in cancer chemotherapy are metabolized via a common metabolic pathway, the hepatic cytochrome P450 system. Close monitoring for drug interactions is needed when triazoles are used with anti-neoplastic drugs and dosage modification of the triazole or its discontinuation may be required. Monitoring of triazole serum concentrations is becoming an important aspect of management to minimize toxicity and ensure efficacy.

Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period

“…The Cologne group, 10 in contrast, reported no significant intolerance/toxicities associated with posaconazole, perhaps reflecting a higher degree of clinician confidence in the drug even in the presence of mucositis. Serious adverse events were consistent with the recognized toxicities of azoles 18 but for voriconazole, less frequent than post-marketing reports. 19,20 The emergence of resistant fungi is a potential drawback of broad-spectrum antifungal prophylaxis.…”

Assessing liver injury associated with antimycotics: Concise literature review and clues from data mining of the FAERS database

“…Previous studies, mostly based on data derived from clinical trials, reported a 2%-23% range, depending on the drug of interest and especially the severity of the disease [28] . Clinical evidence on ketoconazole emerged in early 80', when 54 reports of alleged ketoconazoleinduced liver injury submitted to the FDA from the time of initial marketing in 1980, of which 33 were labeled as likely.…”

Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

“…Considering that almost all fungal pathogens isolated during posaconazole PAP were susceptible in vitro to the triazole (unreported data), the possibility of reduced absorption, with sub-therapeutic serum concentrations of posaconazole, must be considered. [23][24][25] Many factors, such as the development of mucositis, impaired dietary intake and use of proton pump inhibitors may cause interindividual pharmacokinetic variability in AML patients, and therapeutic drug monitoring may be required. [23][24][25][26][27][28] Unlike previous studies showing impaired sensitivity of the GM assay in patients on antifungal therapy, 29 in our experience GM retained a major role in the diagnosis of IA also in patients receiving posaconazole.…”

“…[23][24][25] Many factors, such as the development of mucositis, impaired dietary intake and use of proton pump inhibitors may cause interindividual pharmacokinetic variability in AML patients, and therapeutic drug monitoring may be required. [23][24][25][26][27][28] Unlike previous studies showing impaired sensitivity of the GM assay in patients on antifungal therapy, 29 in our experience GM retained a major role in the diagnosis of IA also in patients receiving posaconazole. Assuming that reduced absorption of posaconazole, leading to subtherapeutic serum concentrations, could explain the occurrence of breakthrough IA, normal production and spread of GM by the fungal pathogen in these cases seems to be likely.…”