Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections

Abstract

Dionissios Neofytos1, Edina Avdic2, Anna-Pelagia Magiorakos31Transplant and Oncology Infectious Disease Program, The Johns Hopkins University School of Medicine, Division of Infectious Diseases, 2Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, USA; 3Scientific Advice Unit, European Centre for Disease Prevention and Control, Stockholm, SwedenAbstract: There has been an increase in the number of patients susceptible to invasive fungal infections (IFIs) leading to a greater need for effective, well tolerated, and easily administered antifungal agents. The advent of triazoles has revolutionized the care of patients requiring treatment or prophylaxis for IFIs. However, triazoles have been associated with a number of adverse events and significant drug–drug interactions. While commonly used, physicians and patients should be aware of the distinct properties of these agents in order to ensure that patients are optimally treated with the least amount of toxicity possible. Clinicians should have a full understanding of the basic pharmacokinetics, absorption, and bioavailability of triazoles. Moreover, knowledge of the drug–drug interactions and potential toxicities of each agent is critical prior to administering a triazole. Careful history taking, thorough review of the patient’s medication list, and detailed discussion with the patients and their families about the efficacy, safety, and tolerability of these agents should be performed. Clinicians treating patients with triazoles should closely follow them, monitor pertinent laboratory tests, and consider measuring drug levels as needed. This article will review the basic pharmacokinetic properties and most frequently encountered adverse events and pitfalls associated with triazoles in clinical practice. Keywords: triazoles, fluconazole, voriconazole, posaconazole, itraconazole, review, invasive fungal infections, adverse events, drug–drug interactions