Clinically relevant drug interactions of current antifungal agents

Abstract

SummaryAntifungal agents are often prescribed in critically ill patients who are receiving many other medications. When using systemic antifungals, clinicians may possess susceptibility data and they are typically aware of the potential toxicity of these agents. However, the myriad of potential drugs that antifungal agents can interact with is daunting and can be confusing. This article reviews the pharmacokinetic properties of antifungal agents and their clinically relevant drug interactions. The antifungal agents differ markedly in their pharmacokinetic properties and in how they interact with other medicines. The amphotericin B formulations interact with other medicines primarily by reducing their renal elimination or producing additive toxicities. The azoles interact with other medicines primarily by inhibiting biotransformation or by affecting drug distribution and elimination. The echinocandins have the lowest propensity to interact with other medicines. The clinical relevance of antifungal-drug interactions varies substantially. While certain interactions are benign and result in little or no untoward clinical outcomes, others can produce significant toxicity or compromise efficacy if not properly managed through monitoring and dosage adjustment. However, certain interactions produce significant toxicity or compromise efficacy to such an extent that they cannot be managed and the particular combination of antifungal and interacting medicine should be avoided.

Renal Handling of Amphotericin B and Amphotericin B-Deoxycholate and Potential Renal Drug-Drug Interactions with Selected Antivirals

“…Because AmB-DOC inhibitory concentrations were higher by several orders of magnitude than the therapeutic concentrations, the probability of these drug-drug interactions at hOAT1 can be considered to be minimal in in vivo conditions. This finding is in accordance with the absence of any pharmacokinetic interactions between AmB and antivirals studied in the available clinical literature (1,36). Our in vitro results regarding hOAT1 led us to discontinue further experiments on the contribution of the individual components of AmB-DOC to the observed drug-drug interaction with hOAT1, as such studies might be expected to be clinically irrelevant.…”

“…However, no clinically relevant drugdrug interaction with AmB caused by an effect on membrane transport mechanisms has been described in the existing literature (1,36). The clinical drug-drug interactions involving AmB found in clinical conditions so far have been suggested to be based only on the toxicological effects of the drug which are additive to those of other drugs (e.g., cyclosporine, tacrolimus, digoxin, and aminoglycosides) or which reduce the elimination of concomitantly administered agents (5-flucytosine) (1,36). If we consider that the total concentrations of AmB in plasma following regular therapeutic doses have been found to be at a maximum between 1 and 5 M (34, 37), the effective inhibitory concentrations starting at about 1 to 2 M in this study (Fig.…”

Melanized Fungi in Human Disease

“…formulation. All of these agents have significant drug interactions that must be considered during therapy (310). In addition, therapeutic drug monitoring is becoming increasingly utilized as data correlating serum levels with clinical response and toxicity accumulate (706).…”

Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives

“…Especially the drug-drug interaction between rifamycins and triazoles has to be considered since patients with pulmonary tuberculosis have an increased risk to develop CPA coinfection. Concomitant use of rifamycins and triazoles should be avoided in patients with drug-susceptible pulmonary tuberculosis with CPA coinfection or in patients with nontuberculous mycobacterial pulmonary diseases [24,25]. Echinocandins may be considered as alternative antifungal drugs, but evidence is limited [26].…”