Drug–drug interactions of antifungal agents and implications for patient care

Abstract

Drug interactions in the gastrointestinal tract, liver and kidneys result from alterations in pH, ionic complexation, and interference with membrane transport proteins and enzymatic processes involved in intestinal absorption, enteric and hepatic metabolism, renal filtration and excretion. Azole antifungals can be involved in drug interactions at all the sites, by one or more of the above mechanisms. Consequently, azoles interact with a vast array of compounds. Drug-drug interactions associated with amphotericin B formulations are predictable and result from the renal toxicity and electrolyte disturbances associated with these compounds. The echinocandins are unknown cytochrome P450 substrates and to date are relatively devoid of significant drug-drug interactions. This article reviews drug interactions involving antifungal agents that affect other agents and implications for patient care are highlighted.

Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay

“…In spite of the clinical application of four classes of antimycotics against systemic candidiasis, there have been continuous efforts to discover and develop new antimycotic compounds, as existing drugs may be associated with toxic side-effects or interactions with other therapeutics, high costs and resistance development (Gubbins and Amsden, 2005;Vermes et al, 2000). Beside the screening for compounds with fungicidal or fungistatic activity and the description of novel potential antimycotic therapeutics (reviewed by Calugi et al (2011)), the recent years also saw the development of novel approaches to the search for antifungal agents (for example BurgerKentischer et al, 2011;Lafleur et al, 2011).…”

Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders

“…Busulphan levels are likely to be elevated 44 Cimetidine CSA trough levels increased 50-80%. 44,51 Monitor and reduce CSA dose by 50%. 45 Effect persists for some time after cessation of itraconazole 44,51 CSA AUC increased 70%.…”

“…44,51 Monitor and reduce CSA dose by 50%. 45 Effect persists for some time after cessation of itraconazole 44,51 CSA AUC increased 70%. Interaction likely (ketoconazole inhibits activation of ifosphamide); monitor for efficacy 49,53 Interaction possible (ketoconazole inhibits activation of ifosphamide); monitor for efficacy 49,53 51,56 Administer with cola beverage 45 Omeprazole level doubled; recommend omeprazole dose reduction.…”

“…May decrease posaconazole bioavailability 43 Prednisolone May increase steroid levels; monitor 53 Increased prednisolone levels (13-30%), but clinical impact not likely to be significant 51,57 Increased steroid levels (11-34%); monitor 42 Not documented…”

“…Itraconazole absorption from capsules decreased (30-60%); solution unaffected 45,51 Oral ranitidine has no impact on voriconazole plasma concentration May increase plasma concentrations of the vinca alkaloids and lead to neurotoxicity. Dose adjustment of the vinca alkaloid should be considered 45 May increase plasma concentrations of the vinca alkaloids and lead to neurotoxicity.…”