Abstract
Second generation triazoles are widely used as first-line drugs for the treatment of invasive fungal infections, including aspergillosis and candidiasis. This class, along with itraconazole, voriconazole, posaconazole, and isavuconazole, is characterized by a broad range of activity, however, individual drugs vary considerably in safety, tolerability, pharmacokinetics profiles, and interactions with concomitant medications. The interaction may be encountered on the absorption, distribution, metabolism, and elimination (ADME) step. All triazoles as inhibitors or substrates of CYP isoenzymes can often interact with many drugs, which may result in the change of the activity of the drug and cause serious side effects. Drugs of this class should be used with caution with other agents, and an understanding of their pharmacokinetic profile, safety, and drug-drug interaction profiles is important to provide effective antifungal therapy. The manuscript reviews significant drug interactions of azoles with other medications, as well as with food. The PubMed and Google Scholar bases were searched to collect the literature data. The interactions with anticonvulsants, antibiotics, statins, kinase inhibitors, proton pump inhibitors, non-nucleoside reverse transcriptase inhibitors, opioid analgesics, benzodiazepines, cardiac glycosides, nonsteroidal anti-inflammatory drugs, immunosuppressants, antipsychotics, corticosteroids, biguanides, and anticoagulants are presented. We also paid attention to possible interactions with drugs during experimental therapies for the treatment of COVID-19.
Highlights
Non-steroidal anti-inflammatory drugs (NSAIDs) statins are the drugs that are widely used and their coadministration with voriconazole should be done with caution, as well for as herbal drugs
Due to the prolongation of QT-interval in patients treated with voriconazole it should be used cautiously in patients with COVID-19
Tacrolimus therapeutic drug monitoring (TDM) is recommended to individually guide tacrolimus dosing [135]. This finding appears to be similar to that reported by Kufel et al In that study, potential drug-drug interactions with tacrolimus and isavuconazole were predicted in allogeneic stem cell transplant patient
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Invasive fungal infections (IFI) are a serious clinical problem They are the result of a lack of immunity. Called the second generation of azoles, are represented by itraconazole, voriconazole, posaconazole, and isavuconazole [6,7] Their activity is based on the inhibition of ergosterol synthesis in the fungal cell, required for membrane integrity and the function of membrane associated proteins. The interaction in the metabolism step with the interaction with CYP enzymes may increase or decrease exposure on the drug This may result in a change of activity of the drug, from lacking any to serious side effects. The paper analyses the interactions with other drugs, and the impact of the fed state on the representatives of the second generation of antifungal drugs, i.e., itraconazole, voriconazole, posaconazole, and isavuconazole. There results are reported in both regular clinical trials and case studies
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