Triazole antifungal drug interactions-practical considerations for excellent prescribing.

Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug-drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents (see https://www.aspergillus.org.uk/antifungal-drug-interactions/). In this article, we address the common and less common, but serious, drug interactions observed in clinical practice with triazole antifungals, including a group of drugs that cannot be prescribed with all or most triazole antifungals (ivabradine, ranolazine, eplerenone, fentanyl, apomorphine, quetiapine, bedaquiline, rifampicin, rifabutin, sirolimus, phenytoin and carbamazepine). We highlight interactions with drugs used in children and new agents introduced for the treatment of haematological malignancies or graft versus host disease (midostaurin, ibrutinib, ruxolitinib and venetoclax). We also summarize the multiple interactions between oral and inhaled corticosteroids and triazole antifungals, and the strategies needed to optimize the therapeutic benefits of triazole antifungal therapy while minimizing potential harm to patients.

Broad spectrum antibiotic stewardship by quality improvement methods.

BACKGROUND: With the majority of antibiotics being prescribed in primary care it is of utmost importance that antimicrobial stewardship principles are adhered to in order to slow down the incidence of antimicrobial resistance. OBJECTIVE: Broad spectrum antibiotic prescribing is often seen as a proxy marker of increasing resistance within a population and so it is important that they are used sparingly, to avoid drug-resistant bacteria developing. METHOD: In Tameside and Glossop a novel approach, using quality improvement methods, was employed to allow the behaviour change to be sustained for a longer period. Practices submitted monthly broad spectrum usage data, and if over a set target they were required to submit a "deep dive". RESULTS: A 10.6% reduction of broad spectrum antibiotic usage was seen over the 2019-20 financial year. CONCLUSION: Over time the number of practices submitting a deep dive reduced and clinicians saw the deep dive as method to peer review their prescribing. Putting the practice staff in control of their own prescribing, allowed for a better method to sustain the improvement.

Drug-drug interaction database for safe prescribing of systemic antifungal agents.

INTRODUCTION: A drug-drug interaction (DDI) describes the influence of one drug upon another or the change in a drug's effect on the body when the drug is taken together with a second drug. A DDI can delay, decrease or enhance absorption or metabolism of either drug. Several antifungal agents have a large number of potentially deleterious DDIs. METHODS: The antifungal drug interactions database https://antifungalinteractions.org/was first launched in 2012 and is updated regularly. It is available as web and app versions to allow information on potential drug interactions with antifungals with a version for patients and another for health professionals. A new and updated database and interface with apps was created in 2019. This allows clinicians and patients to rapidly check for DDIs. The database is fully referenced to allow the user to access further information if needed. Currently DDIs for fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, terbinafine, amphotericin B, caspofungin, micafungin and anidulafungin are cross-referenced against 2398 other licensed drugs, a total of nearly 17,000 potential DDIs. RESULTS: The database records 541 potentially severe DDIs, 1129 moderate and 1015 mild DDIs, a total of 2685 (15.9%). CONCLUSION: As the online database and apps are free to use, we hope that widespread acceptance and usage will reduce medical misadventure and iatrogenic harm from unconsidered DDIs.