Antifungal-Associated Drug-Induced Cardiac Disease

Cleary, John D.; Stover, Kayla R.

doi:10.1093/cid/civ739

Cited by 16 publications

(14 citation statements)

References 22 publications

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“…However, recent data raise doubts about their safe use in critically ill patients with regard to hemodynamic stability (14)(15)(16). Several cases of severe hemodynamic instability following echinocandin infusion were reported, which led to the definition of an antifungal-associated drug-induced cardiac disease by Cleary et al (4)(5)(6)11). Cardiac impairment following echinocandin administration was reported in isolated rat cardiomyocytes (3).…”

mentioning

confidence: 99%

Caspofungin Modulates Ryanodine Receptor-Mediated Calcium Release in Human Cardiac Myocytes

Koch

Jersch

Schneck

et al. 2018

Antimicrob Agents Chemother

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Recent studies showed that critically ill patients might be at risk for hemodynamic impairment during caspofungin (CAS) therapy. The aim of our present study was to examine the mechanisms behind CAS-induced cardiac alterations. We revealed a dose-dependent increase in intracellular Ca concentration ([Ca]) after CAS treatment. Ca ions were found to be released from intracellular caffeine-sensitive stores, most probably via the activation of ryanodine receptors.

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mentioning

confidence: 99%

Caspofungin Modulates Ryanodine Receptor-Mediated Calcium Release in Human Cardiac Myocytes

Koch

Jersch

Schneck

et al. 2018

Antimicrob Agents Chemother

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“…While drugs within all 4 classes of systemic antifungals (azoles, polyene macrolides, allylamines, and echinocandins) have shown cardiovascular effects, echinocandins generally are the most well tolerated . Rezafungin, a new echinocandin, did not demonstrate an adverse effect on QT interval at therapeutic (600 mg) and supratherapeutic doses (1400 mg) in healthy male and female subjects in this definitive QT/QTc study.…”

Section: Discussionmentioning

confidence: 65%

Lack of Effect of Rezafungin on QT/QTc Interval in Healthy Subjects

Flanagan

Goodman

Jandourek

et al. 2019

Clinical Pharm in Drug Dev

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Rezafungin is a new echinocandin in development for treatment of candidemia and invasive candidiasis,and for prophylaxis of invasive fungal infections. Rezafungin is the first echinocandin to undergo definitive QT/QTc study. This phase 1, single-center, randomized, double-blind trial was conducted to assess effects of intravenous rezafungin vs intravenous placebo (with moxifloxacin as positive control) on the QT interval of the electrocardiogram, corrected for heart rate by Fridericia's formula (QTcF), in healthy adults. Therapeutic (600 mg) and supratherapeutic (1400 mg) rezafungin doses were selected to achieve exposures 2.5-fold higher than produced by the highest dose used in a phase 2 trial (400 mg once weekly). The primary end point was change in QTcF from baseline ( QTcF) as a function of plasma concentration, assessed by comparing upper bounds of the 2-sided 90% confidence interval. The estimated mean QTcF at the mean plasma concentrations for the rezafungin doses had upper bounds <10 milliseconds, within the upper bound of the 2-sided 90% confidence interval. Intravenous rezafungin up to 1400 mg in a single dose did not prolong QT interval and had no apparent effect on repolarization or QRS duration. Electrocardiogram results showed no clinically significant effects of concern. These findings support the continued development of rezafungin.

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“…In granulocytopenic patients with invasive candidosis, a higher dose of caspofungin (150 mg/d) led to higher response rates as compared to the standard dose (50 mg/d) 73 . It remains unclear whether patients with IA may benefit clinically from a higher daily dose of caspofungin or do have an increased risk for toxicity (eg cardiac toxicity) 74 …”

Section: Resultsmentioning

confidence: 99%

“…Amphotericin B lipid complex (ABLC) : A retrospective analysis of a large company‐based dataset (Collaborative Exchange of Antifungal Research; CLEAR) showed a 44% efficacy in about 400 patients with IA (55% response in 42 granulocytopenic patients), 31 and 31% response rate in patients after allogeneic stem cell transplantation, 74 mainly in patients with second‐line therapy (BIII). Therefore, ABLC is not regarded as first choice for first‐line therapy of IA (DI).…”

Section: Resultsmentioning

confidence: 99%

Treatment of invasive fungal diseases in cancer patients—Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

Ruhnke

Cornely

Schmidt‐Hieber

et al. 2020

Mycoses

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Summary Background Invasive fungal diseases remain a major cause of morbidity and mortality in cancer patients undergoing intensive cytotoxic therapy. The choice of the most appropriate antifungal treatment (AFT) depends on the fungal species suspected or identified, the patient's risk factors (eg length and depth of granulocytopenia) and the expected side effects. Objectives Since the last edition of recommendations for ‘Treatment of invasive fungal infections in cancer patients’ of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) in 2013, treatment strategies were gradually moving away from solely empirical therapy of presumed or possible invasive fungal diseases (IFDs) towards pre‐emptive therapy of probable IFD. Methods The guideline was prepared by German clinical experts for infections in cancer patients in a stepwise consensus process. MEDLINE was systematically searched for English‐language publications from January 1975 up to September 2019 using the key terms such as ‘invasive fungal infection’ and/or ‘invasive fungal disease’ and at least one of the following: antifungal agents, cancer, haematological malignancy, antifungal therapy, neutropenia, granulocytopenia, mycoses, aspergillosis, candidosis and mucormycosis. Results AFT of IFDs in cancer patients may include not only antifungal agents but also non‐pharmacologic treatment. In addition, the armamentarium of antifungals for treatment of IFDs has been broadened (eg licensing of isavuconazole). Additional antifungals are currently under investigation or in clinical trials. Conclusions Here, updated recommendations for the treatment of proven or probable IFDs are given. All recommendations including the levels of evidence are summarised in tables to give the reader rapid access to key information.

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Antifungal-Associated Drug-Induced Cardiac Disease

Cited by 16 publications

References 22 publications

Caspofungin Modulates Ryanodine Receptor-Mediated Calcium Release in Human Cardiac Myocytes

Caspofungin Modulates Ryanodine Receptor-Mediated Calcium Release in Human Cardiac Myocytes

Lack of Effect of Rezafungin on QT/QTc Interval in Healthy Subjects

Treatment of invasive fungal diseases in cancer patients—Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

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