Voriconazole-Induced QT Interval Prolongation and Ventricular Tachycardia: A Non--Concentration-Dependent Adverse Effect

Alkan, Yoav; Haefeli, Walter E.; Burhenne, Jürgen; Stein, Joseph Allen; Yaniv, Isaac; Shalit, Itamar

doi:10.1086/423275

Cited by 65 publications

(61 citation statements)

References 8 publications

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“…A 15-year-old patient with acute lymphoblastic leukemia and fusarium infection was treated with a newer azole agent, voriconazole. She developed asymptomatic bradycardia, QT interval prolongation, and non-sustained, polymorphic ventricular tachycardia, which recurred upon rechallenge with the drug [49].…”

Section: Antifungalsmentioning

confidence: 99%

Proarrhythmic Potential of Antimicrobial Agents

et al. 2008

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Several antiarrhythmic and non-cardiovascular drug therapies including antimicrobial agents have been implicated as the causes for QT interval prolongation, torsades de pointes (TdP) ventricular tachycardia and sudden cardiac death. Most of the drugs that have been associated with the lengthening of the QT interval or development of TdP can also block the rapidly activating component of the delayed rectifier potassium current (IKr) in the ventricular cardiomyocytes. This article presents a review of the current literature on the QT interval prolonging effect of antimicrobials based on the results of the in vitro, in vivo studies and case reports. Our observations were derived from currently available Medline database. As we found, the most frequently QT interval prolonging antimicrobials are erythromycin, clarithromycin, fluoroquinolones, halofantrine, and pentamidine. Almost every antimicrobial-associated QT interval prolongation occurs in patients with multiple risk factors of the following: drug interactions, female gender, advanced age, structural heart disease, genetic predisposition, and electrolyte abnormalities. In conclusion, physicians should avoid prescribing antimicrobials having QT prolonging potential for patients with multiple risk factors. Recognition and appropriate treatment of TdP are also indispensable.

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Section: Antifungalsmentioning

confidence: 99%

Proarrhythmic Potential of Antimicrobial Agents

et al. 2008

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“…A number of studies have shown that adverse events associated with DDIs from the concomitant use of triazoles and other drugs could result in increased toxicity or QTc prolongation (27)(28)(29)(30)(31)(32). These interactions can be dangerous, especially among patients receiving chemotherapy or solid organ transplantation or critically ill patients treated in an ICU (33).…”

Section: Discussionmentioning

confidence: 99%

Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients

Andes

Azie

Yang

et al. 2016

Antimicrob Agents Chemother

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“…In contrast, other treatment studies did not observe peripheral neuropathy as an adverse event [9]. QTc interval prolongation has been described for voriconazole, intraconazole and posaconazole, and may be potentiated if those azoles are administered together with quinolones [19][20][21]. In contrast, isavuconazole is associated with a shortened QTc interval with a mean decrease of 36.5 ± 38.8 ms (7.4 ± 5.8%) compared to the pre-isavuconazole electrocardiogram in a recent study [22].…”

Section: Adverse Events Drug-drug Interaction and Therapeutic Drug Mmentioning

confidence: 98%

Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives

et al. 2018

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Chronic pulmonary aspergillosis (CPA) complicates conditions including tuberculosis, chronic obstructive pulmonary disease and sarcoidosis, and is associated with high morbidity and mortality. Surgical cure should be considered where feasible; however, many patients are unsuitable for surgery due to extensive disease or poor respiratory function. Azoles are the only oral drug with anti-Aspergillus activity and itraconazole and voriconazole are considered as first-line drugs. A randomized controlled trial demonstrated improvement or stability in three-quarters of patients given 6 months of itraconazole, but a quarter relapsed on stopping therapy. Long-term treatment may therefore be required in some cases. Itraconazole, voriconazole and posaconazole require therapeutic drug monitoring. No published data are yet available for isavuconazole. Adverse drug effects of azoles are common, including peripheral neuropathy, heart failure, elevated liver enzymes, QTc prolongation and sun sensitivity. Many serious drug-drug interactions occur, including major interactions with rifamycins, simvastatin, warfarin, clopidogrel, immunosuppressant drugs like sirolimus. Furthermore, drug resistance occurs, including cross-resistance to all azoles, but the true prevalence is not yet determined. Intravenous therapy is possible with echinocandins or amphotericin B, but long-term use is challenging. Hemoptysis complicates CPA and can be fatal. Tranexamic acid should be given acutely to reduce bleeding. Bronchial artery embolization can stop acute bleeds. In some circumstances, emergency surgery may be necessary to resect the source of the bleed. Current CPA treatments can be beneficial but have many drawbacks. New oral anti-Aspergillus agents are needed, along with optimization of currently available treatments.

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Voriconazole-Induced QT Interval Prolongation and Ventricular Tachycardia: A Non--Concentration-Dependent Adverse Effect

Cited by 65 publications

References 8 publications

Proarrhythmic Potential of Antimicrobial Agents

Proarrhythmic Potential of Antimicrobial Agents

Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients

Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives

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