title: Effect of combined fluoroquinolone and azole use on QT prolongation in hematology patients.
abstract: QTc prolongation is a risk factor for development of torsades de pointes (TdP). Combination therapy with fluoroquinolones and azoles is used in patients with hematologic malignancies for prophylaxis and treatment of infection. Both drug classes are implicated as risk factors for QTc prolongation. The cumulative effect on and incidence of QTc prolongation for this combination have not been previously described. A retrospective chart review was performed with hospitalized inpatients from 1 September 2008 to 31 January 2010 comparing QTc interval data from electrocardiogram (ECG) assessment at baseline and after the initiation of combination therapy. Ninety-four patients were eligible for inclusion. The majority, 88 patients (93.6%), received quinolone therapy with levofloxacin. Fifty-three patients (56.4%) received voriconazole; 40 (42.6%) received fluconazole. The overall mean QTc change from baseline was 6.1 (95% confidence interval [CI], 0.2 to 11.9) ms. Twenty-one (22.3%) of the studied patients had clinically significant changes in the QTc while receiving combination fluoroquinolone-azole therapy. Statistically significant risk factors for clinically significant changes in QTc were hypokalemia (P = 0.03) and a left-ventricular ejection fraction of <55% (P = 0.02). Low magnesium (P = 0.11), exposure to 2 or more drugs with the potential to prolong the QTc interval (P = 0.17), and female sex (P = 0.21) trended toward significance. Combination therapy with fluoroquinolone and azole antifungals is associated with increased QTc from baseline in hospitalized patients with hematologic malignancies. One in five patients had a clinically significant change in the QTc, warranting close monitoring and risk factor modification to prevent the possibility of further QTc prolongation and risk of TdP.
authors.affiliation: Hospital Pharmacy Services, Mayo Clinic, Rochester, MN, USA. zeuli.john@mayo.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Zeuli
authors.forename: John W
authors.initials: JW
authors.lastname: Wilson
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Estes
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000009:adverse effects*; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D006801:Humans; D007008:Hypokalemia / Q000503:physiopathology; D064704:Levofloxacin; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control; D015242:Ofloxacin / Q000008:administration & dosage / Q000009:adverse effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000517:prevention & control; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D064704:Levofloxacin; D015725:Fluconazole; D015242:Ofloxacin; D065819:Voriconazole