title: No Untoward Effect of Long-Term Ketoconazole Administration on Electrocardiographic QT Interval in Patients with Cushing's Disease.
abstract: Ketoconazole is listed among drugs that prolong QT interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushing's syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged QT interval, for example hypokalaemia and left ventricular hypertrophy, but no study has evaluated whether administration of ketoconazole affects their QT interval. The aim of this study was to assess the QT interval in patients with Cushing's disease during long-term administration of ketoconazole. Electrocardiograms from 15 patients with Cushing's disease (12 women, 3 men, age: 37.8 ± 2.66 years) on ketoconazole treatment (100 mg-800 mg qd) for 1 month to 12 years were reviewed retrospectively. QT interval was measured and corrected for heart rate (QTc). Measurements before and during ketoconazole treatment were compared and any abnormal QTc value recorded. Concurrent medical therapies were also documented. On average, QTc was superimposable before and during ketoconazole treatment (393.2 ± 7.17 versus 403.3 ± 6.05 msec. in women; 424.3 ± 23.54 versus 398.0 ± 14.93 msec. in men, N.S.). QTc normalized on ketoconazole in one man with prolonged QTc prior to treatment; no abnormal QTc was observed in any other patient during the entire observation period, even during concurrent treatment with other QT-prolonging drugs. In conclusion, long-term ketoconazole administration does not appear to be associated with significant prolongation of QT interval in patients with Cushing's disease. ECG monitoring can follow recommendations drawn for other low-risk QT-prolonging drugs with attention to specific risk factors, for example hypokalaemia and drug interactions.
authors.affiliation: Neuroendocrinology Research Laboratory, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: De Martin
authors.affiliation: Division of Endocrinology and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Paola Maria
authors.initials: PM
authors.lastname: Toja
authors.affiliation: Department of Geriatrics and Cardiovascular Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Karine
authors.initials: K
authors.lastname: Goulene
authors.affiliation: Neuroendocrinology Research Laboratory, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Radaelli
authors.affiliation: Neuroendocrinology Research Laboratory, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavagnini
authors.affiliation: Department of Geriatrics and Cardiovascular Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Stramba-Badiale
authors.affiliation: Neuroendocrinology Research Laboratory, IRCCS Istituto Auxologico Italiano, Milan, Italy.|Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pecori Giraldi
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000652:urine; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007654:Ketoconazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008133:Long QT Syndrome / Q000139:chemically induced / Q000209:etiology*; D008297:Male; D047748:Pituitary ACTH Hypersecretion / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies
chemical_list: D000324:Adrenocorticotropic Hormone; D007654:Ketoconazole; D006854:Hydrocortisone