I Gueta1,2, R Loebstein3,4, N Markovits3,4, Y Kamari4,5, H Halkin3,4, G Livni4,6, H Yarden-Bilavsky3,4. 1. Institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, 52621, Ramat Gan, Israel. Itai.Gueta@sheba.health.gov.il. 2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Itai.Gueta@sheba.health.gov.il. 3. Institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, 52621, Ramat Gan, Israel. 4. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. The Bert Strassburger Lipid Center, Sheba Medical Center, Ramat Gan, Israel. 6. Department of Pediatrics A, Schneider Children's Medical Center, Petah Tiqva, Israel.
Abstract
PURPOSE: The purpose of this study is to determine the rate of QTcP and associated risk factors in patients treated with voriconazole. METHODS: We conducted a retrospective chart review of all patients treated with voriconazole in a large tertiary center between 2009 and 2015, using paired comparison of QTc intervals on and off voriconazole treatment, adjusted for comorbidities, electrolyte abnormalities, and concurrent medications. RESULTS: Fifty-four patients were included, of whom 53 were diagnosed with oncologic/hemato-oncologic disease. Mean QTc during voriconazole therapy (448.0 ± 52.9 msec) was significantly longer compared to QTc off voriconazole (421.8 ± 42.2 msec; p = 0.002). QTcP ≥30 msec and ≥60 msec was demonstrated in 43% (23 patients) and 28% (15 patients), respectively. Multivariate analysis showed that QTcP was significantly associated with baseline QTc ≥ 450 msec (upper QTc quartile) (p < 0.01) and low serum potassium levels (p < 0.01). Contrarily, no significant association was found between mean voriconazole daily and cumulative dose and QTcP. CONCLUSION: Our findings indicate that hemato-oncologic patients treated with voriconazole are at increased risk for QTcP, especially in the presence of baseline QTc ≥ 450 msec and low serum potassium levels.
PURPOSE: The purpose of this study is to determine the rate of QTcP and associated risk factors in patients treated with voriconazole. METHODS: We conducted a retrospective chart review of all patients treated with voriconazole in a large tertiary center between 2009 and 2015, using paired comparison of QTc intervals on and off voriconazole treatment, adjusted for comorbidities, electrolyte abnormalities, and concurrent medications. RESULTS: Fifty-four patients were included, of whom 53 were diagnosed with oncologic/hemato-oncologic disease. Mean QTc during voriconazole therapy (448.0 ± 52.9 msec) was significantly longer compared to QTc off voriconazole (421.8 ± 42.2 msec; p = 0.002). QTcP ≥30 msec and ≥60 msec was demonstrated in 43% (23 patients) and 28% (15 patients), respectively. Multivariate analysis showed that QTcP was significantly associated with baseline QTc ≥ 450 msec (upper QTc quartile) (p < 0.01) and low serum potassium levels (p < 0.01). Contrarily, no significant association was found between mean voriconazole daily and cumulative dose and QTcP. CONCLUSION: Our findings indicate that hemato-oncologicpatients treated with voriconazole are at increased risk for QTcP, especially in the presence of baseline QTc ≥ 450 msec and low serum potassium levels.
Entities:
Keywords:
Adverse effects; QT prolongation; Safety; Torsade de pointes; Voriconazole
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