Frequency, characteristics and risk factors of QT interval prolonging drugs and drug-drug interactions in cancer patients: A multicenter study

Abstract

Background: Cancer patients may receive a high number of medications with the potential to prolong QT interval and subsequent TdP (torsades de pointes). This study aimed to identify the prevalence of QT prolonging drugs, their TdP risk, QT prolonging drug-drug interactions (QT-DDIs), levels, predictors, and TdP risk of drugs involved in QT-DDIs. Methods: This multicenter study included cancer patients from three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. Micromedex DrugReax® was used for identification of QT-DDIs. TdP risks were identified by AZCERT (Arizona Center for Education and Research on Therapeutics) classification. Logistic regression analysis was performed to identify predictors of QT-DDIs. Results: Of 555 patients, 51% were females. Mean age was 46.9±15.7years. Total 28 distinct QT prolonging drugs were identified in 92.6% of the patients. Overall 21.8% patients were presented with QT-DDIs. Of total 288 identified QT-DDIs, all were of major-severity and fair-documentation. According to AZCERT classification, 59.9% of the interacting drugs were included in list-1 (known risk of TdP), 4.7% in list-2 (possible risk of TdP) and 6.8% in list-3 (conditional risk of TdP). Univariate logistic regression analysis showed significant results for various predictors such as, 8-9 prescribed medications (p<0.001) and ≥10 medications (p<0.001), 2 QT drugs (p<0.001) and ≥3 QT drugs (p<0.001), breast cancer (p=0.03), gastrointestinal cancer (p=0.03), 4-5 supportive care drugs (p<0.001), 6-8 supportive care drugs (p<0.001) and >8 supportive care drugs (p<0.001). Conclusions: A high prevalence of QT prolonging drugs and QT-DDIs was reported in oncology. Appropriate precautions are needed to prevent harmful consequences of these interactions.