Quinidine is associated with arrhythmias, and a recent case series of patients hospitalized in the USA with malaria noted that four of six patients receiving quinidine experienced QT prolongation and two of six patients experienced Torsades de Pointes, a life-threatening arrhythmia associated with QT prolongation [ 58].
A total of 6 subjects were withdrawn from the quinidine study due to AEs, which included 2 subjects with positive FOB, 1 subject who experienced QTc prolongation after quinidine dosing, 1 subject with low hemoglobin, 1 subject with an increase in creatine kinase, and 1 subject with headache and nausea.
Three patients experienced QTc prolongation at higher dose levels on Cycle 1 Day 1 post-dose when QT = 438 ms, and QTc = 457 (QT with Bazett correction); however, a repeat ECG performed later on the same day showed resolution of the reported changes, with QT = 414 ms and QTc = 433.
The lower daily dosage of RPV is due to the fact that healthy, non-infected human volunteers experienced QT prolongations at doses of 75 mg or higher [ 106].
Nevertheless, despite more favorable features of the second transplant group, it was disappointing that such patients did not experience an important prolongation of survival with the procedure.
A serious AE is defined as any adverse event resulting in any of the following outcomes: death, a life-threatening adverse experience, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect resulting from a pregnancy.
malignant glioma xenografts treated with ZD6474 experienced a significant prolongation of survival.
At the MTD, ST segment and T-wave changes suggested ischaemic cardiac toxicity in three out of four patients and one patient experienced a QT prolongation.
The only patient with a known history of ischemic heart disease did not experience hypertension or QTc prolongation.
Serious adverse events were defined as, amongst others, a life-threatening experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity or death.
"Serious," by the FDA's definition, are those events that result in "Death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect".
