Update on the Cardiac Safety of Moxifloxacin Current Drug Safety, 2012, Vol. 7, No. 2 157 Moxifloxacin Administration route PO = 10,613 IV/PO CAP = 1511 IV/PO cSSSI = 1130 PO = 787 IV/PO CAP Group A = 384 Group B = 506 Group C = 596 IV/PO cSSSI Group A = 165 Group B = 515 Group C = 187 Total patients 28,144† Comparators Administration route PO = 10,685 IV/PO CAP = 1539 IV/PO cSSSI= 1077 PO = 759 IV/PO CAP Group A = 396 Group B = 516 Group C = 599 IV/PO cSSSI Group A = 164 Group B = 486 Group C = 179 ECG available‡ ECG available ‡ †Includes patients treated for indications other than cSSSI and CAP ‡Patients with valid ECG at baseline and post-baseline (PO); Group A = patients with ECG measurements at baseline, Day 1 and Day 3; Group B = patients with ECG measurements at baseline and Day 1; Group C = patients with ECG measurements at baseline and Day 3 Fig. (1). Patient Disposition Showing Numbers with Baseline and Post-Baseline ECG Data. there is the possibility that in rare cases a delay in cardiac repolarization could translate into serious cardiac events. For this reason, moxifloxacin is contraindicated or should be used with caution (depending on the countries) in patients with a range of pro-arrhythmic conditions [33, 34]. Individual clinical studies with moxifloxacin [11, 20-24] and an analysis of a large Phase II to IV data set (approximately 6000 patients) [35] have not found increased cardiac morbidity or mortality with moxifloxacin. The current analysis, which used extensive Phase II to IV randomized active-controlled clinical trials data for moxifloxacin, confirms the cardiac safety of moxifloxacin (PO and IV/PO) across a range of indications and in comparison with commonly used antibiotics, as seen in previous studies. In this large population of patients, the incidences of treatment-emergent cardiac AEs were similar for moxifloxacin and comparators; the larger number of cardiac AEs seen in IV/PO versus PO patients in both groups is likely to be explained by an increased frequency of cardiac comorbidities and the severity of patients. There was a low incidence of drug-related treatment-emergent cardiac AEs with both moxifloxacin and comparators and only five drug- related treatment-emergent deaths due to cardiac AEs in the entire population, one treated with a comparator in the PO group, one with IV/PO moxifloxacin, and three with IV/PO comparator agents. The incidence of drug-related cardiac AEs was higher in the PO population than in IV/PO population in both treatment groups. However, patients receiving IV/PO treatment are more likely to have cardiac- related co-morbidities and underlying conditions that may affect the reporting of cardiac AEs. There was no reported case of TdP in 14,044 moxifloxacin-treated patients. Even in patient populations at elevated risk of cardiac AEs due to the potential for underlying prolongations in QTc interval (i.e. women and those of least 65 years old), there was no evidence of any additional risk for treatment- emergent cardiac AEs. The patient subgroup with serious CAP was defined by admission to the ICU and/or requirement for mechanical ventilation. Such very ill patients who require initial parenteral antimicrobial treatment would be expected to have more cardiac risk factors than the wider populations of patients treated with antimicrobials for indications such as ABS, AECB, mild-to-moderate CAP, and cSSSI. The cardiac AE profiles in this high-risk population were similar for moxifloxacin and comparator groups and the incidence of treatment-emergent cardiac AEs considered potential surrogates for TdP/QTc prolongation with moxifloxacin was low. In the subset of patients with ECG measurements, the mean baseline QTcB interval was similar (about 420 ms) for moxifloxacin- and comparator-treated patients across PO and