AE PO studies Cardiac AE Drug-related cardiac AE Serious cardiac AE Serious drug-related cardiac AE Cardiac AE with fatal outcome IV/PO studies Cardiac AE Drug-related cardiac AE Serious cardiac AE Serious drug-related cardiac AE Cardiac AE with fatal outcome Drug-related cardiac AE with fatal outcome All (Nb = 10,613) 698 (6.6) 342 (3.2) 75 (0.7) 7 (< 0.1) 12 (0.1) 0 (0) (N = 3431) 377 (11.0) 49 (1.4) 117 (3.4) 6 (0.2) 43 (1.3) 1 (< 0.1) Women (N = 5773) 409 (7.1) 248 (4.3) 21 (0.4) 3 (< 0.1) 3 (0.1) 0 (0) (N = 1349) 178 (13.2) 24 (1.8) 50 (3.7) 3 (0.2) 19 (1.4) 0 (0) Drug-related cardiac AE with fatal outcome AE = adverse event; PO = oral administration, IV/PO = sequential intravenous/oral administration. an = number of patients with event. bN = total number of patients in group. cFor a list of comparators see Table 1. 65 years (N = 2403) 176 (7.3) 36 (1.5) 35 (1.5) 3 (< 0.1) 12 (0.5) 0 (0) (N = 1334) 244 (18.3) 26 (1.9) 83 (6.2) 6 (0.4) 37 (2.8) 3 (0.2) Moxifloxacin, na (%) Comparatorsc, n (%) 65 years All Women (N = 2451) (N = 10,685) (N = 5817) 210 (8.6) 76 (3.1) 42 (1.7) 3 (0.1) 9 (0.4) 0 (0) (N = 1373) 213 (15.5) 22 (1.6) 83 (6.0) 5 (0.4) 32 (2.3) 0 (0) 619 (5.8) 256 (2.4) 72 (0.7) 6 (< 0.1) 21 (0.2) 1 (< 0.1) (N = 3415) 410 (12.0) 50 (1.5) 118 (3.5) 11 (0.3) 44 (1.3) 3 (< 0.1) 356 (6.1) 185 (3.2) 27 (0.5) 3 (< 0.1) 4 (0.1) 0 (0) (N = 1323) 181 (13.7) 23 (1.7) 49 (3.7) 6 (0.5) 15 (1.1) 1 (0.1) Update on the Cardiac Safety of Moxifloxacin Current Drug Safety, 2012, Vol. 7, No. 2 153 Table 3. Treatment-Emergent Cardiac AEs: Pooled Data from Phase II to IV Randomized Active-Controlled Studies with PO or IV/PO Moxifloxacin (moxifloxacin [3.5%]). 117/3431 [3.4%], comparators 118/3415 In women and patients over 65 years old (i.e. at higher risk of cardiac arrhythmias and other cardiac AEs), rates of treatment-emergent cardiac AEs were higher for IV/PO studies (13.2–18.3%) than for PO studies (6.1–8.6%), as observed in the overall population. Rates of serious cardiac AEs were also higher for IV/PO studies (3.7–6.2%) versus PO studies (0.4– 1.7%). A similar percentage of at-risk patients in each treatment arm experienced a treatment-emergent AE or serious cardiac treatment-emergent AE (Table 3). Treatment-Emergent Drug-Related AEs and Treatment- Emergent Drug-Related Serious AEs Treatment-emergent drug-related AEs are summarized in Table 3. In the PO group, 342/10,613 (3.2%) of moxifloxacin- and 256/10,685 (2.4%) of comparator-treated patients experienced a treatment-emergent drug-related cardiac AE. Equivalent numbers for the IV/PO group were 49/3431 (1.4%) for moxifloxacin and 50/3415 (1.5%) for comparator treatments. There were no clinically relevant differences in any type of treatment-emergent cardiac AEs between moxifloxacin and comparators in either the PO or IV/PO group. Treatment-emergent serious drug-related cardiac AEs were reported for 7 PO patients (< 0.1%) in the moxifloxacin group, and 6 (< 0.1%) in the comparator group, and for 6 (0.2%) versus 11 (0.3%) of IV/PO patients in the moxifloxacin and comparator arms, respectively. In women, there were no major clinically relevant differences between moxifloxacin and comparators in either the PO or IV/PO group with respect to the incidence of treatment-emergent drug-related cardiac AEs. In patients 65 years old, the only difference seen was in drug-related treatment-emergent AEs in PO studies. These were more frequent in the moxifloxacin than the comparator group (76/2451, 3.1% vs 36/2403, 1.5%, respectively), with the difference driven by a higher occurrence of dizziness (moxifloxacin 61/2451, 2.5% vs comparators 21/2403, 0.9%). Treatment-Emergent AEs and Fatal Outcome Drug-Related AEs with Treatment-emergent cardiac AEs with a fatal outcome were rare in the PO and IV/PO groups. In PO patients, there were 12 (0.1%) treatment-emergent cardiac AEs with a fatal outcome with moxifloxacin and 21 (0.2%) with comparators. Of these, none with moxifloxacin and only one (< 0.1%) with a comparator were considered drug-related. This patient had septicemia and died from cardiorespiratory failure. In the IV/PO group, there were 43 (1.3%) versus 44 (1.3%) treatment-emergent cardiac AEs with a fatal outcome for moxifloxacin and comparators, respectively. Of these, one with moxifloxacin and three with comparators were considered drug-related. The moxifloxacin-treated patient died after having ventricular tachycardia in the context of a myocardial infarction leading to hypotension and acute respiratory failure. Causes of death in the comparator arm were cardiac arrest secondary to bilateral lung infiltrates, acute myocardial infarction and acute cardiorespiratory failure, and ventricular tachycardia. The incidences of treatment-emergent cardiac AEs with fatal outcome in women were similar for moxifloxacin and