erence was 1.2% (95% CI -1.0, 3.4) between TYGACIL and comparator treated patients. No significant differences were observed between TYGACIL and comparators within each infection type (see Table 2). The cause of the imbalance has not been established. Generally, deaths were the result of worsening or complications of infection or underlying co-morbities.
Table 2. Patients with Adverse Events with Outcome of Death by Infection Type TYGACIL Comparator Risk Difference*
Infection Type n/N % n/N % % (95% CI)
CAP = Community-acquired pneumonia; cIAI = Complicated intra-abdominal infections; cSSSI = Complicated skin and skin structure infections; HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia; RP = Resistant pathogens; DFI = Diabetic foot infections.
* The difference between the percentage of patients who died in TYGACIL and comparator treatment groups.
a These are subgroups of the HAP population.
Note: The studies include 300, 305, 900 (cSSSI), 301, 306, 315, 316, 400 (cIAI), 308 and 313 (CAP), 311 (HAP), 307 [Resistant gram-positive pathogen study in patients with MRSA or Vancomycin-Resistant Enterococcus (VRE)], and 319 (DFI with and without osteomyelitis).
Approved Indications
cSSSI 12/834 1.4 6/813 0.7 0.7 (-0.5, 1.9)
cIAI 40/1382 2.9 27/1393 1.9 1.0 (-0.3, 2.2)
CAP 12/424 2.8 11/422 2.6 0.2 (-2.3, 2.7)
Combined 64/2640 2.4 44/2628 1.7 0.7 (-0.0, 1.6)
Unapproved Indications
HAP 65/467 13.9 56/467 12.0 1.9 (-2.6, 6.4)
Non-VAPa 40/336 11.9 42/345 12.2 -0.3 (-5.4, 4.9)
VAPa 25/131 19.1 14/122 11.5 7.6 (-2.0, 16.9)
RP 11/128 8.6 2/43 4.7 3.9 (-9.1, 11.6)
DFI 7/553 1.3 3/508 0.6 0.7 (-0.8, 2.2)
Combined 84/1148 7.2 61/1018 6.0 1.2 (-1.0, 3.4)
In comparative clinical studies, infection-related serious adverse events were more frequently reported for subjects treated with TYGACIL (7%) versus comparators (6%). Serious adverse events of sepsis/septic shock were more frequently reported for subjects treated with TYGACIL (2%) versus comparators (1%). Due to baseline differences between treatment groups in this subset of patients, the relationship of this outcome to treatment cannot be established [see Warnings and Precautions (5.8)].
The most common treatment-emergent adverse reactions were nausea and vomiting which generally occurred during the first 1 – 2 days of therapy. The majority of cases of nausea and vomiting associated with TYGACIL and comparators were either mild or moderate in severity. In patients treated with TYGACIL, nausea incidence was 26% (17% mild, 8% moderate, 1% severe) and vomiting incidence was 18% (11% mild, 6% moderate, 1% severe).
In patients treated for complicated skin and skin structure infections (cSSSI), nausea incidence was 35% for TYGACIL and 9% for vancomycin/aztreonam; vomiting incidence was 20% for TYGACIL and 4% for vancomycin/aztreonam. In patients treated for complicated intra-abdominal infections (cIAI), nausea incidence was 25% for TYGACIL and 21% for imipenem/cilastatin; vomiting incidence was 20% for TYGACIL and 15% for imipenem/cilastatin. In patients treated for community-acquired bacterial pneumonia (CABP), nausea incidence was 24% for TYGACIL and 8% for levofloxacin; vomiting incidence was 16% for TYGACIL and 6% f |
