Summary of safety profile: The total number of cSSTI and cIAI patients treated with tigecycline in Phase 3 and 4 clinical studies was 2,393.
In clinical trials, the most common medicinal product-related treatment emergent adverse reactions were reversible nausea (21 %) and vomiting (13 %), which usually occurred early (on treatment days 1-2) and were generally mild or moderate in severity.
Adverse reactions reported with tigecycline, including clinical trials and post-marketing experience, are tabulated as follows. (See Table 4.)
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Description of selected adverse reactions: Antibiotic class effects: Pseudomembranous colitis which may range in severity from mild to life threatening Overgrowth of non-susceptible organisms, including fungi.
Tetracycline class effects: Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Tetracycline class adverse reactions may include photosensitivity, pseudotumour cerebri, pancreatitis, and antianabolic action which has led to increased BUN, azotaemia, acidosis, and hyperphosphataemia.
Tigecycline may be associated with permanent tooth discolouration if used during tooth development.
In Phase 3 and 4 cSSTI and cIAl clinical studies, infection-related serious adverse reactions were more frequently reported for subjects treated with tigecycline (7.1 %) vs comparators (5.3 %). Significant differences in sepsis/septic shock with tigecycline (2.2 %) vs comparators (1.1 %) were observed.
AST and ALT abnormalities in tigecycline treated patients were reported more frequently in the post therapy period than in those in comparator-treated patients, which occurred more often on therapy.
In all Phase 3 and 4 (cSSTI and cIAl) studies, death occurred in 2.4 % (54/2216) of patients receiving tigecycline and 1.7% (37/2206) of patients receiving active comparators.
Paediatric population: Very limited safety data were available from two PK studies. No new or unexpected safety concerns were observed with tigecycline in these studies.
In an open-label, single ascending dose PK study, the safety of tigecycline was investigated in 25 children aged 8 to 16 years who recently recovered from infections. The adverse reaction profile of tigecycline in these 25 subjects was generally consistent with that in adults.
The safety of tigecycline was also investigated in an open-label, ascending multi-dose PK study in 58 children aged 8 to 11 years with cSSTI (n=15), cIAI (n=24) or community acquired pneumonia (n=19). The adverse reaction profile of tigecycline in these 58 subjects was generally consistent with that in adults, with the exception of nausea (48.3 %), vomiting (46.6 %) and elevated lipase in serum (6.9 %) which were seen at greater frequencies in children than in adults.