Tigecycline adverse reactions

# Adverse Reactions

## Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical trials, 2514 patients were treated with TYGACIL. TYGACIL was discontinued due to adverse reactions in 7% of patients compared to 6% for all comparators. Table 1 shows the incidence of treatment-emergent adverse reactions through test of cure reported in 2% of patients in these trials.
In all 13 Phase 3 and 4 trials that included a comparator, death occurred in 4.0% (150/3788) of patients receiving TYGACIL and 3.0% (110/3646) of patients receiving comparator drugs. In a pooled analysis of these trials, based on a random effects model by trial weight, an adjusted risk difference of all-cause mortality was 0.6% (95% CI 0.1, 1.2) between TYGACIL and comparator-treated patients (see Table 2). The cause of the imbalance has not been established. Generally, deaths were the result of worsening infection, complications of infection or underlying co-morbidities.
An analysis of mortality in all trials conducted for approved indications - cSSSI, cIAI, and CABP, including post-market trials (315, 400, 900) - showed an adjusted mortality rate of 2.5% (66/2640) for tigecycline and 1.8% (48/2628) for comparator, respectively. The adjusted risk difference for mortality stratified by trial weight was 0.6% (95% CI 0.0, 1.2).
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 .
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% for levofloxacin.
Discontinuation from tigecycline was most frequently associated with nausea (1%) and vomiting (1%). For comparators, discontinuation was most frequently associated with nausea (<1%).
The following adverse reactions were reported infrequently (<2%) in patients receiving TYGACIL in clinical studies:
Body as a Whole: injection site inflammation, injection site pain, injection site reaction, septic shock, allergic reaction, chills, injection site edema, injection site phlebitis
Cardiovascular System: thrombophlebitis
Digestive System: anorexia, jaundice, abnormal stools
Metabolic/Nutritional System: increased creatinine, hypocalcemia, hypoglycemia
Special Senses: taste perversion
Hemic and Lymphatic System: partial thromboplastin time (aPTT), prolonged prothrombin time (PT), eosinophilia, increased international normalized ratio (INR), thrombocytopenia
Skin and Appendages: pruritus
Urogenital System: vaginal moniliasis, vaginitis, leukorrhea

## Post-Marketing Experience
The following adverse reactions have been identified during post-approval use of TYGACIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.
- anaphylaxis/anaphylactoid reactions
- acute pancreatitis
- hepatic cholestasis, and jaundice
- severe skin reactions, including Stevens-Johnson Syndrome*symptomatic hypoglycemia in patients with and without diabetes mellitus