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 (tigecycline) . TYGACIL (tigecycline) 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.

Table 1. Incidence (%) of Adverse Reactions Through Test of Cure Reported in ≥ 2% of Patients Treated in Clinical Studies

In all 13 Phase 3 and 4 trials that included a comparator, death occurred in 4.0% (150/3788) of patients receiving TYGACIL (tigecycline) 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 (tigecycline) 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.

Table 2. Patients with Outcome of Death bv Infection Tvne

In comparative clinical studies, infection-related serious adverse events were more frequently reported for subjects treated with TYGACIL (tigecycline) (7%) versus comparators (6%). Serious adverse events of sepsis/septic shock were more frequently reported for subjects treated with TYGACIL (tigecycline) (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].

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 (tigecycline) and comparators were either mild or moderate in severity. In patients treated with TYGACIL (tigecycline) , 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 (tigecycline) and 9% for vancomycin/aztreonam; vomiting incidence was 20% for TYGACIL (tigecycline) and 4% for vancomycin/aztreonam. In patients treated for complicated intra-abdominal infections (cIAI), nausea incidence was 25% for TYGACIL (tigecycline) and 21% for imipenem/cilastatin; vomiting incidence was 20% for TYGACIL (tigecycline) and 15% for imipenem/cilastatin. In patients treated for community-acquired bacterial pneumonia (CABP), nausea incidence was 24% for TYGACIL (tigecycline) and 8% for levofloxacin; vomiting incidence was 16% for TYGACIL (tigecycline) 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 (tigecycline) 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, hyponatremia

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 postapproval use of TYGACIL (tigecycline) . 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

Read the Tygacil (tigecycline) Side Effects Center for a complete guide to possible side effects »

Warfarin

Prothrombin time or other suitable anticoagulation test should be monitored if tigecycline is administered with warfarin [see CLINICAL PHARMACOLOGY].

Oral Contraceptives

Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective.

Last reviewed on RxList: 8/5/2010
This monograph has been modified to include the generic and brand name in many instances.