Tigecycline

TYGACIL is a tetracycline class antibacterial indicated in patients 18 years of age and older for: • Complicated skin and skin structure infections. • Complicated intra-abdominal infections. • Community-acquired bacterial pneumonia. Limitations of Use: TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia. To reduce the development of drug-resistant bacteria and maintain the effectiveness of TYGACIL and other antibacterial drugs, TYGACIL should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.

Tigecycline is a tetracycline class antibacterial. Mechanism of Action Tigecycline inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. In general, tigecycline is considered bacteriostatic, however, TYGACIL has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila.

• Initial dose of 100 mg followed by 50 mg every 12 hours administered intravenously over approximately 30 to 60 minutes. • Severe hepatic impairment (Child Pugh C): Initial dose of 100 mg followed by 25 mg every 12 hours. • Obtain baseline blood coagulation parameters, including fibrinogen, and continue to monitor regularly during treatment with TYGACIL.

TYGACIL is contraindicated for use in patients who have known hypersensitivity to tigecycline or to any of the excipients. Reactions have included anaphylactic reactions. • Known hypersensitivity to tigecycline.

Boxed warning (all-cause mortality): An increase in all-cause mortality has been observed in a meta-analysis of Phase 3 and 4 clinical trials in TYGACIL-treated patients versus comparator. The cause of this mortality risk difference of 0.6% (95% CI 0.1, 1.2) has not been established. TYGACIL should be reserved for use in situations when alternative treatments are not suitable. • All-Cause Mortality: A meta-analysis of Phase 3 and 4 clinical trials demonstrated an increase in all-cause mortality in TYGACIL-treated patients compared to controls with a risk difference of 0.6% (95% CI 0.1, 1.2). The cause of this increase has not been established. An increase was also seen in a meta-analysis limited to the approved indications [0.6% (95% CI 0.0, 1.2)]. The greatest difference in mortality was seen in TYGACIL-treated patients with ventilator-associated pneumonia.

The following serious adverse reactions are described elsewhere in the labeling: • All-Cause Mortality • Mortality Imbalance and Lower Cure Rates in Hospital-Acquired Pneumonia • Anaphylaxis [ Warning and Precautions ] • Hepatic Adverse Effects [ Warnings and Precautions ] • Pancreatitis [ Warnings and Precautions ] The most common adverse reactions (incidence >5%) are nausea, vomiting, diarrhea, abdominal pain, headache, and increased SGPT.

• Warfarin: Suitable anticoagulation test should be monitored if TYGACIL is administered to patients receiving warfarin. • Calcineurin Inhibitors: Serum concentrations of calcineurin inhibitors (e.g., tacrolimus, cyclosporine) should be monitored during treatment with TYGACIL due to risk of toxicity.

Prior to reconstitution, TYGACIL should be stored at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F). The reconstituted solution of TYGACIL may be stored at room temperature (not to exceed 25°C/77°F) for up to 24 hours (up to 6 hours in the vial and the remaining time in the intravenous bag).