Overview
11 DESCRIPTION Tigecycline for Injection, USP is a tetracycline class antibacterial for intravenous infusion. The chemical name of tigecycline is (4 S ,4a S ,5a R ,12a S )- 9-[2-( tert -butylamino)acetamido]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2 naphthacenecarboxamide. The molecular formula is C 29 H 39 N 5 O 8 and the molecular weight is 585.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tigecycline is a tetracycline class antibacterial [see Microbiology ( 12.4 )] . 12.2 Pharmacodynamics Cardiac Electrophysiology No significant effect of a single intravenous dose of tigecycline for injection 50 mg or 200 mg on QTc interval was detected in a randomized, placebo-and active-controlled four-arm crossover thorough QTc study of 46 healthy subjects. 12.3 Pharmacokinetics The mean pharmacokinetic parameters of tigecycline after single and multiple intravenous doses based on pooled data from clinical pharmacology studies are summarized in Table 3 . Intravenous infusions of tigecycline were administered over approximately 30 to 60 minutes. Table 3.
Indications
- 1 INDICATIONS AND USAGE Tigecycline for injection is a tetracycline class antibacterial indicated in patients 18 years of age and older for: Complicated skin and skin structure infections ( 1.1 ) Complicated intra-abdominal infections ( 1.2 ) Community-acquired bacterial pneumonia ( 1.3 ) Limitations of Use: Tigecycline for injection is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia ( 1.4 ).
Common Doses
- 100 mg
- 50 mg
- 25 mg
- 1.2 mg
Dosage
2 DOSAGE AND ADMINISTRATION Initial dose of 100 mg, followed by 50 mg every 12 hours administered intravenously over approximately 30 to 60 minutes. (2.1) Severe hepatic impairment (Child Pugh C): Initial dose of 100 mg followed by 25 mg every 12 hours. ( 2.2 ) Obtain baseline blood coagulation parameters, including fibrinogen, and continue to monitor regularly during treatment with tigecyclineetracycline. ( 2.4 , 5.6 ) 2.1 Recommended Adult Dosage The recommended dosage regimen for tigecycline for injection is an initial dose of 100 mg, followed by 50 mg every 12 hours.
Black Box Warning
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 tigecycline-treated patients versus comparator. The cause of this mortality risk difference of 0.6% (95% CI 0.1, 1.2) has not been established. Tigecycline for injection should be reserved for use in situations when alternative treatments are not suitable [see Indications and Usage ( 1.4 ), Warnings and Precautions (5.1, 5.2) and Adverse Reactions (6.1)]. WARNING: ALL-CAUSE MORTALITY See full prescribing information for complete boxed warning.
Contraindications
- 4 CONTRAINDICATIONS Tigecycline for injection is contraindicated for use in patients who have known hypersensitivity to tigecycline or to any of the excipients. Reactions have included anaphylactic reactions [ see Warnings and Precautions ( 5.3 ) and Adverse Reactions ( 6.2 ) ] . Known hypersensitivity to tigecycline. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: All-Cause Mortality [see Boxed Warning and Warnings and Precautions ( 5.1 )] Mortality Imbalance and Lower Cure Rates in Hospital-Acquired Pneumonia [see Warnings and Precautions ( 5.2 )] Anaphylaxis [Warning and Precautions ( 5.3 )] Hepatic Adverse Effects [Warnings and Precautions ( 5.4 )] Pancreatitis [Warnings and Precautions ( 5.5 )] The most common adverse reactions (incidence >5%) are nausea, vomiting, diarrhea, abdominal pain, headache, and increased SGPT. ( 6.
Interactions
- 7 DRUG INTERACTIONS Warfarin: Suitable anticoagulation test should be monitored if tigecycline for injection is administered to patients receiving warfarin. ( 7.1 ) Calcineurin Inhibitors: Serum concentrations of calcineurin inhibitors (e.g., tacrolimus, cyclosporine) should be monitored during treatment with tigecycline for injection due to risk of toxicity. ( 7.2 ) 7.1 Warfarin Prothrombin time or other suitable anticoagulation test should be monitored if tigecycline is administered with warfarin [see Clinical Pharmacology ( 12.3 )] . 7.