Tygacil (tigecycline)Company: Wyeth
Approval Status: Approved 2005
Treatment for: complicated skin and skin structure and intra-abdominal infections and bacterial pneumonia
Areas: Dermatology / Plastic Surgery; Gastrointestinal; Immune System; Respiratory
Tygacil (tigecycline) is a tetracycline-class antibacterial indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms.
Tygacil is specifically indicated for the following conditions:
Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis.
Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros
Community-acquired bacterial pneumonia caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (betalactamase negative isolates), and Legionella pneumophila.
Tygacil is supplied as a lyophilized powder for reconstitution to intravenous infusions. The recommended initial dose is 100 mg, followed by 50 mg every 12 hours. Intravenous infusions of Tygacil should be administered over approximately 30 to 60 minutes every 12 hours.
Duration of treatment
The recommended duration of treatment with Tygacil for complicated skin and skin structure infections or for complicated intra-abdominal infections is 5 to 14 days. The recommended duration of treatment with Tygacil for community-acquired bacterial pneumonia is 7 to 14 days. The duration of therapy should be guided by the severity and site of the infection and the patient's clinical and bacteriological progress.
The FDA approval of Tygacil for complicated skin and skin structure infections was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (Studies 300 and 305). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with vancomycin (1 g intravenous every 12 hours)/aztreonam (2 g intravenous every 12 hours) for 5 to 14 days. The primary efficacy endpoint was the clinical response at the test of cure visit (5-14 days after therapy) in the co-primary populations of the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) patients. The clinical cure rates (% of cured) were as follows:
Study 300: CE population: 82.9% for Tygacil; 82.3% for Vancomycin/Aztreonam. c-mITT population: 75.5% for Tygacil; 76.9% for Vancomycin/Aztreonam.
Study 305: CE population: 89.7% for Tygacil; 94.4% for Vancomycin/Aztreonam. c-mITT population: 84.3% for Tygacil; 86.9% for Vancomycin/Aztreonam.
The FDA approval of Tygacil for complicated intra-abdominal infections was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (Studies 301 and 306). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with imipenem/cilastatin (500 mg intravenous every 6 hours) for 5 to 14 days. The primary efficacy endpoint was the clinical response (% responding) at the test-of-cure visit for the microbiologically evaluable (ME) and the microbiologic modified intent-to-treat (m-mITT) co-primary populations. Study 301 ME: 80.6% vs. imipenem/cilastatin: 82.4%; m-mITT: 73.5% vs. imipenem/cilastatin: 78.2%. Study 306 ME: 91.3% vs. imipenem/cilastatin: 89.9%; m-mITT: 86.6% vs. imipenem/cilastatin: 84.6%.
The FDA approval of Tygacil for community-acquired pneumonia was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (Studies 308 and 313). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with levofloxacin (500 mg intravenous every 12 or 24 hours). In Study 308, after at least 3 days of intravenous therapy, a switch to oral levofloxacin (500 mg daily) was permitted for both treatment arms. Total therapy was 7 to 14 days. The primary endpoint was clinical response at the test of cure (TOC) visit in the co-primary populations of the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT). The clinical cure rates (% of cured) were as follows:
Study 308: CE population: 90.6% for Tygacil; 87.2% for Levofloxacin c-mITT population: 78% for Tygacil; 77.8% for Levofloxacin
Study 313: CE population: 88.9% for Tygacil; 85.3% for Levofloxacinc-mITT population: 83.7% for Tygacil; 81.5% for Levofloxacin.
Adverse events associated with the use of Tygacil may include, but are not limited to, the following:
- Abdominal pain
Mechanism of Action
Tyhacil 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. Tigecycline carries a glycylamido moiety attached to the 9-position of minocycline. The substitution pattern is not present in any naturally occurring or semisynthetic tetracycline and imparts certain microbiologic properties to tigecycline. In general, tigecycline is considered bacteriostatic; however, it has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila.
Tanaseanu C, Milutinovic S, Calistru PI, Strausz J, Zolubas M, Chernyak V, Dartois N, Castaing N, Gandjini H, Cooper CA; 313 Study Group Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia. BMC Pulmonary Medicine 2009 Sep 9;9:44
Fomin P, Koalov S, Cooper A, Babinchak T, Dartois N, De Vane N, Castaing N, Tellado J; 301 And 306 Study Groups The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections - the European experience. Journal of Chemotherapy 2008 Oct;20 Suppl 1:12-9
Bergallo C, Jasovich A, Teglia O, Oliva ME, Lentnek A, de Wouters L, Zlocowski JC, Dukart G, Cooper A, Mallick R; 308 Study Group Safety and efficacy of intravenous tigecycline in treatment of community-acquired pneumonia: results from a double-blind randomized phase 3 comparison study with levofloxacin. Diagnostic Microbiology and Infectious Disease 2009 Jan;63(1):52-61
Vasilev K, Reshedko G, Orasan R, Sanchez M, Teras J, Babinchak T, Dukart G, Cooper A, Dartois N, Gandjini H, Orrico R, Ellis-Grosse E; 309 Study Group A Phase 3, open-label, non-comparative study of tigecycline in the treatment of patients with selected serious infections due to resistant Gram-negative organisms including Enterobacter species, Acinetobacter baumannii and Klebsiella pneumoniae. The Journal of Antimicrobial Chemotherapy 2008 Sep;62 Suppl 1:i29-40
Florescu I, Beuran M, Dimov R, Razbadauskas A, Bochan M, Fichev G, Dukart G, Babinchak T, Cooper CA, Ellis-Grosse EJ, Dartois N, Gandjini H; 307 Study Group Efficacy and safety of tigecycline compared with vancomycin or linezolid for treatment of serious infections with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: a Phase 3, multicentre, double-blind, randomized study. The Journal of Antimicrobial Chemotherapy 2008 Sep;62 Suppl 1:i17-28
Postier RG, Green SL, Klein SR, Ellis-Grosse EJ, Loh E; Tigecycline 200 Study Group Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients. Clinical Therapeutics 2004 May;26(5):704-14
For additional information regarding Tygacil or complicated skin and skin structure and intra-abdominal infections and bacterial pneumonia, please visit the Tygacil web page.
Tygacil Drug Information
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