The US Food and Drug Administration (FDA) approved today a new boxed warning, the strongest warning given to a drug, for intravenous tigecycline (Tygacil; Pfizer), a tetracycline-class antibacterial drug. Tigecycline, first approved in 2005, is used for treating complicated skin infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults.
In 2010, the FDA issued a drug safety communication showing, in a meta-analysis of 13 trials, an increased risk of death among patients receiving tigecycline compared with other antibacterial drugs (4.0% vs 3.0% with an adjusted risk difference of 0.6%). The increased risk was greatest in patients with ventilator-associated pneumonia, a use for which the FDA has not approved the drug. Increased risk of death was also seen in patients with complicated skin infections, complicated intra-abdominal infections, and diabetic foot infections—another complication for which the drug has not been approved.
After the 2010 communication, the FDA analyzed data from 10 clinical trials involving tigecycline and only agency-approved uses. Again, analysis showed a higher risk of death among patients receiving tigecycline compared with other antibacterial drugs (2.5% vs 1.8% with an adjusted risk difference of 0.6%). These deaths, in general, resulted from worsening infections, complications of infection, or other underlying medical conditions, but the FDA said the cause of this mortality risk difference has not been established.
The FDA wrote that health care professionals should reserve tigecycline for use in situations when alternative treatments are not suitable. In the prescribing label, the FDA said tigecycline should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. Such bacteria include Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Klebsiella pneumoniae, and Legionella pneumophila.