The Food and Drug Administration is adding a boxed warning about the increased mortality associated with the use of intravenous tigecycline for both approved and unapproved indications, the agency announced on Sept. 27.
The addition of the warning is based on the FDA’s analysis of data from 10 clinical studies of tigecycline for approved uses – complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), and community-acquired bacterial pneumonia – that showed an increased risk of death among those treated with tigecycline, compared with other antibacterial drugs. The analysis was performed after the FDA issued a drug safety communication about the warning in September 2010.
Tigecycline, a tetracycline-class antibacterial drug marketed as Tygacil by Pfizer, was approved in 2005.
In the statement, the FDA advised health care professionals to "reserve Tygacil for use in situations when alternative treatments are not suitable." The boxed warning says that the cause of the increased morality risk "has not been established."
In the 10 studies of tigecycline for the approved indications, which included studies conducted since it was approved, the mortality rate was 2.5% among those treated with tigecycline vs. 1.8% among those treated with other antimicrobial drugs. The adjusted difference in the mortality risk was 0.6%.
"In general, the deaths resulted from worsening infections, complications of infection, or other underlying medical conditions," the FDA statement said.
The 2010 safety announcement was based on a meta-analysis of 13 phase III and IV studies that found a 4% mortality rate among patients treated with tigecycline vs. 3% among those treated with other antibacterial drugs, for an adjusted risk difference of 0.6%. In that analysis, the greatest increase in mortality risk occurred in patients with ventilator-associated pneumonia, but the risk also increased in patients with cSSSIs, cIAIs, and diabetic foot infections. The drug is not approved for hospital-acquired pneumonia, including ventilator-associated pneumonia, or for diabetic foot infections.
To view the revised label, click here. Serious adverse events associated with tigecycline should be reported to the FDA at 800-332-1088 or via MedWatch.