The FDA issued a drug safety alert reminding health care professionals that compared to other drugs used to treat serious infections, the intravenous antibacterial drug Tygacil carries increased risk for some.
The increased risk was determined using a pooled analysis of clinical trials. The cause of the excess death in these trials is often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection.
The increased risk was seen most clearly in patients treated for hospital-acquired pneumonia, especially ventilator-associated pneumonia, but was also seen in patients with complicated skin and skin structure infections, complicated intra-abdominal infections and diabetic foot infections. Tygacil (tigecycline) is not approved for the treatment of hospital-acquired pneumonia (including ventilator-associated pneumonia) or diabetic foot infection. Tygacil is approved by FDA for the treatment of complicated skin and skin structure infections, complicated intra-abdominal infections and community acquired pneumonia.
FDA has updated the Warnings and Precautions and Adverse Reactions sections of the Tygacil drug label to include information regarding increased mortality risk of Tygacil. Healthcare professionals have also been informed of this increased risk via a Dear Health Care Professional letter.
The pooled analysis grouped 13 trials with patients given Tygacil for both approved and unapproved indications by type of infection comparing the overall mortality for Tygacil versus pooled control agents. Overall, in the trials, death occurred in 4.0 percent or 150 out of 3788 patients receiving Tygacil and 3.0 percent or 110 out of 3646 patients receiving comparator antibiotics. An adjusted risk difference for all-cause mortality based on a random effects model stratified by trial weight was 0.6 percent between Tygacil and comparator treated patients. Results of this analysis are shown in a table in the Drug Safety Communication on FDA's website at www.fda.gov/Drugs/.
Although for each indication, the mortality difference was not statistically significant, mortality in Tygacil treated patients was numerically greater in every infection, sometimes considerably greater, particularly in ventilator-associated pneumonia. Tygacil is not approved for ventilator associated pneumonia because of an unacceptably low cure rate, as well as excess mortality.
As stated in the package insert, in general, Tygacil is considered bacteriostatic; however, it has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila. One possible reason for the mortality difference is that in certain severe infections, Tygacil's bacteriostatic mechanism may put it at some disadvantage, although for approved indications, cure rates with Tygacil were generally similar to that seen with the bactericidal active control agents.
At this time, FDA recommends that Healthcare Professionals be aware that:
- The greatest increase in risk of death with Tygacil was seen in patients with ventilator-associated pneumonia, an unapproved use.
- Alternatives to Tygacil should be considered in patients with severe infections.
- Adverse events involving Tygacil can be reported to the FDA MedWatch program at www.fda.gov/medwatch.
The FDA is committed to keeping healthcare professionals informed of the latest safety information. If you have questions about this safety communication, you can reach us at: [email protected].