|The FDA has issued new information about this safety issue, see the FDA Drug Safety Communication issued 09-27-2013.|
[09-01-2010] The U.S. Food and Drug Administration (FDA) is reminding healthcare professionals of an increased mortality risk associated with the use of the intravenous antibacterial Tygacil (tigecycline) compared to that of other drugs used to treat a variety of serious infections. 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 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.
See the Data Summary Section for details.
- 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.
- Report adverse events involving Tygacil to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.
The pooled analysis grouped 13 trials with patients given Tygacil for both approved and unapproved indications by type of infection (see Table below), comparing the overall mortality for Tygacil vs. pooled control agents. Overall, in the trials, death occurred in 4.0% (150/3788) of patients receiving Tygacil and 3.0% (110/3646) of 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% (95% CI 0.1, 1.2) between Tygacil and comparator treated patients. Results are shown in the following table:
|Infection Type||Tygacil deaths/total patients (%)||Comparator Antibiotics deaths/total patients (%)||Risk Difference* (95% Confidence Interval)|
|cSSSI||12/834 (1.4%)||6/813 (0.7%)||0.7 (-0.3, 1.7)|
|cIAI||42/1382 (3.0%)||31/1393 (2.2%)||0.8 (-0.4, 2.0)|
|CAP||12/424 (2.8%)||11/422 (2.6%)||0.2 (-2.0, 2.4)|
|HAP||66/467 (14.1%)||57/467 (12.2%)||1.9 (-2.4, 6.3)|
|Non-VAP†||41/336 (12.2%)||42/345 (12.2%)||0.0 (-4.9, 4.9)|
|VAP†||25/131 (19.1%)||15/122 (12.3%)||6.8 (-2.1, 15.7)|
|RP||11/128 (8.6%)||2/43 (4.7%)||3.9 (-4.0, 11.9)|
|DFI||7/553 (1.3%)||3/508 (0.6%)||0.7 (-0.5, 1.8)|
|Overall Adjusted||150/3788 (4.0%)||110/3646 (3.0%)||0.6 (0.1, 1.2) **|
cSSSI = Complicated skin and skin structure infection; cIAI = Complicated intra-abdominal infections; CAP = Community-acquired pneumonia; HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia; RP = Resistant pathogens; DFI = Diabetic foot infection.
*Risk Difference = the difference between the percentage of patients who died in the Tygacil and comparator antibiotic groups. The 95% CI for each infection type was calculated using the normal approximation method without continuity correction.
† Subgroups of the HAP population
** Overall adjusted (random effects model by trial weight) risk difference estimate
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.