FDA Issues Tigecycline Safety Alert

Alternatives to tigecycline "should be considered" when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen "most clearly" in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non-ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is "often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection," the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.

Alternatives to tigecycline "should be considered" when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen "most clearly" in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non-ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is "often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection," the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.

Alternatives to tigecycline "should be considered" when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen "most clearly" in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non-ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is "often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection," the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.