An increase in all-cause mortality has been observed across phase 3 and 4 clinical studies in Tygacil-treated patients versus comparator. In a pooled analysis of all 13 phase 3 and 4 trials that included a comparator, death occurred in 4% (150/3788) of patients receiving tigecycline and 3% (110/3646) of patients receiving comparator drugs resulting in an unadjusted risk difference of 0.9% (95% CI 0.1, 1.8). In a pooled analysis of these trials, based on a random effects model by trial weight, an adjusted risk difference of all-cause mortality was 0.6% (95% CI 0.1, 1.2) between tigecycline and comparator-treated patients. The cause of this increase has not been established. This increase should be considered when selecting among treatment options.
Anaphylaxis/anaphylactoid reactions have been reported in nearly all antibacterial agents, including tigecycline, and may be life-threatening.
Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Therefore, Tygacil should be administered with caution in patients with known hypersensitivity to tetracycline class antibiotics. Due to the structural similarities of glycylcycline class antibiotics to tetracycline class antibiotics, similar adverse effects may include: Photosensitivity, pseudotumor cerebri, pancreatitis, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia).
Tygacil may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking tigecycline, the patient should be apprised of the potential hazard to the fetus. Results of animal studies indicate that tigecycline crosses the placenta and is found in fetal tissues. Decreased fetal weights in rats and rabbits (with associated delays in ossification) and fetal loss in rabbits have been observed with tigecycline. (See Use in pregnancy under Precautions.)
The use of Tygacil during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). Results of studies in rats with Tygacil have shown bone discoloration. Tygacil should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated.
Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of any antibacterial agent.
Treatment with antibacterial agents alters the flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is the primary cause of "antibiotic-associated colitis". After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis.