Tigecare Special Precautions

All-Cause Mortality: An increase in all-cause mortality has been observed in a meta-analysis of Phase 3 and 4 clinical trials in Tigecycline-treated patients versus comparator-treated patients. In all 13 Phase 3 and 4 trials that included a comparator, death occurred in 4.0% (150/3788) of patients receiving Tigecycline and 3.0% (110/3646) of patients receiving comparator drugs. In a pooled analysis of these trials, based on a random effects model by trial weight, the adjusted risk difference of all-cause mortality was 0.6% (95% CI 0.1, 1.2) between Tigecycline and comparator-treated patients. An analysis of mortality in all trials conducted for approved indications (cSSSI, cIAI, and CABP), including post-market trials showed an adjusted mortality rate of 2.5% (66/2640) for tigecycline and 1.8% (48/2628) for comparator, respectively. The adjusted risk difference for mortality stratified by trial weight was 0.6% (95% CI 0.0, 1.2). The cause of this mortality difference has not been established. Generally, deaths were the result of worsening infection, complications of infection or underlying co-morbidities. Tigecycline for Injection should be reserved for use in situations when alternative treatments are not suitable [see Indications and Adverse Reactions].
Mortality Imbalance and Lower Cure Rates in Hospital-Acquired Pneumonia: A trial of patients with hospital acquired, including ventilator-associated, pneumonia failed to demonstrate the efficacy of Tigecycline. In this trial, patients were randomized to receive TIGECYCLINE (100 mg initially, then 50 mg every 12 hours) or a comparator. In addition, patients were allowed to receive specified adjunctive therapies. The sub-group of patients with ventilator-associated pneumonia who received Tigecycline had lower cure rates (47.9% versus 70.1% for the clinically evaluable population). In this trial, greater mortality was seen in patients with ventilator-associated pneumonia who received Tigecycline (25/131 [19.1%] versus 15/122 [12.3%] in comparator-treated patients). Particularly high mortality was seen among Tigecycline-treated patients with ventilator-associated pneumonia and bacteremia at baseline (9/18 [50.0%] versus 1/13 [7.7%] in comparator-treated patients).
Anaphylactic Reactions: Anaphylactic reactions have been reported with nearly all antibacterial agents, including Tigecycline, and may be life-threatening. Tigecycline is structurally similar to tetracycline-class antibacterial drugs and should be avoided in patients with known hypersensitivity to tetracycline-class antibacterial drugs.
Hepatic Adverse Effects: Increases in total bilirubin concentration, prothrombin time and transaminases have been seen in patients treated with tigecycline. Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline. Some of these patients were receiving multiple concomitant medications.
Patients who develop abnormal liver function tests during tigecycline therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing tigecycline therapy. Hepatic dysfunction may occur after the drug has been discontinued.
Pancreatitis: Acute pancreatitis, including fatal cases, has occurred in association with tigecycline treatment. The diagnosis of acute pancreatitis should be considered in patients taking tigecycline who develop clinical symptoms, signs, or laboratory abnormalities suggestive of acute pancreatitis. Cases have been reported in patients without known risk factors for pancreatitis. Patients usually improve after tigecycline discontinuation. Consideration should be given to the cessation of the treatment with tigecycline in cases suspected of having developed pancreatitis [see Adverse Reactions].
Tooth Discoloration and Enamel Hypoplasia: The use of Tigecycline 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). This adverse reaction is more common during long-term use of tetracyclines, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Advise the patient of the potential risk to the fetus if Tigecycline is used during the second or third trimester of pregnancy.
Inhibition of Bone Growth: The use of Tigecycline during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the tetracycline was discontinued. Advise the patient of the potential risk to the fetus if Tigecycline is used during the second or third trimester of pregnancy.
Clostridioides difficile-Associated Diarrhea: Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Tigecycline, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Sepsis/Septic Shock in Patients with Intestinal Perforation: Monotherapy with tigecycline should be avoided in patients with complicated intra-abdominal infections (cIAI) secondary to clinically apparent intestinal perforation. In cIAI studies (n=1642), 6 patients treated with Tigecycline, and 2 patients treated with imipenem/cilastatin presented with intestinal perforations and developed sepsis/septic shock. The 6 patients treated with Tigecycline had higher APACHE II scores (median=13) versus the 2 patients treated with imipenem/cilastatin (APACHE II scores=4 and 6). Due to differences in baseline APACHE II scores between treatment groups and small overall numbers, the relationship of this outcome to treatment cannot be established.
Tetracycline-Class Adverse Effects: Tigecycline is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia).
Development of Drug-Resistant Bacteria: Prescribing Tigecycline for Injection in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.