In clinical studies in complicated skin and skin structure infections (cSSTI), complicated intra-abdominal infections (cIAI), diabetic foot infections, nosocomial pneumonia and studies in resistant pathogens, a numerically higher mortality rate among tigecycline treated patients has been observed as compared to the comparator treatment. The causes of these findings remain unknown, but poorer efficacy and safety than the study comparators cannot be ruled out.
Superinfection: In clinical trials in cIAI patients, impaired healing of the surgical wound has been associated with superinfection. A patient developing impaired healing should be monitored for the detection of superinfection.
Patients who develop superinfections, in particular nosocomial pneumonia, appear to be associated with poorer outcomes. Patients should be closely monitored for the development of superinfection. If a focus of infection other than cSSTI or cIAI is identified after initiation of tigecycline therapy consideration should be given to instituting alternative antibacterial therapy that has been demonstrated to be efficacious in the treatment of the specific type of infection(s) present.
Anaphylaxis: Anaphylaxis/anaphylactoid reactions, potentially life-threatening, have been reported with tigecycline.
Hepatic failure: Cases of liver injury with a predominantly cholestatic pattern have been reported in patients receiving tigecycline treatment, including some cases of hepatic failure with a fatal outcome. Although hepatic failure may occur in patients treated with tigecycline due to the underlying conditions or concomitant medicinal products, a possible contribution of tigecycline should be considered.
Tetracycline class antibiotics: Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Tigecycline may have adverse reactions similar to tetracycline class antibiotics. Such reactions may include photosensitivity, pseudotumor cerebri, pancreatitis, and anti-anabolic action which has led to increased BUN, azotaemia, acidosis, and hyperphosphataemia.
Pancreatitis: Acute pancreatitis, which can be serious, has occurred (frequency: uncommon) 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. Most of the reported cases developed after at least one week of treatment. 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.
Underlying diseases: Experience in the use of tigecycline for treatment of infections in patients with severe underlying diseases is limited.
In clinical trials in cSSTI, the most common type of infection in tigecycline treated-patients was cellulitis (58.6 %), followed by major abscesses (24.9 %). Patients with severe underlying disease, such as those that were immunocompromised, patients with decubitus ulcer infections, or patients that had infections requiring longer than 14 days of treatment (for example, necrotizing fasciitis), were not enrolled. A limited number of patients were enolled with co-morbid factors such as diabetes (25.8 %), peripheral vascular disease (10.4 %), intravenous substance abuse (4.0 %), and HIV-positive infection (1.2 %). Limited experience is also available in treating patients with concurrent bacteraemia (3.4 %). Therefore, caution is advised when treating such patients. The results in a large study in patients with diabetic foot infection, showed that tigecycline was less effective than comparator, therefore, tigecycline is not recommended for use in these patients.
In clinical trials in cIAI, the most common type of infection in tigecycline-treated patients was complicated appendicitis (50.3 %), followed by other diagnoses less commonly reported such as complicated cholecystitis (9.6 %), perforation of intestine (9.6 %), intra-abdominal abscess (8.7 %), gastric or duodenal ulcer perforation (8.3 %), peritonitis (6.2 %) and complicated diverticulitis (6.0 %). Of these patients, 77.8 % had surgically-apparent peritonitis. There were a limited number of patients with severe underlying disease such as immunocompromised patients, patients with APACHE II scores > 15 (3.3 %), or with surgically apparent multiple intra-abdominal abscesses (11.4 %). Limited experience is also available in treating patients with concurrent bacteraemia (5.6 %). Therefore, caution is advised when treating such patients.
Consideration should be given to the use of combination antibacterial therapy whenever tigecycline is to be administered to severely ill patients with cIAI secondary to clinically apparent intestinal perforation or patients with incipient sepsis or septic shock.
The effect of cholestasis in the pharmacokinetics of tigecycline has not been properly established. Biliary excretion accounts for approximately 50 % of the total tigecycline excretion. Therefore, patients presenting with cholestasis should be closely monitored.
Prothrombin time or other suitable anticoagulation test should be used to monitor patients if tigecycline is administered with anticoagulants.
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 diarrhoea during or subsequent to the administration of any antibacterial agent.
The use of tigecycline may result in overgrowth of non-susceptible organisms, including fungi. Patients should be carefully monitored during therapy.
Results of studies in rats with tigecycline have shown bone discolouration. Tigecycline may be associated with permanent tooth discolouration in humans if used during tooth development.
Fertility: Tigecycline did not affect mating or fertility in rats at exposures up to 4.7 times the human daily dose based on AUC. In female rats, there were no compound-related effects on ovaries or oestrus cycles at exposures up to 4.7 times the human daily dose based on AUC.
Effects on ability to drive and use machines: Dizziness may occur and this may have an effect on driving and use of machines.
Use in Children: Clinical experience in the use of tigecycline for the treatment of infections in paediatric patients aged 8 years and older is very limited. Consequently, use in children should be restricted to those clinical situations where no alternative antibacterial therapy is available.
Nausea and vomiting are very common adverse reactions in children and adolescents. Attention should be paid to possible dehydration. Tigecycline should be preferably administered over a 60-minute length of infusion in paediatric patients.
Abdominal pain is commonly reported in children as it is in adults. Abdominal pain may be indicative of pancreatitis. If pancreatitis develops, treatment with tigecycline should be discontinued.
Liver function tests, coagulation parameters, haematology parameters, amylase and lipase should be monitored prior to treatment initiation with tigecycline and regularly while on treatment.
Tigecycline should not be used in children under 8 years of age due to the lack of safety and efficacy data in this age group and because tigecycline may be associated with permanent teeth discolouration.