Tygacil

Generic name: Tigecycline for injection

Trade name: Zetan

Full names: Tigecycline for injection, Zetan, tigecycline, Taige, Tigecycline for Injection

Indications:

This product is suitable for the treatment of infections caused by sensitive strains of specific bacteria in patients over 18 years old under the following circumstances:

Complicated skin and soft tissue infections - Escherichia coli, Enterococcus faecalis (limited to vancomycin-susceptible strains), Staphylococcus aureus (methicillin-susceptible and resistant strains), Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius and S. constellatus), Streptococcus pyogenes and Bacteroides fragilis.

Complicated intra-abdominal infections - Citrobacter fraudii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (limited to vancomycin-susceptible strains), Staphylococcus aureus (limited to methicillin-susceptible strains), Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides monomorpha, Bacteroides vulgaris, Clostridium perfringens and Peptostreptococcus parvum.

Dosage:

The recommended dosage regimen of tigecycline is 100 mg as an initial dose, then 50 mg every 12 hours. Tigecycline should be administered as an intravenous infusion (IV) every 12 hours for approximately 30 to 60 minutes.

The recommended course of treatment for this product is 5 to 14 days for the treatment of complicated skin and soft tissue infections or complicated intra-abdominal infections. The duration of treatment should be based on the severity and location of the infection, and the patient's clinical and bacteriological progress.

Adverse reactions:

The most common side effect is nausea and vomiting, which usually occurs on the first 1-2 days of treatment.

Uncommon side effects include edema, phlebitis, thrombophlebitis, anorexia, abnormal bowel movements, increased creatinine levels, elevated transaminases, hypocalcemia, hypoglycemia, hyponatremia, abnormal taste, prolonged prothrombin time, eosinophilia, thrombocytopenia, vaginal candidiasis, vaginitis, etc.

Contraindications:

Contraindicated in patients with known hypersensitivity to tigecycline.

Patients allergic to tetracycline antibiotics may be allergic to tigecycline.

Notes:

All-cause mortality: A meta-analysis of phase III and phase IV clinical studies found that compared with the control drug group, subjects in the tigecycline group had an increased all-cause mortality. In all 13 Phase III and IV clinical studies with control groups, the mortality rate was 4.0% (150/3788) in subjects receiving tigecycline and 3.0% (110/3646) in the control group. In a pooled analysis of these studies, the adjusted risk difference in all-cause mortality between tigecycline and comparator was 0.6% (95% CI 0.1, 1.2) based on a random-effects model stratified by study weight. Analysis of mortality across all studies (including postmarketing studies) conducted in the approved indications (cSSSI, cIAI, and CABP) showed adjusted mortality rates of 2.5% (66/2640) in the tigecycline group and 1.8% (48/2628) in the comparator group. The adjusted mortality risk difference stratified by study weight was 0.6% (95% CI 0.0,1.2). The reason for this difference in mortality is unknown. This increase in all-cause mortality should be taken into consideration when selecting therapeutic agents. Overall, deaths were due to exacerbation of infection, complications of infection, or underlying comorbidities. Tigecycline should continue to be used clinically only when no suitable alternative therapy is available.

In clinical studies of complicated skin and soft tissue infections (cSSSI), complicated intra-abdominal infections (cIAI), diabetic foot infections, hospital-acquired pneumonia, and studies of drug-resistant pathogens, numerically higher mortality rates were observed in patients treated with tigecycline than in control treatments. The reasons for these results remain unknown, but it cannot be ruled out that the efficacy and safety are worse than those of the comparator.

Uneven mortality and lower cure rates in hospital-acquired pneumonia.

Allergic reactions: Allergic reactions have been reported with almost all antibacterial drugs, including tigecycline, and can be life-threatening. Tigecycline is structurally similar to tetracycline antibiotics; therefore, tigecycline should be avoided in patients allergic to tetracycline antibiotics.

Hepatic Reactions: Cases of liver injury, primarily cholestatic, including some cases of fatal hepatic failure, have been reported in patients receiving tigecycline. Increases in total bilirubin concentration, prothrombin time, and transaminases have been observed in patients receiving tigecycline. Severe liver dysfunction and liver failure have been reported in individual cases. Some of these patients also received multiple concomitant medications. Although hepatic failure that occurs in tigecycline-treated patients may be due to underlying conditions or concomitant medications, the possible role of tigecycline in these events should be considered. Patients receiving tigecycline who have abnormal liver function tests should be monitored to prevent further deterioration of liver function and to evaluate the risks and benefits of tigecycline therapy. Hepatic dysfunction may occur after discontinuation of the drug.

Pancreatitis: Acute pancreatitis, including fatal cases, has been reported in association with tigecycline administration. A diagnosis of acute pancreatitis should be considered in patients taking tigecycline who develop clinical symptoms, indications, or abnormal laboratory test indicators suggestive of acute pancreatitis. The vast majority of reported cases occurred after at least 1 week of treatment. Cases have been reported in patients with no known risk factors for pancreatitis. Patients usually improve after discontinuing tigecycline. Discontinuation of tigecycline therapy should be considered in patients with suspected pancreatitis.

Fetal damage: Pregnant women may suffer fetal harm when using this product. If a patient becomes pregnant while taking tigecycline, the patient should be informed of the potential hazard to the fetus. Animal studies suggest that tigecycline can cross the placenta and be found in fetal tissue. Tigecycline can cause weight loss in fetal rats and rabbits (combined with corresponding delayed ossification) and stillbirth in rabbits.

Tooth discoloration: Studies with tigecycline in rats showed bone discoloration. Use of this product during tooth development (second half of pregnancy, infancy, and children under 8 years of age) can cause permanent tooth discoloration (yellow-gray-brown). Tigecycline can cause bone discoloration in studies in rats. Therefore, this product should not be used during tooth development unless other medications are ineffective or contraindicated.

Clostridium difficile-associated diarrhea: Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibiotics, including tigecycline. Severity ranges from mild diarrhea to fatal colitis. Antibiotic treatment can alter the normal intestinal flora, leading to overgrowth of Clostridium difficile. Clostridium difficile produces toxins A and B, which contribute to the development of CDAD. Highly toxin-producing strains of C. difficile result in increased morbidity and mortality, and these infections are often refractory to antibiotic treatment and may require colectomy. CDAD should be considered in patients who develop diarrhea after receiving antibiotics. Because CDAD has been reported to occur more than two months after the use of antibiotics, the medical history should be carefully understood. If CDAD is suspected or confirmed, antibiotics currently being used that do not directly inhibit C. difficile should be discontinued. Replace fluids, electrolytes, and protein appropriately, treat C. difficile with antibiotics, and perform surgical evaluation as clinically indicated.

Storage:

Before preparation, this product should be stored at 20~25℃, with an allowable deviation of 15~30℃. This product can be stored at room temperature for up to 24 hours after reconstitution (up to 6 hours if the bottle is stored in an infusion bottle or intravenous infusion bag at room temperature after reconstitution). Accordingly, this product should be immediately mixed with 0.9% Sodium Chloride Injection (USP) or 5% Glucose Injection (USP) after reconstitution and stored under refrigerated conditions at 2 to 8°C for 48 hours. After reconstitution, this product should be immediately transferred and diluted with an intravenous solution for intravenous infusion.

Mechanism of action:

Tigecycline is a glycylcycline antibacterial drug that inhibits bacterial protein synthesis by binding to the 30S subunit of the ribosome and preventing aminoacylated tRNA molecules from entering the A site of the ribosome. This prevents the peptide chain from being elongated by incorporating amino acid residues. Tigecycline contains a glycyl amino group substituted at position 9 of minocycline. This substitution is not found in any natural or semisynthetic tetracyclines and gives tigecycline unique microbiological properties. Tigecycline is not affected by the two major resistance mechanisms of tetracyclines (ribosomal protection and efflux mechanisms). Accordingly, in vitro and in vivo experiments confirmed that tigecycline has broad-spectrum antibacterial activity. Cross-resistance between tigecycline and other antibiotics has not been found. Tigecycline is not affected by resistance mechanisms such as beta-lactamases (including extended-spectrum beta-lactamases), target site modifications, macrolide efflux pumps, or enzyme target site changes (such as gyrase/topoisomerase). In vitro studies have not demonstrated antagonism between tigecycline and other commonly used antibacterial drugs. Generally speaking, tigecycline is a bacteriostatic agent.

Safety and efficacy:

Retrospectively analyze the use of tigecycline in patients in chest hospitals, in order to provide a theoretical basis for the rational use of anti-infective drugs. Methods: The medical records of 52 inpatients who received tigecycline from January 2016 to January 2018 were extracted, and the clinical rational use and off-label use of tigecycline were analyzed from aspects such as management indicators, medication indications, medication process and medication results. Results: Among patients using tigecycline, they were mainly concentrated in the intensive care unit (ICU), and the main reason for taking the drug was pulmonary infection. The proportion of patients with consultation records reached 88.46% (target value 100%); the rate of compliance with off-label medication standards was 84.62% (target value 90%), of which mainly off-label and overdose medication. 48 cases (92.31%) underwent etiological examination, and 84.62% had drug susceptibility test results. The drug utilization index (DUI) value of 52 patients was 1.082. Conclusion: The total effective rate of tigecycline clinical treatment is 59.62%, and off-label drug use is common.