Tigacil, 50 mg, lyophilisate for solution for infusion, 10 pcs.

Tigacil, 50 mg, lyophilisate for solution for infusion, 10 pcs.

To reduce the development of resistance and ensure the effectiveness of therapy, it is necessary to use Tigacil® only for the treatment of infectious diseases caused by microorganisms sensitive to the drug.

To select and adjust antibacterial therapy, if possible, microbiological identification of the pathogen should be carried out and its sensitivity to tigecycline should be determined. Tigacil® can be used for empirical antibacterial monotherapy pending the results of microbiological tests.

Antibiotics belonging to the glycylcycline class are structurally similar to antibiotics from the tetracycline class. Tigacil® may cause adverse reactions similar to those seen with tetracycline class antibiotics. Such reactions may include increased photosensitivity, intracranial hypertension, pancreatitis and anti-anabolic effects leading to increased blood urea nitrogen, azotemia, acidosis and hypophosphatemia. The use of Tigacil® in patients with known hypersensitivity to tetracycline antibiotics is contraindicated.

Anaphylactic/anaphylactoid reactions, including anaphylactic shock, are observed with the use of almost all antibacterial agents, including Tigacil®.

Patients who experience changes in liver test results during treatment with Tigacil® should be observed to promptly identify signs of liver dysfunction (single cases of significant liver dysfunction and liver failure have been reported) and assess the benefit-risk ratio of continuing therapy with Tigacil®. Adverse reactions may develop after therapy has been completed.

The effectiveness and safety of Tigacil® in patients with hospital-acquired pneumonia has not been confirmed by the results of clinical studies.

Pseudomembranous colitis of varying severity is observed when taking almost all antibacterial drugs, including Tigacil®. The possibility of such a diagnosis should be considered if diarrhea occurs during or after completion of treatment. Clostridium difficile associated diarrhea is suspected

, or confirmation of this diagnosis, it may be necessary to stop using antibiotics other than those prescribed to treat
Clostridium difficile
.

When prescribing Tigacil® to patients with complicated intra-abdominal infections due to intestinal perforation, or patients with incipient sepsis or septic shock, the advisability of using combination antibacterial therapy should be considered.

The use of Tigacil®, like any other antibiotic, can promote excessive growth of non-susceptible microorganisms, including fungi. Patients should be closely monitored during treatment. When superinfection is diagnosed, appropriate measures should be taken.

The effect of cholestasis on the pharmacokinetics of tigecycline has not been established. Excretion in bile accounts for approximately 50% of the total excretion of tigecycline. Therefore, patients with cholestasis should be under medical supervision.

Experience with the use of Tigacil® for the treatment of infections in patients with severe concomitant diseases is limited.

The use of the drug Tigacil® during the formation of teeth can lead to a permanent change in the color of the teeth to yellow, gray, or brown.

There are reports of the development of acute pancreatitis during the use of the drug Tigacil®, in some cases with a fatal outcome. Caution should be exercised when using the drug Tigacil® in patients with suspected acute pancreatitis (clinical symptoms or corresponding changes in laboratory parameters). There are known cases of the development of acute pancreatitis in patients who did not have risk factors for the development of this disease. Typically, symptoms of pancreatitis disappear after discontinuation of the drug. It is necessary to consider the possibility of drug withdrawal in patients with symptoms of pancreatitis.

In a prospective analysis of clinical trial results, there was a slight increase in overall mortality (ie, death from any cause) in the group of patients receiving tigecycline compared with the group of patients receiving comparators. Therefore, Tigacil® should be used only in cases where alternative therapy is not available.

Use in children

Data on the use of Tigacil® in children are limited. Therefore, the use of the drug is recommended in situations where alternative antibiotic therapy is not available.

Nausea and vomiting are the most common adverse reactions in children and adolescents. Particular attention should be paid to the risk of dehydration.

Abdominal pain is a common side effect in children as well as in adults. It should be borne in mind that pain in the abdominal area may be associated with the development of pancreatitis. If pancreatitis develops, tigecycline therapy should be discontinued.

Liver function tests, blood coagulation parameters, hematological parameters, and amylase and lipase concentrations should be monitored before starting tigecycline therapy and regularly during therapy.

Tigecycline should not be used in children under the age of 8 years due to a lack of data on the effectiveness and safety of the drug in this group, as well as due to changes in tooth color (see section “Method of administration and dosage” and “Side effects”).

Impact on the ability to drive vehicles and machinery

Studies of the effect of tigecycline on the ability to drive vehicles and operate machines have not been conducted. Patients receiving tigecycline may experience dizziness, which may affect the ability to drive and use machines.

Instructions for use TYGACIL

To reduce the development of resistance and ensure the effectiveness of therapy, it is necessary to use tigecycline only for the treatment and prevention of infectious diseases caused by microorganisms sensitive to the drug. To select and adjust antibacterial therapy, if possible, microbiological identification of the pathogen should be carried out and its sensitivity to tigecycline should be determined. Tigecycline can be used for empirical antibacterial monotherapy pending the results of microbiological tests.

In clinical trials using tigecycline for the treatment of complicated skin and soft tissue infections, complicated intra-abdominal infections, diabetic foot infections, community-acquired pneumonia, and studies to determine activity against pathogen resistance, there was a slight increase in all-cause mortality in the tigecycline group compared with comparators. In a pooled analysis of 13 phase 3 and 4 clinical trials, overall mortality rates were 4% (150/3788) in the tigecycline group and 3% (110/3646) in the comparator group. The difference in unadjusted risk was 0.9% (95% CI 0.1, 1.8). In an overall analysis of study data based on a random-effects model with weights for each study, the difference in adjusted risk was 0.6% (95% CI 0.1, 1.2) between the tigecycline and comparator groups. The reason for the differences is unknown, but lower efficacy and safety compared to comparators cannot be ruled out. It is recommended to take this into account when choosing antibiotic therapy.

Patients with superinfections, particularly hospital-acquired (nosocomial) pneumonia, had worse clinical outcomes. If, after starting tigecycline therapy, it is determined that the site of infection is not in the skin and soft tissues, or not intra-abdominal, then another therapy with proven effectiveness should be considered. Patients should be closely monitored during treatment. If superinfection occurs, appropriate measures should be taken.

The use of tigecycline for unapproved indications is not recommended.

Anaphylactic/anaphylactoid reactions, incl. anaphylactic shock is observed with the use of almost all antibacterial agents, including tigecycline.

Cases of liver dysfunction, mainly cholestatic, have been reported, incl. about the development of liver failure with a fatal outcome. Although liver dysfunction occurred mainly in patients with severe underlying diseases and in patients taking concomitant medications, the possible contribution of tigecycline to the development of such disorders cannot be excluded. Patients who experience changes in liver test results during tigecycline treatment should be monitored for early signs of liver dysfunction and to assess the benefit-risk ratio of continuing tigecycline therapy. Adverse reactions may develop after therapy has been completed.

Antibiotics belonging to the glycylcycline class are structurally similar to antibiotics from the tetracycline class. Tigecycline may cause adverse reactions similar to those seen with tetracycline class of antibiotics. Such reactions may include increased photosensitivity, intracranial hypertension, pancreatitis and anti-anabolic effects leading to increased blood urea nitrogen, azotemia, acidosis and hyperphosphatemia. Therefore, tigecycline should be used with caution in patients with known sensitivity to tetracycline antibiotics.

There are reports of the development of acute pancreatitis while taking tigecycline, in some cases with a fatal outcome. Caution should be exercised when using tigecycline in patients with suspected acute pancreatitis (clinical symptoms or corresponding changes in laboratory parameters). There are known cases of the development of acute pancreatitis in patients who did not have risk factors for the development of this disease. Typically, symptoms of pancreatitis disappear after discontinuation of the drug. It is necessary to consider the possibility of drug withdrawal in patients with symptoms of pancreatitis.

Experience with tigecycline for the treatment of infections in patients with severe underlying medical conditions is limited.

In clinical trials of tigecycline for the treatment of complicated skin and soft tissue infections, the most common type of infection in patients taking tigecycline was cellulitis (59%), followed by large abscesses (27.5%). Patients with severe underlying illness, such as those caused by immunosuppression, patients with pressure ulcers, or patients with infections requiring treatment lasting more than 14 days (eg, necrotizing fasciitis) were not included in the studies. The studies included a limited number of patients with comorbidities such as diabetes (20%), peripheral vascular disease (7%), intravenous drug use (2%), and HIV infection (1%). There is also limited experience with tigecycline for the treatment of infections with associated bacteremia (3%). Due to limited data, caution should be exercised when treating these patients. Results from large studies of patients with infections associated with diabetic foot syndrome showed that tigecycline was less effective than the comparator drug, therefore, the use of tigecycline in such cases is not recommended.

In clinical trials of tigecycline for the treatment of complicated intra-abdominal infections, the most common type of infection in patients taking tigecycline was appendicitis (51%), followed by complicated cholecystitis (14%), intra-abdominal abscess (10%), and intestinal perforation (10%). ) and perforation of the stomach or duodenum in less than 24 hours (5%). 76% of these patients also had concomitant diffuse peritonitis (detected surgically). The study included a limited number of patients with severe underlying disease, such as those caused by immunosuppression, and patients with an APACHE II score >15 (4%) or surgically detectable multiple intra-abdominal abscesses (10%). There is also limited experience with tigecycline for the treatment of infections with associated bacteremia (6%). Due to limited data, caution should be exercised when treating these patients.

When prescribing tigecycline to patients with complicated intra-abdominal infections due to intestinal perforation, or patients with incipient sepsis or septic shock, the advisability of using combination antibacterial therapy should be considered.

The effect of cholestasis on the pharmacokinetics of tigecycline has not been established. Excretion in bile accounts for approximately 50% of the total excretion of tigecycline. Therefore, patients with cholestasis should be under medical supervision.

Because tigecycline may prolong both PT/INR and APTT, close monitoring of appropriate coagulation test results is necessary when tigecycline is used concomitantly with anticoagulants.

The development of pseudomembranous colitis of varying severity has been noted when taking almost all antibacterial drugs, including tigecycline. It is necessary to consider the possibility of such a diagnosis in the case.

The use of tigecycline, like any other antibiotic, can promote excessive growth of non-susceptible microorganisms, including fungi. Patients should be closely monitored during treatment.

Results from a study using tigecycline in rats revealed the development of bone discoloration. The use of tigecycline during the formation of teeth can lead to discoloration of teeth to yellow, gray, or brown. Tigacil should not be used during tooth development unless other drugs are ineffective or contraindicated.

The efficacy and safety of tigecycline in the treatment of community-acquired pneumonia was studied in adults in two randomized, double-blind, actively controlled international multicenter studies.

The effectiveness and safety of tigecycline in patients with hospital-acquired (nosocomial) pneumonia has not been confirmed by the results of clinical studies.

Impact on the ability to drive vehicles and operate machinery

Studies of the effect of tigecycline on the ability to drive vehicles and operate machines have not been conducted. Patients receiving tigecycline may experience dizziness, which may affect the ability to drive and use machines.

Antimicrobial drugs are one of the most dynamically developing groups of medicines. One of the stimulating factors is the phenomenon of acquired resistance of microorganisms to drugs. Due to the progressive increase in the number of multidrug-resistant strains of pathogens, recommendations for antimicrobial pharmacotherapy even five to seven years ago require a critical attitude.

Currently, two principal directions for the development of original antimicrobial agents can be distinguished: drugs active against multidrug-resistant gram-negative flora, and drugs directed against multidrug-resistant gram-positive flora.

Despite the obvious need and clinical relevance, the development of new anti-gram-negative antibiotics is proceeding very slowly. This is partly due to antibiotic resistance mechanisms common among non-fermenting Gram-negative rods. These microorganisms maintain their viability in an environment containing antimicrobial agents through the production of betalactamases, including metallobetalactamases, activation of the efflux system (active removal of the drug that has penetrated the cell), and disruption of the permeability of the cell membrane. That is, life support systems are multidirectional and complement each other, which dramatically increases the stability of the entire cell as a whole.

The problem of multidrug-resistant Gram-positive infection has been of little relevance for a long time. Resistance of Staphylococcus spp. to antibacterial agents is associated with the production of betalactamases [1, 2]. With the spread of staphylococcal strains resistant to natural penicillins, semisynthetic and then antistaphylococcal cephalosporins (I-II generations) began to be used. In this situation, drugs from other pharmacological groups, sometimes more toxic, but possessing almost absolute antistaphylococcal activity, found themselves deprived of their niche in clinical practice. Thus, the glycopeptide vancomycin, discovered back in the 1950s, became truly in demand only in the 1980s.

It is also worth paying attention to Enterococcus spp., which has an unusual spectrum of sensitivity to antibacterial drugs. It is believed that among the “old” antibiotics, enterococcus has natural sensitivity only to aminopenicillins and glycopeptides [1, 2].

The emergence of vancomycin-resistant strains of Staphylococcus spp. and Enterococcus spp. (VRSA and VRE) stimulated the development of new antibacterial agents. New developments include linezolid (Zyvox) and tigecycline (Tigatsil). Linezolid is currently the only drug from the oxazolidinone group that is active against most known gram-positive microorganisms, including those resistant to glycopeptides.

Tigecycline is a representative of a new class of glycylcycline antibacterial drugs. It has a wide spectrum of activity against aerobic and anaerobic gram-positive and gram-negative microorganisms. Tigecycline is active against multi-resistant microorganisms such as MRSA, VRE, enterobacteriaceae producing extended spectrum beta-lactamases, most species of Acinetobacter spp. Tigecycline also has activity against intracellular bacteria and anaerobes. Tigecycline is not active against Pseudomonas aeruginosa. Also, some members of the family Enterobacteriacea, such as Proteus spp., have reduced sensitivity to tigecycline [3, 4].

Clinical efficacy of Tigecycline

The clinical effectiveness of tigecycline has been studied in several large studies.

Efficacy of tigecycline in the treatment of complicated intra-abdominal infections [5]

Two international, multicenter, randomized, double-blind, phase 3 studies examined the efficacy and safety of tigecycline compared with imipenem/cilastatin in adult patients with intra-abdominal infections. Both studies were performed on a total of 1642 patients with intra-abdominal abscesses that developed after surgery and previous antibiotic therapy. The studies included patients with perforated or gangrenous appendicitis, diverticulitis, cholecystitis, empyema of the appendix, gallbladder, and purulent peritonitis.

Patients were randomized to receive tigecycline (first dose 100 mg, then 50 mg every 12 hours) or to receive imipenem/cilastatin (500/500 mg every 6 hours, dose adjusted based on glomerular filtration rate). The duration of treatment ranged from 5 to 14 days.

The end point of the studies was the clinical response to therapy (cure or lack thereof), and microbiological effectiveness was additionally monitored.

As a result, in the group receiving tigecycline, cure or remission was achieved in 86.1% of patients, in the group receiving imipenem/cilastatin in 86.2% of patients. No statistically significant differences were found. The overall microbiological effectiveness of the studied drugs was also comparable. The researchers concluded that tigecycline has high clinical and microbiological efficacy comparable to carbapenems in the treatment of complicated intra-abdominal infections in adults.

The effectiveness of tigecycline as monotherapy for complicated skin and soft tissue infections [6]

Two international, multicenter, randomized, double-blind, controlled phase 3 studies compared the efficacy and safety of tigecycline with the combination of vancomycin + aztreonam for 5-14 days. It was important to select a comparator drug or combination of drugs that would replicate the activity spectrum of tigecycline as closely as possible and would be available in different countries around the world. Vancomycin is highly active against gram-positive microorganisms, and aztreonam is one of the drugs of choice for gram-negative infections.

The study included adult patients with complicated skin and soft tissue infections, including wound infections, infected ulcers and burns.

1116 patients were randomized to receive tigecycline (first dose 100 mg, then 50 mg every 12 hours) or vancomycin (1 mg every 12 hours) in combination with aztreonam (2 g every 12 hours), for 14 days .

As a result, clinical efficacy in the group receiving tigecycline was 79.7%; and in the group receiving comparison drugs 81.9%. Microbiological efficacy was 82.1% with tigecycline and 86.2% with combination therapy including vancomycin and aztreonam. No statistically significant differences were obtained. It was concluded that tigecycline is highly effective in monotherapy of complicated skin and soft tissue infections, comparable to the combination of vancomycin and aztreonam.

Efficacy of tigecycline in the treatment of community-acquired pneumonia [7]

Two international, multicenter, randomized, double-blind, phase 3 studies compared the efficacy and safety of tigecycline and levofloxacin in the treatment of hospitalized patients with community-acquired pneumonia. Tigecycline was compared with levofloxacin, since the latter is one of the drugs of choice in the treatment of community-acquired pneumonia.

859 patients were randomized to receive tigecycline (first dose 100 mg, then 50 mg every 12 hours) or levofloxacin (500 mg every 24 hours or every 12 hours). The duration of therapy was 7-14 days.

As a result, it was noted that tigecycline and levofloxacin showed high clinical efficacy in the treatment of pneumonia in previously healthy individuals: 89.7% and 86.3%, respectively. However, no statistically significant differences were found.

Safety of tigecycline

An important limiting factor when prescribing any pharmacological drug is its toxicity. The safety of tigecycline was assessed in all studies that examined its effectiveness.

Thus, in a study of tigecycline compared with imipenem/cilastatin in the treatment of complicated intra-abdominal infections [5], the most common adverse events were nausea (24.4% vs 19% in the comparison group, p = 0.01), nausea (19.2% vs 14.% on imipenem/cilastatin, p = 0.008) and diarrhea (13.8% vs 13.2% on imipenem/cilastatin, p > 0.05).

In a study of tigecycline compared with vancomycin and aztreonam in the treatment of complicated skin and soft tissue infections [6], patients receiving tigecycline were more likely to experience dyspeptic disorders (46% vs 21% in the comparison group, p < 0.001), such as nausea, vomiting , diarrhea, etc., mostly mild to moderate. Patients receiving vancomycin in combination with aztreonam were significantly more likely to experience skin rashes (19.3% vs 10.6% on tigecycline, p < 0.001) and reactions associated with the cardiovascular system (14.7% vs 8.8% on tigecycline, p = 0.008). In the group receiving tigecycline, there were no changes in general or biochemical blood tests. The number of patients who discontinued therapy due to the development of adverse reactions was higher in the group receiving vancomycin and aztreonam than in the group receiving tigecycline.

In a study of tigecycline versus levofloxacin in the treatment of community-acquired pneumonia [7], patients receiving tigecycline were also more likely to have dyspeptic disorders, whereas patients receiving levofloxacin were more likely to have elevated liver enzymes. The rate of discontinuation of therapy due to the development of adverse reactions was the same in both groups (6.1% vs 8.1%).

These data allow us to conclude that tigecycline has a favorable safety profile. The most common adverse events are more unpleasant than dangerous. There were no statistically significant differences in the frequency of therapy discontinuation due to the development of side effects in the groups receiving tigecycline and comparator drugs.

An important aspect of the safety of tigecycline is the possibility of its use in patients with renal failure without dose adjustment. The pharmacological profile of tigecycline allows it to be prescribed to patients with concomitant diseases that require the use of various medications, because has a low potential for drug interactions [4].

Conclusion

Tigecycline is a drug with a very broad spectrum of antimicrobial activity. Particularly interesting and relevant is its activity against multidrug-resistant pathogens, the role of which is steadily growing every year. Its place in clinical practice is determined by the possibility of use in the treatment of complicated infections of the skin and soft tissues, complicated intra-abdominal infections, community-acquired pneumonia in complex patients at risk of resistant flora, and the presence of various concomitant diseases. The drug is easy to dose (initial dose 100 mg, then 50 mg 2 times a day) and easy to use. ?

Key words: antibacterial therapy, tigecycline.

Keywords: antibacterial therapy, tigecycline.

Literature:

1. Rational antimicrobial pharmacotherapy. Edited by Yakovlev V.P. and Yakovleva S.V. Moscow. Litterra. 2003. 1002 p.
2. Practical guide to anti-infective chemotherapy. Edited by Strachunsky L.S., Belousov Yu.B., Kozlov S.N. Smolensk MACMAH. 2007. 464 p.
3. Instructions for medical use of the drug tigecycline.
4. James E. Frampton and Monique P. Curran. Tigecycline. Drugs 2005; 65 (18): 2623-2635.
5. Babinchak T., Ellis-Grosse E. et al. The Efficacy and Safety of Tigecycline for the Treatment of Complicated Intra-Abdominal Infections: Analysis of Pooled Clinical Trial Data. Clinical Infectious Diseases 2005; 41: S. 354-67.
6. Ellis-Grosse E., Babinchak T., Dartois N. et al. The Efficacy and Safety of Tigecycline in the Treatment of Skin and Skin-Structure Infections: Results of 2 Double-Blind Phase 3 Comparison Studies with Vancomycin-Aztreonam. Clinical Infectious Diseases 2005; 41: S. 341-53.
7. McKeage K. ,Keating G. Tigecycline In Community-Acquired Pneumonia. Drugs 2008; 68 (18): 2633-2644.

Tigacil®

To reduce the development of resistance and ensure the effectiveness of therapy, it is necessary to use Tigacil only for the treatment and prevention of infectious diseases caused by microorganisms sensitive to the drug:

To select and adjust antibacterial therapy, if possible, microbiological identification of the pathogen should be carried out and its sensitivity to tigecycline should be determined. Tigacil can be used for empirical antibacterial monotherapy until the results of microbiological tests are obtained.

Antibiotics belonging to the glycylcycline class are structurally similar to antibiotics from the tetracycline class. Tigacil may cause adverse reactions similar to those seen with tetracycline class antibiotics. Such reactions may include increased photosensitivity, intracranial hypertension, pancreatitis and anti-anabolic effects leading to increased blood urea nitrogen, azotemia, acidosis and hypophosphatemia. Therefore, Tigacil should be used with caution in patients with known sensitivity to tetracycline antibiotics.

Anaphylactic/anaphylactoid reactions, including anaphylactic shock, are observed with the use of almost all antibacterial agents, including Tigacil.

Patients who experience changes in liver test results during treatment with Tigacil should be observed for timely detection of signs of liver dysfunction (single cases of significant liver dysfunction and liver failure have been reported) and to assess the balance of benefits. and the risk of continuing therapy with Tigacil.

Adverse reactions may develop after therapy has been completed.

The effectiveness and safety of Tigacil in patients with hospital-acquired pneumonia has not been confirmed by the results of clinical studies.

Diarrhea of ​​varying severity associated with Clostridium difficile has been observed when taking almost all antibacterial drugs, including Tigacil. The possibility of such a diagnosis should be considered if diarrhea occurs during or after completion of treatment. If Clostridium difficile-associated diarrhea is suspected or confirmed, it may be necessary to discontinue use of antibiotics other than those prescribed to treat Clostridium difficile infection.

When prescribing Tigacil to patients with complicated intra-abdominal infections due to intestinal perforation, or patients with incipient sepsis or septic shock, the advisability of using combination antibacterial therapy should be considered.

The use of Tigacil, like any other antibiotic, can promote excessive growth of non-susceptible microorganisms, including fungi. During treatment, patients should be closely monitored. When superinfection is diagnosed, appropriate measures should be taken.

The effect of cholestasis on the pharmacokinetics of tigecycline has not been established. Excretion in bile accounts for approximately 50% of the total excretion of tigecycline. Therefore, patients with cholestasis should be under medical supervision.

Experience with the use of Tigacil for the treatment of infections in patients with severe concomitant diseases is limited.

The use of Tigacil during the formation of teeth can lead to a change in the color of the teeth to yellow, gray, or brown. Tigacil should not be used during tooth development unless other drugs are ineffective or contraindicated.

There are reports of the development of acute pancreatitis while taking Tigacil, in some cases with a fatal outcome. Caution should be exercised when using Tigacil in patients with suspected acute pancreatitis (clinical symptoms or corresponding changes in laboratory parameters). There are known cases of the development of acute pancreatitis in patients who did not have risk factors for the development of this disease. Typically, symptoms of pancreatitis disappear after discontinuation of the drug. It is necessary to consider the possibility of drug withdrawal in patients with symptoms of pancreatitis.

In clinical studies, an increase in overall mortality was noted compared with comparators. The reasons for the increase in mortality are not clear. It is recommended to take this into account when choosing antibiotic therapy.