Expiration date: 07/2025
Clinical and pharmacological group
(Antibiotic group tetracycline)
Form of issue, composition and packaging
Lyophilizate for preparation of solution for infusion in the form of powder or porous mass of orange.
Excipients: lactose monohydrate, hydrochloric acid q.s to pH, sodium hydroxide q.s to Ph.Bottles of colorless glass with a capacity of 5 ml (10) - packs cardboard.Pharmacological action of anantibiotic group of glycylcyclines, structurally similar to tetracyclines. Inhibits protein translation in bacteria by binding with 30S-ribosomal subunit and blocking the penetration of aminoacyl-tRNA molecules to the ribosomal a-site, which prevents the inclusion of amino acid residues in the growing peptide chains.It is believed that tigecycline has bacteriostatic properties. At 4x the IPC of tigecycline was reduced by two orders of magnitude in the number of colonies Enterococcus spp., Staphylococcus aureus and Escherichia coli.The bactericidal effect of tigecycline was observed in Streptococcus pneumoniae, Haemophilus influenzae and Legionella pneumophila.The mechanism of development of stoichiometrically can overcome the two main mechanisms of microbial resistance observed against tetracycline: ribosomal protection and active excretion. In addition, the activity of tigecycline is not suppressed either by the action of ?-lactamases (including extended spectrum ?-lactamases) or by modification of antibiotic-sensitive areas of the bacterial membrane, nor by the active removal of the antibiotic from the bacterial cell or by modification of the target exposure (eg, hirase/topoisomerase). Thus, tigecycline has a broad spectrum of antibacterial activity. However, tigecycline has no protection against the mechanism of resistance of microorganisms in the form of active removal from the cell, encoded chromosomes Proteeae and Pseudomonas aeruginosa(outflow system MexXY-OprM). There is no cross-resistance between tigecycline and most classes of antibiotics.In General, microorganisms belonging to Proteus spp., Providencia spp. and Morganella spp. less sensitive to tigecycline than other members of Enterobacteriaceae. In addition, some acquired resistance was found in Klebsiella pneumoniae, Enterobacter aerogenes and Enterobacter cloacae. The reduced sensitivity of the representatives of both groups to tigecycline is due to the overexpression of the gene of non-specific active excretion of Asgav, providing resistance to many drugs. Low sensitivity to tigecycline and Acinetobacter baumannii is described.Watch Ekniga lists the control values of the IPC, established by the European working group on testing of sensitivity to antibiotics (EUCAST).
1 flask: tigecycline 50 mg
| Pathogenes | Sensitive | Resistant |
| Staphylococcus spp. | ? 0.5 mg/l | >, 0.5 mg/l |
| Streptococcus spp., ????? S. pneumoniae | ? 0.25 mg/l | >, 0.5 mg/l |
| Enterococcus spp. | ? 0.25 mg/l | >, 0.5 mg/l |
| Enterobacteriaceae | ? 1 mg/l* | >, 2 mg/l |
| Regardless of the type of pathogen | ? 0.25 mg/l | >, 0.5 mg/l |
* Decreased activity of tigecycline in vitro against Proteus spp was noted., Providencia spp. and Morganella spp.For Acinetobacter spp., Streptococcus pneumoniae, other streptococci, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoea and Neisseria meningitidis, no convincing evidence has been obtained for the efficacy of tigecycline.The effectiveness of tigecycline for the treatment of intraabdominal infections caused by anaerobic bacteria, regardless of the parameters of IPC, pharmacokinetic / pharmacodynamic parameters. Therefore, the IPC benchmarks are not presented. It should be noted the wide range of tigecycline IPC for Bacteroides spp. and Clostridium spp. in some cases, exceeding 2 mg/l. There are limited data on the clinical efficacy of tigecycline with enterococcal infections. Nevertheless, a positive reaction to the treatment of polymicrobial intraabdominal infections with tigecycline was shown.The prevalence of acquired resistance in individual species of bacteria may vary depending on time and geographical location.To the drug sensitive gram-positive aerobic micro-organisms: Enterococcus avium, Enterococcus casseliflavus, Enterococcus faecalis1, 2 (including vancomycin-sensitive strains), Enterococcus faecalis (including vancomycin-resistant strains), Enterococcus gallinarum, Staphylococcus aureus1, 2 (including methicillin-sensitive and resistant strains), Staphylococcus epidermidis( including methicillin-sensitive and resistant strains), Staphylococcus haemolyticus, Streptococcus agalactiae1, Streptococcus anginosus1, 2 (including S. anginosus, S. intermedius and S. constellatus), Streptococcus agalactiae1, pyogenes1, Streptococcus pneumoniae3 (penicillin-sensitive strains), Streptococcus pneumoniae (penicillin-resistant strains), Streptococci viridans group, gram-negative aerobic microorganisms: Aeromonas hydrophilia, Citrobacter freundii2, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae2, Escherichia coli1, 2 (including strains producing broad-spectrum beta-lactamase), Haemophilus influenzae3, Haemophilus parainfluenzae, Klebsiella oxytoca2, Klebsiella pneumoniae1, 2 (including strains producing broad-spectrum ?-lactamase) pneumophila3, Moraxella catarrhalis, Serratia marcescens, Bacteroides fragilis group1, 2, Clostridium perfringens2, Peptostreptococcus spp.2, Peptostreptococcus micros, Prevotella spp., atypical microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae.Views, in which the development of acquired resistance is possible: Acinetobacter baumannii, Burkholderia cepacia, Morganella morganii, Providencia spp., Proteus spp., Stenotrophomonas maltophilia.Microorganisms that have their own resistance: Pseudomonas aeruginosa.1, 2, 3 - species for which satisfactory activity has been demonstrated in clinical trials.
Pharmacokinetics
Suction
Because tigecycline administered in/in, it is characterized by 100% oral bioavailability.Distribution of concentrations from 0.1 to 1 µg/ml the binding of tigecycline to in vitro plasma proteins varies from approximately 71% to 89%. In pharmacokinetic studies in animals and humans it is shown that tigecycline is rapidly distributed in tissues.In the human body, the equilibrium VD of tigecycline is 500-700 l (7-9 l/kg), which confirms the extensive distribution of tigecycline outside the plasma and its accumulation in the tissues.Data on the ability of tigecycline to penetrate the BBB in the human body are not available.Cssmax of tigecycline in serum was 866±233 ng / ml with 30-minute infusions and 634±97 ng/ml with 60-minute infusions. AUC0-12 h was $ 2349±850 ng×hour/ml, Metabolism average, less than 20% of tigecycline metabolized. The main substance found in urine and feces was unchanged tigecycline, however glucuronide, N-acetyl metabolite and epimer of tigecycline were also found.Tigecycline does not inhibit metabolism mediated by the following six isoenzymes CYP1A2, ???2?8, CYP2C9, ???2?19, CYP2D6 and CYP3A4. It is neither a competitive inhibitor nor an irreversible cytochrome P450 inhibitor.It was noted that 59% of the prescribed dose is excreted through the intestine (most of the unchanged tigecycline enters the bile), and 33% is excreted by the kidneys. Additional ways of excretion-glucuronidation and excretion of unchanged tigecycline kidneys.Total clearance of tigecycline after the on/in infusion is 24 l/h. renal clearance accounted for approximately 13% of total clearance. Tigecyclin polyexponentially is characterized by the excretion of serum, mean terminal T1/2 of serum after the appointment of repeated doses is 42 h, however, there are considerable individual differences.Pharmacokinetics in special clinical cases of patients with mild impairment of liver function, the pharmacokinetic profile of a single dose of tigecycline does not change. However, in patients with moderate to severe hepatic impairment (class b and C on the child-Pugh scale), the total clearance of tigecycline was reduced by 25% and 55%, and T1/2 increased by 23% and 43%, respectively.In patients with renal insufficiency (CC <, auc 30="" 30="" p="">
Tigecycline pharmacokinetics in elderly patients, in General, did not differ from other age groups.
The pharmacokinetics of tigecycline in patients younger than 18 years has not been studied.
Clinically significant differences of tigecycline clearance in men and women have not been established.
The clearance of tigecycline does not depend on the race.
Clearance, including normalized for body weight, and AUC did not differ significantly among patients with different body mass, including excess of 125 kg in patients weighing more than 125 kg, the value of AUC was 25% lower. Data on patients weighing more than 140 kg are not available.
Dosage
The drug is administered in / in drip for 30-60 min.
The initial dose for adults is 100 mg, then 50 mg every 12 hours.
The course of treatment for complicated infections of the skin and soft tissues, as well as complicated intraabdominal infections is 5-14 days, with community - acquired pneumonia-7-14 days.
The duration of treatment is determined by the severity and localization of infection and the clinical response of the patient to treatment.
Patients with mild to moderate hepatic impairment (classes a and B on the child-Pugh scale) do not require dose adjustment. Patients with severe hepatic impairment (class C child-Pugh) after administration of the initial dose of Tygacil 100 mg, later the drug is prescribed for 25 mg every 12 hours, it is necessary to exercise caution and monitor the patient's response to treatment.
Patients with renal insufficiency and patients undergoing hemodialysis, no dose adjustment is required drug.
Elderly patients do not require dose adjustment.
Rules of preparation and administration of infusion solution
Before use, the contents of each bottle of Tigacil should be dissolved in 0.9% sodium chloride solution, 5% dextrose solution for injection or lactate ringer solution in an amount of 5.3 ml to obtain a finished solution with a concentration of tigecycline 10 mg/ml (5 ml of the finished solution contain 50 mg of tigecycline, each bottle contains an excess of the drug 6%). The bottle is gently rotated until the drug is completely dissolved.
5 ml of the finished solution is transferred into a bottle with a solution for infusion with a capacity of 100 ml (for a dose of 100 mg, take the finished solution from 2 bottles, for a dose of 50 mg - from 1 bottle). The maximum concentration of the final solution for in / infusion should not exceed 1 mg/ml.the Color of the finished solution should be yellow or orange. If the solution is of a different colour or visible inclusions are identified, its use shall not be permitted. The ready solution of Tygacil can be stored at room temperature for up to 24 hours (ready solution in a bottle up to 6 hours, the remaining time - in the form of the final diluted solution). Immediately after dilution of the finished solution, the final solution for infusion can be stored in the refrigerator at a temperature of 2° to 8°C for no more than 48 hours.
Introduction. Tygacil should be entered in/in infusion via a separate system or through a T-shaped catheter. If an IV catheter is used for sequential introduction of several drugs, it must be washed before infusion Tygacil 0.9% solution of sodium chloride, 5% dextrose solution for injection or normal saline and ringer's lactate. During the infusion should take into account the compatibility of tigecycline and other drugs administered through a single catheter.
Overdose
Overdose of the drug Tygacil not described.
In / in the introduction of tigecycline healthy volunteers at a dose of 300 mg at 60-minute duration of the introduction led to increased nausea and vomiting.
Hemodialysis does not provide removal of tigecycline from the body.
Drug interaction
With concomitant use of Tigacil and warfarin (in a single dose of 25 mg), a decrease in clearance of R-warfarin and S-warfarin by 40% and 23%, a decrease in AUC of warfarin by 68% and 29%, respectively. The mechanism of such interaction has not been established so far. Since tigecyclin able to increase the prothrombin time/INR and APTT, using Tygacil simultaneously with anticoagulants is necessary to monitor closely the results of relevant coagulation tests. Warfarin does not alter the pharmacokinetic profile of Tygacil.
Tigecycline is not metabolized by cytochrome P450 isoenzymes. It is therefore expected that active substances that inhibit or induce activity of isoenzymes of cytochrome P450, will not change the clearance of Tygacil. In turn, Tygacil unlikely to influence the metabolism of these groups of drug compounds.
Tygacil at the recommended dose does not affect the speed and extent of absorption or clearance of digoxin (500 micrograms followed by the appointment of a daily dose of 250 mcg). Digoxin does not alter the pharmacokinetic profile of tigecycline. Therefore, when applying Tygacil together with digoxin dose adjustment is not required.
When antibiotics are used simultaneously with oral contraceptives, contraceptive efficacy may decrease.
In in vitro studies, there was no antagonism between tigecycline and other antibiotics belonging to frequently used classes.
Compatibility
Tygacil compatible with 0.9% solution of sodium chloride, 5% dextrose solution for injection or normal saline and ringer's lactate. When you assign through a T-shaped catheter Tygacil dissolved in 0.9% sodium chloride solution or 5% dextrose solution for injection is compatible with amikacin, dobutamine, dopamine hydrochloride, gentamicin, haloperidol, a solution of ringer's lactate, lidocaine hydrochloride, metoclopramide, morphine, norepinephrine, piperacillin/tazobactam (pharmaceutical form, containing EDTA), potassium chloride, propofol, ranitidine hydrochloride, theophylline and tobramycin.
Incompatibility
When applying through a T-shaped catheter Tygacil incompatible with amphotericin b, liposomal amphotericin b, diazepam, esomeprazole and omeprazole.
Pregnancy and lactation
In pregnancy, the use of Tigacil is permissible only in case of extreme necessity, when the benefit to the mother exceeds the possible risk to the fetus.
Data on the excretion of tigecycline with breast milk in humans are lacking. If necessary, the appointment of tigecycline during lactation should stop breastfeeding.
Experience in the use of the drug Tygacil in childbirth is not available.
Side effect
Most often: nausea (26%) and vomiting (18%), which usually occur at the beginning of treatment (1 or 2 day of treatment) and, in most cases, have a mild or moderate course. The reason for discontinuation of therapy Tigallo most often were nausea (1%), and vomiting.
Side effects classification: very often (?1/10), often (? 1/100 to <, 1 10="" 1="" 1000="" 100="" 000="" p="">
From the blood coagulation system: often - the increase in APTT, prothrombin time/MHO.
On the part of the hemopoietic system: sometimes - eosinophilia, and in rare cases - thrombocytopenia.
Allergic reactions: in rare cases-anaphylactic / anaphylactoid reactions.
From the Central nervous system: often-dizziness.
From the side of cardiovascular system: frequently - phlebitis, and sometimes thrombophlebitis.
From the digestive system: very often-nausea, vomiting, diarrhea, often - abdominal pain, dyspepsia, anorexia, sometimes - acute pancreatitis, increased activity of ACT and ALT - in serum, hyperbilirubinemia, sometimes - jaundice, in isolated cases - severe liver dysfunction and liver failure.
Dermatological reactions: often-itching, rash.
From the genital system: sometimes-vaginal candidiasis, vaginitis, leukorrhea.
Local reactions: sometimes-inflammation, pain, swelling and phlebitis at the injection site
Other: often-headache, asthenia, delayed wound healing, sometimes-chills.
On the part of laboratory indicators: often - increased blood urea nitrogen, increased activity of schf in serum, increased activity of amylase in serum, hypoproteinemia, sometimes - increased creatinine in the blood, hypocalcemia, hyponatremia, hypoglycemia.
Storage terms and conditions
The drug should be stored out of reach of children at a temperature not higher than 25°C. shelf life - 1.5 years.
Indications
- complicated skin and soft tissue infections,
- complicated intraabdominal infections,
- community-acquired pneumonia.
Contraindications
- hypersensitivity to the components of the drug,
- hypersensitivity to antibiotics of tetracycline group.
With caution, the drug should be used in severe hepatic insufficiency.
Special instruction
To reduce the development of resistance and to ensure the effectiveness of therapy it is necessary to use Tigacil only for the treatment and prevention of infectious diseases caused by sensitive microorganisms. To select and correct antibacterial therapy, microbiological identification of the pathogen and determine its sensitivity to tigecycline should be carried out if possible. Tygacil can be used for empirical antimicrobial monotherapy before receiving results of microbiological tests.
Antibiotics belonging to the class of glycylcyclines have a structural similarity with antibiotics of tetracycline class. Tygacil can cause adverse reactions similar to the adverse reactions to the antibiotic class of tetracyclines. Such reactions can be increased photosensitivity, intracranial hypertension, pancreatitis and antianabolic action, leading to an increase in the content of urea nitrogen in the blood, nitrogen, acidosis and hypophosphatemia. Therefore, Tygacil should be used with caution in patients with known sensitivity to tetracycline antibiotics.
Anaphylactic/anaphylactoid reactions, including anaphylactic shock, have been observed with use of nearly all antibacterial agents, including Tygacil.
Patients in whom treatment with Tigatron marked changes in results of liver tests, should be observed for early detection of signs of liver dysfunction (registered isolated cases of significant liver dysfunction and liver failure) and assess the balance of benefits and risks of continuing therapy with Tigatron. The development of undesirable reactions is possible after the therapy has been completed.
The efficacy and safety of Tygacil patients with hospital pneumonia was not confirmed by the results of clinical studies.
Diarrhea associated with Clostridium difficile, noted at the time of acceptance of almost all antibacterial drugs, including Tygacil. At suspicion of diarrhea associated with Clostridium difficile or confirmation of the diagnosis may require stopping the use of antibiotics, except those that are prescribed to treat infections caused by Clostridium difficile.
When using tigecycline may develop pseudomembranous colitis of varying severity. It is necessary to consider the possibility of such a diagnosis in the event of diarrhea during or after treatment.
When you assign Tygacil patients with complicated intra-abdominal infections due to perforation of the bowel, or patients with incipient sepsis or septic shock, be sure to consider the expediency of combined antibiotic therapy.
The use of Tygacil, like any other antibiotic, may contribute to excessive growth of insensitive microorganisms, including fungi. During treatment, patients should be closely monitored. Appropriate measures should be taken to diagnose superinfection.
The effect of cholesterol on the pharmacokinetics of tigecycline has not been established. Excretion with bile is approximately 50% of the total excretion of tigecycline. Therefore, patients with cholestasis should be under the supervision of a doctor.
Experience with the use of Tygacil for the treatment of infections in patients with concomitant diseases of severe limited.
The use of Tygacil during the period of tooth formation may cause tooth discoloration to yellow, gray, brown. Tygacil should not be used during the development of the teeth except when other drugs are ineffective or contraindicated.
Use in Pediatrics
The efficacy and safety of the drug in children and adolescents under the age of 18 years is not established.
Influence on the ability to drive vehicles and management mechanisms
Studies of the influence of tigecycline on the ability to manage transport and work with mechanisms were not carried out. In patients receiving tigecycline may dizziness, which may affect the ability to drive and operate machinery.
Application in violation of liver function
Patients with mild to moderate hepatic impairment (classes a and B on the child-Pugh scale) do not require dose adjustment. Patients with severe hepatic impairment (class C child-Pugh) after administration of the initial dose of Tygacil 100 mg, later the drug is prescribed for 25 mg every 12 hours, it is necessary to exercise caution and monitor the patient's response to treatment.
