Tigacil lyophilisate for preparing solution for infusion vials 50mg 10 pcs
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Active ingredients
Tigecyclin
Release form
Lyophilisate
Composition
1 bottle contains: Tigecyclin 50 mg Auxiliary substances: lactose monohydrate - 100 mg, hydrochloric acid - q.sub to pH, sodium hydroxide - q.sup to pH.
Pharmacological effect
The antibiotic of the glycylcycline group is structurally similar to tetracyclines. Inhibits protein translation in bacteria by binding to the 30S-subunit of the ribosome and blocking the penetration of aminoacyl-tRNA molecules onto the ribosome A-site, which prevents the incorporation of amino acid residues into the growing peptide chains. Tigecycline is believed to have bacteriostatic properties. At 4-fold IPC of tigecycline, a decrease of two orders of the number of colonies of Enterococcus spp., Staphylococcus aureus and Escherichia coli was observed. The bactericidal effect of tigecycline was observed in relation to Streptococcus pneumoniae, Haemophilus influenzae and Legionella pneumophila. against tetracyclines: ribosomal protection and active elimination. In addition, tigecycline activity is not inhibited either by the action of β-lactamase (including extended-spectrum β-lactamase), by modification of antibiotic-sensitive areas of the bacterial membrane, or by actively removing the antibiotic from the bacterial cell or by modifying the target of exposure (eg, gyrase / topoisomerase). Thus, tigecyclin has a broad spectrum of antibacterial activity. However, tigecycline lacks protection against the mechanism of resistance of microorganisms in the form of active elimination from the cell encoded by the chromosomes of Proteeae and Pseudomonas aeruginosa (MexXY-OprM outflow system). 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 representatives of Enterobacteriaceae. In addition, some acquired resistance was found in Klebsiella pneumoniae, Enterobacter aerogenes and Enterobacter cloacae. The reduced sensitivity of both groups to tigecycline is due to the overexpression of the gene for nonspecific active elimination of AcrAB, which provides resistance to many drugs. A reduced sensitivity to tigecycline and Acinetobacter baumannii has been described. With respect to Acinetobacter spp.,Streptococcus pneumoniae, other streptococci, Haemophilus influenzae, Moraxella catarrhrs, and Neisseria gonorrhoea and Neisseria meningitidis, have not received conclusive evidence of the efficacy of tigecycline. Therefore, the control values of the IPC are not presented. It should be noted a wide range of IPC tigecycline for Bacteroides spp. and Clostridium spp., in some cases exceeding 2 mg / l. There are only limited data on the clinical efficacy of tigecycline in enterococcal infections. Nevertheless, a positive reaction to treatment of polymicrobial intra-abdominal infections with tigecycline is shown. The prevalence of acquired resistance in certain species of bacteria may vary depending on time and geographic location. Gram-positive aerobic microorganisms are sensitive to the drug: Enterococcus avium, Enterococcus casseliflavus, Enterococcus faecocerecis, which are sensitive to the drug. vancomycin-sensitive strains), Enterococcus faecalis (including vancomycin-resistant strains), Enterococcus gallinarum, Staphylococcus aureus1,2 (including methicillin-sensitive and cut susceptible strains), Staphylococcus epidermidis (including methicillin-sensitive and resistant strains), Staphylococcus haemolyticus, Streptococcus agalactiae1, Streptococcus anginosus1,2 group (including S.anginosus, S.intermedius and S.constellatus), etc, etc, etc, etc. sensitive strains), Streptococcus pneumoniae (penicillin-resistant strains), Streptococci viridans group; gram-negative aerobes strains producing a broad spectrum β-lactamase), Legionella pneumophila3, Moraxella catarrhalis, Serratia marcescens, Bacteroides fragilis group1,2, Clostridium perfringens2, Peptostreptococcus spp.2, Peptostreptococcus micros, Prevotella spptococcus micros, Prevotella spptococcus spp.2 atypical microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae. Species that can develop acquired resistance: Acinetobacter baumannii, Burkholderia cepacia, Morganella morganii, Providencia spp., Proteus spp., Stenotrophomonas maltophilia.
Pharmacokinetics
Absorption Because tigecycline is injected IV, it is 100% bioavailable. Distribution At concentrations from 0.1 to 1 μg / ml, the binding of tigecycline to plasma proteins in vitro varies from about 71% to 89%. Pharmacokinetic studies in animals and humans have shown that tigecycline is rapidly distributed in tissues. In the human body, the equilibrium Vd tigecycline is 500-700 liters (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. The serum tigecycline Cssmax 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 × h / ml. Metabolism On average, less than 20% of tigecycline is metabolized. The main substance found in urine and feces was unchanged tigecycline, however, glucuronide, an N-acetyl metabolite and epimer of tigecycline were also detected. Tigecycline does not inhibit the metabolism mediated by the following six isoenzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19C19C19C19C19C19С19С19С19С19С19С19С19С19С19С19С19С19С19С19С19С19С19С19С19С19С19С19СР20СР, С – С… It is neither a competitive inhibitor nor an irreversible inhibitor of cytochrome P450. Administration It is noted that 59% of the prescribed dose is eliminated through the intestine (most of the unchanged tigecycline enters the bile), and 33% is excreted by the kidneys. Additional excretion pathways are glucuronization and excretion of unchanged tigecycline by the kidneys. The total clearance of tigecycline after IV infusion is 24 l / h. Renal clearance accounts for approximately 13% of the total clearance. Tigecyclin is characterized by polyexponential elimination from serum, the mean terminal T1 / 2 from serum after administering repeated doses is 42 hours, however, significant individual differences are observed. The pharmacokinetics in special clinical situations In patients with mild hepatic impairment, the pharmacokinetic profile of a single dose of tigecyclin does not change. However, in patients with moderate and severe abnormal liver function (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 <30 ml / min), the pharmacokinetic profile of a single dose of tigecycline did not change, including and on the background of hemodialysis. In patients with severe renal insufficiency, AUC is 30% more than in patients with normal renal function. The pharmacokinetics of tigecycline in elderly patients, in general, did not differ from other age groups. The pharmacokinetics of tigecycline in patients younger than 18 years of age have not been studied. Clinically significant differences clearance of tigecycline in men and women is not established. Tirecycline clearance is not dependent on race. Clearance, incl. normalized by body weight, and AUC were not significantly different in patients with different body weights, including those exceeding 125 kg. In patients with a body weight of more than 125 kg, the AUC value was 25% lower. Data on patients weighing more than 140 kg are missing.
Indications
- Complicated infections of the skin and soft tissues; - Complicated intra-abdominal infections; - Community-acquired pneumonia.
Contraindications
- Hypersensitivity to the components of the drug; - Hypersensitivity to antibiotics of the tetracycline group.
Precautionary measures
With caution should use the drug in severe liver failure.
Use during pregnancy and lactation
In pregnancy, the use of Tigacil is permissible only when absolutely necessary, when the benefit to the mother exceeds the possible risk to the fetus. There is no data on the elimination of tigecycline in human breast milk. If necessary, the appointment of tigecycline during lactation should stop breastfeeding. The experience of the use of the drug Tigacil during childbirth is not available.
Dosage and administration
The drug is administered in / in the drip for 30-60 minutes. 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 intra-abdominal infections is 5-14 days , for community-acquired pneumonia - 7-14 days. The duration of treatment is determined by the severity and localization of the infection and the patient's clinical response to treatment. Patients with mild and moderate hepatic impairment (grades A and B on the Child-Pugh scale) do not need dose adjustment. Patients with severe hepatic impairment (class C on the Child-Pugh scale) after administration of the initial dose of Tigacil 100 mg, in the subsequent preparation is prescribed 25 mg every 12 hours; Care must be taken to monitor the patient’s response to treatment. Patients with renal insufficiency and patients on hemodialysis do not need dose adjustment. Patients of advanced age do not need dose adjustment. Preparations and administration of an infusion solution. Before use, dissolve the contents of each vial. Tigacil in a 0.9% solution of sodium chloride, 5% dextrose solution for injection or Ringer's solution of lactate in an amount of 5.3 ml to get ready creates a concentration of tigecycline 10 mg / ml (5 ml of prepared solution containing 50 mg of tigecycline, each vial contains an excess of 6% of the drug).The vial is gently rotated until the drug is completely dissolved. 5 ml of the prepared solution is transferred into a vial with a 100 ml infusion solution (for a dose of 100 mg, you must take the prepared solution from 2 vials, for a 50 mg dose - from 1 vial). The maximum concentration of the final solution for intravenous infusion should not exceed 1 mg / ml. The color of the finished solution should be yellow or orange. If the solution has a different color or it defines visible inclusions, its use is not allowed. The ready solution of Tigacil can be stored at room temperature for no more than 24 hours (the ready solution can be stored in a bottle for up to 6 hours, the remaining time as a diluted final solution). Immediately after diluting the finished solution, the final solution for infusion can be stored in a refrigerator at a temperature of from 2 ° to 8 ° C for no more than 48 hours. Introduction. Tigacil should be administered in / through a separate infusion system or through a T-shaped catheter. If the IV catheter is used for the sequential administration of several drugs, it must be washed before infusing Tigacil with 0.9% sodium chloride solution, 5% dextrose solution for injection or Ringer's lactate solution. When conducting infusion should take into account the compatibility of tigecycline and other drugs administered through a single catheter.
Side effects
The most common are nausea (26%) and vomiting (18%), which usually occur at the beginning of treatment (on the first or second day of treatment) and, in most cases, have a mild or moderate course. Nausea (1%) and vomiting were the most common causes of discontinuation of Tigacil therapy. Classification of side effects: very often (≥ 1/10); often (from ≥ 1/100 to <1/10); sometimes (from ≥ 1/1000 to <1/100); rarely (from ≥ 1/10 000 to <1/1000); very rarely (≤1 / 10 000), isolated cases (spontaneous post-marketing messages). From the blood coagulation system: often - increased APTT, prothrombin time / MHO. From the hematopoietic system: sometimes - eosinophilia; in rare cases - thrombocytopenia. Allergic reactions: in rare cases - anaphylactic / anaphylactoid reactions. On the CNS side: often - dizziness. On the side of the cardiovascular system: often - phlebitis; sometimes thrombophlebitis. On 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 - severely impaired liver function 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 siteOthers: often - headache, asthenia, delayed wound healing; sometimes - chills. From laboratory parameters: often - increased blood urea nitrogen, increased serum alkaline phosphatase activity, increased serum amylase activity, hypoproteinemia; sometimes - increased creatinine in the blood, hypocalcemia, hyponatremia, hypoglycemia.
Overdose
An overdose of the drug Tigacil is not described. In / in the administration of tigecycline to healthy volunteers at a dose of 300 mg with a 60-minute duration of administration led to an increase in nausea and vomiting. Hemodialysis does not ensure the removal of tigecycline from the body.
Interaction with other drugs
With the concomitant use of Tigacil and warfarin (in a single dose of 25 mg), the clearance of R-warfarin and S-warfarin is reduced by 40% and 23%, and the AUC of warfarin is reduced by 68% and 29%, respectively. The mechanism of such interaction has not yet been established. Since tigecycline is capable of increasing both prothrombin time / INR and APTT, when using Tigacil simultaneously with anticoagulants, it is necessary to closely monitor the results of relevant coagulation samples. Warfarin does not alter Tigacil's pharmacokinetic profile. Tigecyclin is not metabolized by isoenzymes of the cytochrome P450 system. Therefore, it is expected that active substances that suppress or induce the activity of cytochrome P450 isoenzymes will not alter the clearance of Tigacil. In turn, Tigacil is unlikely to affect the metabolism of these groups of medicinal compounds. Tigacil at the recommended dose does not affect the rate and extent of absorption or digoxin clearance (500 μg followed by administration at a daily dose of 250 μg). Digoxin does not alter the pharmacokinetic profile of tigecycline. Therefore, when using Tigacil in conjunction with digoxin, dose adjustment is not required. When antibiotics are used simultaneously with oral contraceptives, the effectiveness of contraceptives may decrease. In in vitro studies, antagonism between tigecycline and other classes of frequently used antibiotics was not observed. Compatibility of Tigacyl is compatible. sodium chloride, 5% dextrose solution for injection or ringer's lactate solution.When administered via a T-shaped catheter, Tigacil, dissolved in 0.9% sodium chloride solution or 5% dextrose cream, is compatible with amikacin, dobutamine, dopamine hydrochloride, gentamicin, haloperidol, Ringer's lactate solution, lidocaine hydrochloride, metoclopram, lidocaine, metoclopramide, haloperidol, lactate, lidocaine hydrochloride, metoclopramide, lidocaine, lidocainum, metoclopramide, injectables. tazobactam (dosage form containing EDTA), potassium chloride, propofol, ranitidine hydrochloride, theophylline and tobramycin. Incompatibility When used through a T-shaped catheter Tigacil incompatible with amphotericin B, amphotericin B liposomal, diazepam, esomeprazole and omeprazole.
special instructions
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 susceptible microorganisms. Whenever possible, microbiological identification of the pathogen should be carried out and its sensitivity to tigecycline should be determined to select and correct antibiotic therapy. Tigacil can be used for empirical antibacterial monotherapy until the results of microbiological tests are obtained. Antibiotics belonging to the glycylcycline class have structural similarities to tetracycline antibiotics. Tigacil can cause adverse reactions similar to adverse reactions to tetracycline antibiotics. Such reactions can be increased photosensitivity, intracranial hypertension, pancreatitis, and anti-anabolic effect, leading to an increase in the blood urea nitrogen content, azotemia, acidosis, and hypophosphatemia. Therefore, Tigacil should be used with caution in patients with a known sensitivity to tetracycline antibiotics. Anaphylactic / anaphylactoid reactions, incl. anaphylactic shock, noted with the use of virtually 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 (isolated cases of significant liver dysfunction and liver failure are registered) and assess the ratio of the benefits and the risk of continuing treatment with Tigacil.The development of adverse reactions is possible after the therapy has been completed. Tigacil's efficacy and safety in patients with nosocomial pneumonia has not been confirmed by clinical studies. Diarrhea associated with Clostridium difficile has been noted with virtually all antibacterial drugs, including Tigacil. If you suspect diarrhea associated with Clostridium difficile or confirm this diagnosis, you may need to stop using antibiotics, other than those prescribed to treat an infection caused by Clostridium difficile. When using tigecycline, pseudomembranous colitis of various severity may develop. It is necessary to take into account the possibility of such a diagnosis in the event of diarrhea during or after completion of treatment. When prescribing Tigacil in patients with complicated intra-abdominal infections due to intestinal perforation, or in patients with sepsis or septic shock, it is necessary to consider the appropriateness of using combined antibacterial therapy. other antibiotics may contribute to the overgrowth of immune microorganisms, including the fungus . During treatment, patients should be closely monitored. Appropriate measures should be taken in the diagnosis of superinfection. The effect of cholestasis on tigecycline pharmacokinetics has not been established. Biliary excretion accounts for approximately 50% of the total excretion of tigecycline. Therefore, patients with cholestasis should be under the supervision of a physician. Experience with Tigacil for treating infections in patients with co-morbid illness is limited. The use of Tigacil during the formation of teeth can lead to discoloration of the teeth to yellow, gray, brown. Tigacil should not be used in the period of development of teeth, except in cases when other drugs are not effective or contraindicated.