Timentin

Active material: Clavulanic acid, Tikarцillin
When ATH: J01CR03
CCF: Antibiotics penicillin broad spectrum, penicillinase-resistant; активный в т.ч. в отношении синегнойной sticks
ICD-10 codes (testimony): A40, A41, H66, J01, J02, J03, J04, J15, J20, J31, J32, J35.0, J37, J42, K65.0, K81.0, K81.1, K83.0, L01, L02, L03, L08.0, M00, M86, N10, N11, N15.1, N30, N34, N41, N70, N71, N72, N73.0, T79.3, Z29.2
When CSF: 06.01.02.05.01
Manufacturer: GlaxoSmithKline Trading Company (Russia)

Pharmaceutical form, composition and packaging

Valium for solution for infusion powder from white to light yellow in colour.

Glass Bottles (10) – packs cardboard.

Valium for solution for infusion powder from white to light yellow in colour.

Glass Bottles (10) – packs cardboard.

Pharmacological action

Antibiotics penicillin broad spectrum, penicillinase-resistant. Timentin is a combined medication, composed of sodium tikarcillina – polusinteticeski karboksipenicillin with a wide spectrum of bactericidal activity and clavulanate potassium – ингибитор b-лактамаз, that are produced by many gram negative and Gram-positive bacteria. Effect of β-lactamases may lead to the destruction of some antibacterial drugs even before their effects on pathogens. Clavulanate potassium destroys this protective mechanism, blocking the action of enzymes, What makes bacteria susceptible to tikarcillinu. Clavulanate potassium has no antibacterial activity, but its combination with tikarcillinom preparation Timentin lets get the broad-spectrum antibiotic, insensitive to β-lactamazam.

Timentin has bactericidal activity in vitro against Gram negative bacteria: Acinetobacter spp., Moraxella catarrhalis, Citrobacter spp. (including Citrobacter freundii, Citrobacter different, Citrobacter amalonaticas), Enterobacter spp. (despite, that many strains of Enterobacter spp. strains in vitro, clinical efficacy of tikarcillina has been demonstrated with clavulanic acid for infections of the urinary tract), Escherichia coli, Haemophilus influenzae, Klebsiella spp. (включая Klebsiella pneumoniae), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Proteus is wonderful, Proteus vulgaris, Rettgeri Providence, Providence stuartii, Pseudomonas spp. (incl. Pseudomonas aeruginosa, Pseudomonas maltophila), Salmonella spp., Serratia spp. (including Serratia marcescens); Gram-positive bacteria: Staphylococcus aureus, Staphylococcus epidermidis (coagulase-negative strains), Staphylococcus saprophyticus, Streptococcus agalactiae * (Group), Streptococcus bovis *, Enterococcus faecalis *, Streptococcus pneumoniae *, Streptococcus pyogenes * (Group a, Beta hemolytic), Streptococcus viridans; Anaerobic bacteria: Bacteroides spp. (including Bacteroides fragilis group/Bacteroides fragilis,Bacteroides vulgatus,Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides distasonis), and non-Bacteroides fragilis (Beta-melanogennye), Clostridium spp. (including Clostridium perfiingens, Clostridium difficile, Clostridium sporogenes, Clostridium ramosum, Clostridium bifermentans *, Eubacterium spp., Fusobacterium spp. (Fusobacterium nucleatum and including Fusobacterium necrophorum *), Peptococcus spp. *, Peptostreptococcus spp. *, Veillonella spp. *.

* strains, sensitive to tikarcillinu, not producing β-laktamazu.

Pharmacokinetics

The AUC for tikarcillina is 485 µg/ml/h after the introduction 3.1 and g 3.2 g. The corresponding values for clavulanic acid make up 8.2 µg/ml/h and 15.6 µg/ml/h. After the on/in infusion in doses of tikarcillina 3.1 and g 3.2 g for 30 m, C_max in the blood plasma is achieved immediately after the infusions and constitute 330 ug/mL for both doses. In doing so, pharmacokinetic parameters clavulanic acid make up 8 ug / ml (to 3.1 g tikarcillina) and 16 ug / ml (to 3.2 g tikarcillina).

Serum concentrations in adults after a 30-minute infusion tikarcillina dose 3.2 g

Distribution

Tikarcillin distributed in the tissues and organs of injecting a. It shows the penetration of tikarcillina in bile, pleural fluid, cerebrospinal fluid. T_1/2 from the blood plasma is inversely proportional to the creatinine klirensu. Plasma protein binding is 50% for tikarcillina and 25% for clavulanic acid.

Deduction

Average T_1/2 from serum, defined in healthy volunteers, for tikarcillina and clavulanic acid is 68 Mines and 64 min, respectively. About 60-70% tikarcillina and 35-45% clavulanic acid is excreted unchanged to the kidneys in the first hours after the administration of a single dose of the drug (in healthy volunteers with normal renal function). Through 2 h after the/in infusions 3.2 grams of the drug concentration in urine exceeds tikarcillina 1500 ug / ml, and the concentration of clavulanic acid exceeds 70 ug / ml. Through 4-6 hours after administration at a dose 3.2 g concentration in urine is 2 ug / ml.

Pharmacokinetics in special clinical situations

Tikarcillin can be displayed by using dialysis, excretion rate depends on the type of dialysis.

Testimony

Timentin is indicated for the treatment of infections, caused by pathogens with established or suspected sensitivity, such as:

-infections of the bone and connective tissue, caused by-producing β-laktamazu strains of Staphylococcus aureus;

- Infections in gynecology, incl. endometritis, вызванные продуцирующими β-лактамазу штаммами Bacteroides melaninogenicus*, Enterobacter spp. (включая Enterobacter cloacae*), Escherichia coli, Klebsiella pneumoniae*, Staphylococcus aureus, Staphylococcus epidermidis;

- Intra-abdominal infections, incl. peritonitis, вызванные продуцирующими β-лактамазу штаммами Escherichia coli, Klebsiella pneumoniae и Bacteroides fragilis*;

- Infections of the lower respiratory tract, caused by-producing β-laktamazu strains of Staphylococcus aureus, Haemophilus influenzae* и Klebsiella spp.*;

- Septicemia, включая бактериемию, caused by-producing β-laktamazu strains of Klebsiella spp. *, Escherichia coli*, Staphylococcus aureus *, Pseudomonas aeruginosa * (and other Pseudomonas spr. *);

- Infections of the skin and subcutaneous tissue, caused by-producing β-laktamazu strains of Staphylococcus aureus, Klebsiella spr and Escherichia coli *;

- Urinary tract infections (uncomplicated and complicated), вызванные продуцирующими β-лактамазу штаммами Escherichia coli, Klebsiella spr., Pseudomonas aeruginosa * (and other Pseudomonas spr. *), Citrobacter spr. *, Enterobacter cloacae*, Serratia marcescens * and * Staphylococcus aureus.

* effective against microorganisms was shown less than for 10 infections in each Nosological group.

Dosage regimen

Timentin can be entered as in/in drip infusions or/Jet injections. The product is not intended for a/m injection. Spacing shall not be less than infuzyami more 4 no. Treatment should be continued for 48-72 hours after the disappearance of clinical symptoms.

To adults and children weighing more than 40 kg the average dose is Timentina 3 g every 6 or 5 g every 8 no. The maximum dose – 3 g every 4 no.

To children weighing less than 40 kg the average dose is Timentina 75 mg / kg every 8 no. The maximum dose – 75 mg / kg every 6 no.

To preterm infants weighing less than 2 kg – 75 mg / kg every 12 no, to preterm infants weighing more than 2 kg – 75 mg / kg every 8 no.

Elderly patients dose adjustment is not required.

At human kidney function in adults and children weighing more than 40 kg the drug is prescribed in the following doses.

At human kidney children weighing less than 40 kg the drug is prescribed in the following doses.

There is no precise data for the dosage recommendations have preterm infants with impaired renal.

There is no precise data for the dosage recommendations when hepatic dysfunction.

Terms of preparation and administration solutions

For preparation of a solution for in/in drip infusions as a solvent recommended water for injection or dextrose solution (Glucose) for on/in infusions for no more 5%. Sterile powder vials 1.6 or g 3.2 g before breeding in bulk for infusion is dissolved approximately 10 mL of solvent. After that it is recommended to apply the following amounts of solvents.

Timentina each dose introducing/in drip for 30-40 m. The introduction is not recommended for longer periods of time, tk. This can lead to subterapevticheskim concentrations of the drug, under which reduced its effectiveness.

For preparation of a solution for in/in a Jet injections sterile powder dissolved in 10 ml (bottle 1.6 g) or 20 ml (bottle 3.2 g) water for injection. Solution enter slow struino within 3-4 m. Timentin can be entered directly into a vein or via IV.

By dissolving Timentina heat. Cooked solution usually has light straw color.

Unexpended after the introduction of the solution in any number of further use shall not be.

Infusion solution immediately before use is recommended, However, the following infusion solutions Timentina stable at 25° c for the following periods of time:

Side effect

From the digestive system: nausea, vomiting, diarrhea; In very rare cases – psevdomembranoznыy colitis.

From the Hepatobiliary system: a moderate increase in AST and/or ALT in patients, treated with antibiotics ampicillinovogo series; rarely – hepatitis and cholestatic jaundice. These phenomena also observed other antibiotics penicillin and cephalosporin.

CNS: rarely – convulsions (in patients with impaired renal function and in the appointment of high doses of the drug).

From the hematopoietic system: rarely – thrombocytopenia, leukopenia, eozinofilija, decrease in hemoglobin.

From the blood coagulation system: rarely – lengthening protrombinovogo time and bleeding time. May increase bleeding.

Allergic reactions: skin rash, itch, hives, anaphylactic reactions; rarely – bullous reaction (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).

When you see any application Timentina gipercuvstvenosti reactions should stop.

Local reactions: pain, burning sensation, redness and induration at the injection site and throm with on/in the introduction.

Other: rarely – kaliopenia.

Contraindications

-premature babies with impaired renal;

- Hypersensitivity to beta-lactam antibiotics (incl. penitsillinam and zefalosporynam).

Very rarely reported on the development of hypokalemia on the background of the use of the drug. Therefore, you must use caution in appointing patients with electrolyte imbalances or fluid. It is recommended that periodic monitoring of the concentration of potassium in the blood serum of patients, long-term receiving medication.

Some patients in the treatment of Timentinom observed a modest increase ALT and AST. In this regard, patients with severe liver dysfunction should be appointed with Timeitin caution.

Pregnancy and lactation

IN animal studies There were no teratogenic action of the preparation. There are limited data on its use in pregnancy. The decision to appoint drug in pregnancy should be taken with extreme caution. In this regard, in appointing pregnant women Timentina doctor should carefully weigh the potential benefits and potential risks, associated with the use of this drug.

You can assign Timentin lactation period, but, taking into account the, that a trace amount of the drug pass into breast milk, account should be taken of the risk of sensitization in the newborn.

Cautions

Because, that serious, in some cases, lethal, hypersensitivity reactions (incl. and anaphylactic reactions) observed in patients, previously treated with beta-lactam antibiotics, You must Timentina before assignment to ascertain the absence of a history of similar reactions. In case of allergic reactions, discontinue use of the drug and conduct a supportive therapy, development of anaphylactic reactions require immediate action in accordance with the schemes.

Despite, that Timentin has low toxicity, peculiar antibiotics penicillin, When conducting long-term therapy, it is recommended to periodically evaluate kidney function, liver and hematopoiesis.

Increased bleeding was observed in patients, treated with beta-lactam antibiotics. Similar reaction, perhaps, associated with violation of the collapse, platelet aggregation and lengthening protrombinovogo time (mainly in patients with renal insufficiency). When developing bleeding should stop the drug and undertake appropriate therapeutic interventions.

In the appointment Timentina patients, We are on a salt-free diet, sodium content must be taken into account in the composition of.

Prolonged use of the drug can lead to the growth of non-sensitive strains of.

In the treatment of mixed infections, caused by strains, sensitive to tikarcillinu (incl. -producing β-laktamazu), does not require the additional appointment of other antibiotics.

To ensure adequate therapy, it was necessary to conduct the appropriate tests for susceptible to antibiotic. But, given the wide range of bactericidal activity against grampolaugitionah and gramotricationah strains, combination of tikarcillina and clavulanic acid is used as first-line therapy for the treatment of mixed infections until, until the pathogen is defined. Was shown the effectiveness of the combination tikarcillina and clavulanic acid, appointed as monotherapy in some severe infections, for treatment which usually apply combinations of antibiotics. In vitro test results showed synergistic effect aminoglikozidov and tikarcillina combinations with clavulanic acid against certain strains of Pseudomonas aeruginosa, that suggests the effectiveness of such combination therapy (especially in patients with immunocompromised). In this case, both drugs should be prescribed in the recommended therapeutic doses. After receiving test results on sensitivity, therapy, if necessary, It should be adjusted.

Overdose

Symptoms: nausea, vomiting, diarrhea. It is also possible the development imbalance fluid volume and electrolytes. Overdose some patients may develop increased neuromuscular excitability and convulsive seizures.

Treatment: with the development of the clinical picture of drug overdose shown symptomatic therapy. In the case of an overdose tikarcillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

Drug Interactions

Not recommended socetannoe application with probenicidom. Probenecid reduces the secretion of kanalcievuju tikarcillina. Simultaneous application of Probenecid retards breeding tikarcillina, but does not affect excretion of clavulanic acid.

Timentin exhibits synergy with aminoglikozidami against certain microorganisms, incl. Pseudomonas aeruginosa. In this connection, we recommend that you assign Timentin in combination with aminoglikozidami to treat life-threatening infections, especially patients with impaired immunity. In this case, the drugs injected separately in the recommended doses.

Clavulanic acid, may cause non-specific binding of IgG and albumin with erythrocyte membranes, that leads to lozhnopolozhitelnym results sample Kumbsa.

Like other antibiotics, tikarcillin can change the composition of intestinal microflora, that leads to low estrogen reabsorption and, Consequently, effectiveness of combined oral contraceptives.

Pharmaceutical interaction

When a combination of application Timentina with aminoglycoside antibiotics should not be mixed in the same syringe, containers or systems for on/in infusions, tk. This can lead to decreased activity of aminoglycosides.

Timentin insufficiently stable in infusion fluids, containing bicarbonate.

It is not recommended to mix Timentin with preparations of blood and other fluids proteinopodobnymi, such as protein hydrolysates, as well as with lipid emulsions.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at a temperature of 2 ° to 8 ° C. Shelf life – 3 year.