Timentin - instructions for use, dose, side effects, contraindications

Active substanceTicarcillin + Clavulanic acidTicarcillin + Clavulanic acid

Similar drugsTo uncover

lyophilizate d / infusion

GlaxoSmithKline group of companies Unknown

Dosage form: & nbsplyophilizate for solution for infusion

Composition:

Active substances: ticarcillin disodium equivalent to ticarcillin 1.5 g or 3 g; potassium clavulanate equivalent to clavulanic acid 100 mg or 200 mg.

Description:

Powder from white to light yellow color.

Pharmacotherapeutic group:Antibiotic-penicillin semisynthetic + beta-lactamase inhibitor

ATX: & nbsp

J.01.C.R. Combinations of penicillins (including those with beta-lactamase inhibitors)

Pharmacodynamics:

Pharmacodynamics

Tymetin is a combined preparation of ticarcillin sodium, a semi-synthetic carboxypenicillin with a broad spectrum of bactericidal activity, and clavulanate of a potassium inhibitor (3-lactamase p-lactamase produced by many gram-negative and gram-positive bacteria.) The action of p-lactamases may lead to the destruction of some antibacterial drugs before they begin Effects on pathogens Potassium clavulanate destroys this protective mechanism by blocking the action of enzymes, which makes bacteria sensitive to ticar cillin.Potassium clavulanate does not have antibacterial activity, but its combination with ticarcillin in the preparation of Tymantin allows to obtain a broad-spectrum antibiotic that is insensitive to P-lactamases.

Tymmentin has a bactericidal effect in vitro for a wide range of microorganisms.

Gram-negative bacteria:

Acinetobacter species " Moraxella catarrhalis
Citrobacter species, including C. freundii, C. diversus and C. amalonaticus
Enterobacter species (despite the fact that many strains Enterobacter species resistant in vitro., the clinical efficacy of Ticarcillinia with clavulanic acid in urinary tract infections was demonstrated)
Escherichia coli
Haemophilus influenzae
Klebsiella species, including TO. pneumoniae
Morganella morganii
Neisseria gonorrhoeae
Neisseria meningitidis#
Proteus mirabilis
Proteus vulgaris
Providencia rettgeri
Providencia stuartii

Pseudomonas aeruginosa

Pseudomonas including P, maltophilia
Salmonella species

Serratia species, including S. marcescens

Gram-positive bacteria:

Staphylococcus aureus

Staphylococcus epidermidis (coagulase-negative)
Staphylococcus saprophyticus
Streptococcus agalactiae # (group B)
Streptococcus bovis #
Enterococcus faecalis #
Streptococcus pneumoniae # (Dipplococcus pneumoniae)
Streptococcus pyogenes # (group A, beta-hemolytic)
Viridans Group streptococci

Anaerobic bacteria:

Bacteroides species, including AT. fi^Aagilis group (AT. fragilis, AT. vulgatus, AT. thetaiotaomicron, AT. ovatus, AT. distasonis), and non-i? fragilis (beta-melanogenic)
Clostridium species including C. perfringens, C. difficile, C. sporogenes, C. ramosum and C. bifermentans #
Eubacterium species
Fusobacterium species including F. nucleatum and F. necrophorum #
Peptococcus species #

Peptostreptococcus species #

Veillonella species

The Sign # Ticarcillin-sensitive strains not producing beta-lactamase were noted.

Pharmacokinetics:

The average area under the concentration-time curve for ticarcillin is 485 μg / ml / h after administration of 3.1 g and 3.2 g. The corresponding values for clavulanic acid are 8.2 μg / ml / h and 15.6 μg / ml / h. After intravenous infusion tikarsinshina in doses of 3.1 g and 3.2 g for 30 minutes, the maximum plasma concentrations are reached immediately after the infusion is complete and are 330 μg / ml for both doses. The pharmacokinetic parameters of clavulanic acid are 8 μg / ml (for 3.1 g of ticarcillin) and 16 μg / ml (for 3.2 g of ticarcinine).

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

0	15 minutes	30 min	1 h	1.5 h	3.5 hrs	5,5 h
Ticarcillin (μg / ml)
336	214	186	122	78	29	10
301 -386	180 -258	160 -218	108 -136	33 -113	19-44	5-15
'Clavulanic acid (μg / ml)
15.8	8.3	5.2	3.4	2.5	0.5	0
11.7-21.0	6.4 -10.0	3.5 - 6.3	1.9-4.0	1.3 -3.4	0.2 - 0.8

Distribution

Ticarcillin is distributed in organs and tissues with parenteral administration. The penetration of ticarcillin into bile, pleural fluid, cerebrospinal fluid. The period of excretion from the blood plasma is inversely proportional to the creatinine clearance. Binding to plasma proteins is 50% for ticarcillin and 25% for clavulanic acid.

Excretion

The mean half-life of serum from healthy volunteers for ticarcillin and clavulanic acid is 68 minutes and 64 minutes, respectively.Approximately 60-70% of ticarcillin and 35-45% of clavulanic acid are excreted unchanged by the kidneys during the first hours after the administration of a single dose of the drug (in healthy volunteers with normal renal function). Two hours after intravenous infusion, 3.2 g of the drug concentration of ticarcillin in the urine is more than 1500 μg / ml, and the concentration of clavulanic acid exceeds 70 μg / ml. In 4-6 hours after the administration of the drug at a dose of 3.2 g, the concentration in urine is 2 μg / ml.

Patients with impaired renal function

Ticarcillin can be excreted by dialysis, and the rate of elimination depends on the type of dialysis.

Indications:

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

* Bone and connective tissue infections caused by beta-lactamase-producing strains Staphylococcus aureus

Infections in gynecology, including endometritis, caused by beta-lactamase-producing strains Bacteroides melaninogenicus#, kinds Enterohacter (including E. cloacae #), Escherichia coli, Klebsiella pneumoniae #, Staphylococcus aureus and Staphylococcus epidermidis Intra-abdominal infections, including peritonitis, caused by beta-lactamase-producing strains of Escherichia coli, Klebsiella pneumoniae and Bacteroides fragilis #
Lower respiratory tract infections caused by beta-lactamase-producing strains of Staphylococcus aureus, Haemophilus influenzae # and Klebsiella species #
Septicemia, including bacteremia, caused by beta-lactamase producing strains of Klebsiella species #, E. coli #, Staphylococcus aureus #, Pseudomonas aeruginosa # (and other Pseudomonas species #)
Infections of the skin and subcutaneous tissue caused by beta-lactamase-producing strains of Staphylococcus aureus, Klebsiella species # and E. coli #
Urinary tract infections (uncomplicated and complicated) caused by beta-lactamase-producing strains of E. coli, Klebsiella species, Pseudomonas aeruginosa # (and other Pseudomonas species #), Citrobacter species #, Enterobacter cloacae #, Serratia marcescens # and Staphylococcus aureus #
Effective against microorganisms marked with #, was
is indicated for less than 10 infections in each nosological group.

Contraindications:

Hypersensitivity to beta-lactam antibiotics (including penicillins and cephalosporins). The drug is contraindicated in premature infants with impaired renal function.

Carefully:

Very rarely reported on the development and hypokalemia in the background of the drug. Therefore, care must be taken when prescribing to patients with an electrolyte or fluid imbalance. It is recommended that the potassium concentration in the blood serum be monitored periodically in patients who receive the drug for a long time.In some patients with treatment with Timentin, there was a moderate increase in alanine and aspartic aminotransferases. In this regard, a patient with severe impairment of liver function, Timentine should be administered with caution.

Pregnancy and lactation:

Pregnancy

In studies on animals, the teratogenic effect of the drug was not detected. There are limited data on its use during pregnancy. The decision to prescribe the drug during pregnancy should be taken with extreme caution. In this regard, when appointing Timentin pregnant women, a doctor should carefully weigh the potential benefits and potential risks associated with the use of this drug.

Breastfeeding period

Timentin can be given during breastfeeding, but given that trace amounts of the drug enter breast milk, the risk of developing a sensitization in a newborn should be considered.

Dosing and Administration:

Timentin is administered intravenously: struino slowly (for 3-4 minutes) or drip (for 20-30 minutes).

Intervals between infusions should be at least 4 hours.

Treatment should continue for 48-72 hours after the disappearance of clinical symptoms.

Adults and children weighing more than 40 kg:

normal dosing regimen per day
the maximum dose per day

Children with a body weight of less than 40 kg:

normal dosing regimen per day
maximum dose and frequency of administration

Premature neonates:

body weight less than 2 kg
body weight more than 2 kg

Elderly patients

No dosage adjustment is required.

3 g every 6 hours or 5 g every 8 hours 3 g every 4 hours

75 mg / kg every 8 hours 75 mg / kg every 6 hours

75 mg / kg every 12 hours 75 mg / kg every 8 hours

The drug is not intended for intramuscular injection!

Dosage regimen for renal dysfunction

	Adults and children weighing more than 40 kg:
1.	Creatinine clearance more than 60 ml / min	3 g every 4 hours
2.	Creatinine clearance 30-60 ml / min	2 g every 4 hours or 3 g every 8 hours
3.	Creatinine clearance 10-30 ml / min	2 g every 8 hours or 3 g every 12 hours
4.	Creatinine clearance less than 10 ml / min	1 g every 6 hours or 2 g every 12 hours or 3 g every 24 hours
5.	Creatinine clearance less than 10 ml / min (with	1 g every 12 hours or 2 grams
	concomitant liver dysfunction)	every 24 hours
b.	Patients on peritoneal dialysis	1 g every 6 hours or 2 g every 12 hours or 3 g every 24 hours

7.Patients on hemodialysis 1 g every 6 hours or 2 g every 12 hours or 3 g every 24 hours, adding 3 g each time after dialysis

Children with a body weight of less than 40 kg:

Creatinine clearance more than 30 ml / min 75 mg / kg every 8 hours
Creatinine clearance 10-30 ml / min 5 mg / kg every 8 hours
Creatinine clearance less than 10 ml / min 5mg / kg every 12 hours
Premature neonates There is no precise data for recommending a dosing regimen

Dysfunction of the liver

There is no precise data for recommending a dosing regimen

Preparation of the solution

Intravenous drip infusion.

To prepare the solution as a solvent, it is recommended to use water for injection or glucose solution, intended for intravenous administration (not more than 5%),

Before dilution in infusion tanks, sterile powder (from vials containing 1.6 g and 3.2 g of the preparation) is dissolved in approximately 10 ml of the solvent. After that, the following volumes of solvents are recommended:

Bottle	Water for injections	Glucose solution for
		intravenous administration
		(not more than 5%)
1.6 g	50 ml	100 ml
3.2 g	100 ml	100-150 ml

Each dose of Timentine is administered intravenously calve for 30-40 minutes. It is not recommended to administer the drug for a longer period of time.this can lead to sub-therapeutic concentrations, in which its effectiveness decreases.

Intravenous Injection Injection.

The sterile powder is dissolved in 10 ml (a vial containing 1.6 g of the preparation) or in 20 ml (a bottle containing 3.2 g of the preparation) of water for injection.

The solution is injected slowly for 3-4 minutes. Timentin can be injected directly into a vein or through a dropper.

When dissolving Timentin, heat is released. The prepared solution usually has a light straw color.

Unspent solution is not subject to further use! Stability of solutions and their storage

It is recommended to prepare the solution immediately before use.

Although the Timentin solution should be used immediately after preparation, there are data on the stability of solutions prepared using various solvents at 25 ° C for the following periods:

Solvent	Period stability at 25 ° C
Water for injections	24	hours
Glucose solution for intravenous infusions (5% m / v)	12	hours
Solutions for intravenous infusions of sodium chloride (0.18%	24	hours
m / v) and glucose (4% m / v)
A solution of sodium chloride for intravenous infusions (0.9%	24	hours
m / v)
Dextran 40 for intravenous infusions (10% m / v) in	6 hours
glucose solution for intravenous infusions (5%)
Dextran 40 for intravenous infusions (10% m / v) in	24	hours
sodium chloride solution for intravenous infusions (0.9%)
Glucose solution for intravenous infusions (10% m / v)	6 hours
Solution of sorbitol for intravenous infusions (30% m / v) Solution of sodium lactate for intravenous infusions (M / 6) Combined sodium lactate solution for intravenous infusions (Ringer's lactate solution, Hartmann's solution)	6 hours 12 hours 12 hours

Side effects:

Hypersensitivity reactions

Skin rashes, itching, hives,

anaphylactic reactions.

Very rarely - bullous reactions (including: erythema multiforme, Stevens-Johnson syndrome, toxic

epidermal necrolysis).

When any hypersensitivity reactions occur, the use of

Tiententine should be discontinued.

From the gastrointestinal tract Nausea, vomiting and diarrhea. In very rare cases - pseudomembranous colitis.

From the hepatobiliary system Moderate increase in serum concentrations of aspartic

aminotransferase and / or alanine aminotransferase in patients who received ampicillin antibiotics. Highly rarely - hepatitis and cholestatic jaundice. These phenomena were also observed with the use of other antibiotics of penicillin and cephalosporin series.

From the excretory system

Rarely, hypokalemia. Rarely -

hemorrhagic cystitis.

From the central nervous system Rarely - convulsions, in particular, in patients with impaired renal function and with the appointment of high doses of the drug.

On the part of the blood system

Rarely, thrombocytopenia, leukopenia,

eosinophilia, a decrease in the level of hemoglobin,

prolongation of prothrombin time and

bleeding time. Possible amplification

bleeding.

Local Reactions

Pain, burning sensation, redness and tightness at the injection site and thrombophlebitis with intravenous application.

Overdose:

Symptoms

When an overdose of the drug in the patient may appear such symptoms as: nausea, vomiting, diarrhea. It is also possible to develop an imbalance in the volume of fluid and electrolytes. In overdose, in some patients, increased neuromuscular excitability and convulsive seizures may develop.

Treatment

With the development of a clinical picture of drug overdose, symptomatic therapy is indicated. In case of an overdose, ticarcildin and clavulanic acid can be removed from the bloodstream by hemodialysis.

Interaction:

It is not recommended combined use with probenicid. Probenecid reduces the tubular secretion of ticarcillin. Simultaneous application with probenecid leads to a slower release of ticarcillin, but does not affect the excretion of clavulanic acid.

Tymantin shows synergism with aminoglycosides against a number of microorganisms, including Pseudomonas. In this regard, it is recommended to appoint Timentin in combination with aminoglycosides for the treatment of life-threatening infections, especially for patients with impaired immunity. In this case, these drugs are administered separately in the recommended doses.

Clavulanic acid, can cause nonspecific binding IgG and albumin with erythrocyte membranes, which leads to false positive results of the Coombs test.

Like - and other antibiotics, ticarcillin can change the composition of the intestinal microflora, which leads to a low reabsorption of estrogen and, as a consequence,the effectiveness of combined oral contraceptives.

Pharmaceutical incompatibility

When combined with titmentin with aminoglycosides, antibiotics should not be mixed in a single syringe, containers or systems for intravenous infusions, because this can lead to a decrease in the activity of aminoglycosides.

Clavulanic acid, can cause nonspecific binding IgG and albumin with erythrocyte membranes, which leads to false positive results of the Coombs test.

Like - and other antibiotics, ticarcillin can change the composition of the intestinal microflora, which leads to a low reabsorption of estrogen and, as a result, a decrease in the effectiveness of combined oral contraceptives.

Pharmaceutical incompatibility

Special instructions:

In connection with the fact that serious, in some cases lethal, hypersensitivity reactions (including anaphylactic reactions) were noted in patients who had previously received beta-lactam antibiotics, it is necessary before the appointment of Timentin to establish accurately the absence of such reactions in the anamnesis. In case of allergic reactions, the drug should be discontinued and maintenance therapy should be carried out, the development of anaphylactic reactions requires urgent measures in accordance with the adopted regimens.

Despite the fact that Timentin has a low toxicity peculiar to penicillin antibiotics, it is recommended to periodically evaluate the kidneys, liver and hematopoiesis during long-term therapy.

Increased bleeding was noted in patients who received beta-lactam antibiotics. Similar reactions may be associated with a disorder of clotting, platelet aggregation, and prolongation of prothrombin time (mainly in patients with renal insufficiency). With the development of bleeding, the drug should be withdrawn and appropriate therapeutic measures taken.

When appointing Tymettin, patients on a salt-free diet should take into account the sodium content of the drug.

Long-term use of the drug may lead to an increase in insensitive strains of the pathogen.

In patients with impaired renal function, the dose of Thymenthin is corrected in accordance with the recommendations in section "Dosage regimen in case of impaired renal function". In the treatment of mixed infections caused by strains sensitive to ticarcillin (including those producing beta-lactamase), no additional prescription of other antibiotics is required.

In order to ensure adequate therapy, it is necessary to conduct appropriate tests for the sensitivity of the pathogen to the antibiotic.But, given the wide range of bactericidal activity against Gram-positive and Gram-negative strains, the combination of ticarcillin and clavulanic acid is used as first-line therapy for the treatment of mixed infections until the causative agent is identified. The efficacy of a combination of ticarcillin and clavulanic acid has been shown to be used as a monotherapy for certain severe infections, for which combinations of antibiotics are commonly used. Test results in vitro showed a synergistic effect of aminoglycosides and combinations of ticarcillin with clavulanic acid in relation tothe specific strains Pseudomonas aeruginosa, which suggests the effectiveness of such a combination therapy (especially in patients with weakened immunity). In this case, both drugs should be administered at the recommended therapeutic doses. After receiving the results of the sensitivity tests, therapy, if necessary, should be adjusted.

Form release / dosage:

Lyophilizate for the preparation of a solution of 1.5 g +100 mg or 3.0 g + 200 mg.

Packaging:

Lyophilizate for the preparation of a solution of 1.5 g +100 mg or 3.0 g + 200 mg per bottle of clear glass, sealed with a rubber stopper, crimped with an aluminum cap.

For 10 vials along with the instructions for use are placed in a cardboard box.

Storage conditions:

Store at + 2-8 ° C Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012635 / 01

Date of registration:07.08.2007

Date of cancellation:2017-05-25

The owner of the registration certificate:GlaxoSmithKline group of companies GlaxoSmithKline group of companies Unknown

Manufacturer: & nbsp

SmithKline Beecham Pharmaceuticals United Kingdom

Representation: & nbspGlaxoSmithKline group of companies GlaxoSmithKline group of companies Unknown

Information update date: & nbsp25.05.2017

Illustrated instructions

Instructions

Timentin (Timentin)