Tacillin J - instructions for use, dose, side effects, contraindications

Composition:Composition:
1 bottle contains:
Active substances:
piperacillin sodium 2084.9 mg, equivalent to piperacillin 2000 mg and sodium tazobactam 268.3 mg, equivalent to tazobactam 250 mg
or
piperacillin sodium 4169.9 mg, equivalent to piperacillin 4000 mg and sodium tazobactam 536.6 mg, equivalent to tazobactam 500 mg.

Description:White or almost white powder.

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

ATX: & nbsp

J.01.C.R.05 Piperacillin in combination with enzyme inhibitors

Pharmacodynamics:Piperacillin is a semi-synthetic bactericidal broad-spectrum antibiotic,It is active in many gram-positive and gram-negative aerobic and anaerobic bacteria. Piperacillin inhibits the synthesis of the membrane of the cell wall of the microorganism. Tazobactam is a sulfonic derivative of triazolmethylpenicillic acid, a potent inhibitor of many beta-lactamases (including plasmid and chromosomal beta-lactamases), which often cause resistance to penicillins and cephalosporins, including third-generation cephalosporins. The presence of tazobactam in the combination drug enhances antimicrobial activity and expands the spectrum of piperacillin action by including bacteria that form beta-lactamases, which are usually resistant to piperacillin and other beta-lactam antibiotics.
The drug is active against:
Gram-negative bacteria: producing and non-producing beta-lactamase strains Escherichia coli, Citrobacter spp. (including Citrobacter freundii, Citrobacter divers us), Klebsiella spp. (including Klebsiella oxyioca, Klebsiella pneumoniae), Enterobacter spp. (including Enterobacter cloaca, Enterobacter aerogenes), Proteus vulgaris, Proteus mirabilis, Providencia rettgery, Providencia stuartii, Plesiomonas shigelloides, Morganella morganii, Serratia spp. (including Serratia marcescens, Serratia liquifaciens), Salmonella spp., Shigella spp., Pseudomonas aeruginosa and other Pseudomonas spp. (including Pseudomonas cepacia, Pseudomonas fluorescens), Xanthamonas maltophilia, Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella spp.(including Branhamella catarrhalis), Acinetobacter spp., Haemophilus influenzae, Haemophilus parainfluenzae, Pasteurella multocida, Yersinia spp., Campylobacter spp., Gardnerella vaginalis.
Gram-positive bacteria: producing and non-producing beta-lactamase strains Streptococcus spp. (including Streptococcus pneumoniae, Streptococcus pyogenes. Streptococcus bovis, Streptococcus, agalactiae. Streptococcus spp. group viridans of subgroup C and G), Enterococcus spp. (Enterococcus faecalis, Enterococcus faecium), Staphylococcus aureus (sensitive to methicillin), Staphylococcus saprophyticus, Staphylococcus epidermidis (coagulase negative), Listeria monocytogenes, Nocardia spp.
Anaerobic bacteria: producing and not producing beta-lactamase strains Bacteroides spp. (Bacteroides bivius, Bacteroides disiens, Bacteroides capillosus, Bacteroides melaninogenicus, Bacteroides oralis), subgroups of Bacteroides fragilis (Bacteroides fragilis, Bacteroides vulgatus, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniform is, Bacteroides asaccharolyticus), Peptostreptococcus spp., Fusobacterium spp ., Eubacterium spp., Clostridium spp. (including Clostridium difficile, Clostridium perfringens), Veilonella spp. and Actynomyces spp.

Pharmacokinetics:The mean concentrations of piperacillin and tazobactam in plasma in equilibrium are presented in Tables 1-2. The maximum concentrations of piperacillin and tazobactam in plasma are reached immediately after completion of intravenous administration.
Table 1

Equilibrium plasma concentrations in adults after a five-minute intravenous injection of piperacillin / tazobactam

Concentrations of piperacillin in plasma (μg / ml)

The dose of piperacillin / tazobactam	5** mines	30 mines	1 h	2h	3 hours	4 h
2g / 250mg	237	76	38	13	6	3
4g / 500mg	364	165	92	37	16	7

Concentrations of tazobactam in plasma (μg / ml)

The dose of piperacillin / tazobactam	5** mines	30 mines	1 h	2 h	3 hours	4 h
2g / 250mg	23.4	8.0	4.5	1.7	0.9	0.7
4g / 500mg	34.3	17.9	10.8	4.8	2.0	0.9

Ending 5 minute introduction

Table 2

Equilibrium plasma concentrations in adults after a thirty-minute intravenous injection of piperacillin / tazobactam

Concentrations of piperacillin in plasma (μg / ml)

The dose of piperacillin / tazobactam	30** mines	1 h	1.5 h	2 h	3 hours	4 h
2g / 250mg	134	57	29	17	5	2
4g / 500mg	298	141	87	47	16	7

Concentrations of tazobactam in plasma (μg / ml)

The dose of piperacillin / tazobactam	30** mines	1 h	1.5 h	2h	3 hours	4h
2g / 250mg	14.8	7.2	4.2	2.6	1.1	0.7
4g / 500mg	33.8	17.3	11.7	6.8	2.8	1.3

Ending 30 minute introduction

When the dose of the combination is increased piperacillin 2 g / tazobactam 250 mg to 4 g / 500 mg, respectively, a disproportionate increase (approximately 28%) of the concentration of piperacillin and tazobactam.
The binding to plasma proteins of both piperacillin and tazobactam is approximately 30%, while the presence of tazobactam does not affect this parameter of piperacillin, and the presence of piperacillin is tazobactam.
Piperacillin / tazobactam is widely distributed in tissues and body fluids, including in the intestinal mucosa, gall bladder, lungs, bile, female genitalia (uterus, ovaries and fallopian tubes) and bones. The average concentrations in tissues are from 50 to 100% of the concentration in the plasma.
Piperacillin is metabolized to a low-activity deshetylmetabolite; tazobactam - before the inactive metabolite. Piperacillin and tazobactam are excreted by the kidneys through glomerular filtration and tubular secretion. Piperacillin is rapidly excreted unchanged, 68% of the dose is detected in the urine. Tazobactam and its metabolite are rapidly excreted by renal excretion, 80% of the dose taken is unchanged, and the remaining amount is in the form of a metabolite. Piperacillin, tazobactam and desethylpiperacillin are also excreted with bile and excreted by the intestine.
The half-life of piperacillin and tazobactam from plasma is 0.7-1.2 hours. With a decrease in creatinine clearance, the half-life of piperacillin and tazobactam is prolonged.
Impaired renal function
As the creatinine clearance decreases, the half-lives of piperacillin and tazobactam increase. With a decrease in creatinine clearance below 20 ml / min, the half-lives of piperacillin and tazobactam, compared with patients with normal renal function, increase 2 and 4 times, respectively.
During hemodialysis, 30 to 50% of piperacillin and 5% of the dose of tazobactam in the form of a metabolite are excreted.When carrying out peritoneal dialysis, respectively, about 6 and 21% of piperacillin and tazobactam are excreted, with 18% of the tazobactam being excreted in the form of its metabolite.
Impaired liver function
Although in patients with impaired liver function, the half-lives of piperacillin and tazobactam increase, dose adjustment is not required.

Indications:Infectious-inflammatory diseases caused by microorganisms sensitive to piperacillin / tazobactam.
Adults and children over 12 years of age:
- Lower respiratory tract infections;
- Urinary tract infections (complicated and uncomplicated);
- Intraabdominal infections;
- Infections of the skin and soft tissues;
- Septicemia;
- Gynecological infections (including endometritis and adnexitis in the postpartum period);
- Bacterial infections in patients with neutropenia (in combination with aminoglycosides);
- Infections of bones and joints;
- Mixed infections (caused by gram-positive / gram-negative aerobic and anaerobic microorganisms).
Children between the ages of 2 and 12:
- Intraabdominal infections;
- Infections against neutropenia (in combination with aminoglycosides).

Contraindications:Hypersensitivity to beta-lactam antibiotics (including penicillins, cephalosporins), other components of the drug or to beta-lactamase inhibitors. Children under 2 years.

Carefully:Severe bleeding (including history), cystic fibrosis (increased risk of hyperthermia and skin rash), pseudomembranous colitis, childhood, kidney failure (creatinine clearance less than 20 ml / min), patients on hemodialysis, with joint application of high doses of anticoagulants, with hypokalemia.

Pregnancy and lactation:There is insufficient data on the use of a combination of piperacillin / tazobactam or both drugs separately in pregnant women. Piperacillin and tazobactam penetrate the placental barrier. Pregnant women drug can be prescribed only in those cases when the expected benefit for the mother exceeds the possible risk to the fetus.
Piperacillin in low concentrations is secreted with breast milk; the isolation of tazobactam in milk has not been studied. If it is necessary to use the drug during lactation, it is necessary to stop breastfeeding during the treatment.

Dosing and Administration:Intravenously slowly run for at least 3-5 minutes or drip for 20-30 minutes.
The duration of treatment is determined by the severity of the infectious process and the dynamics of clinical and bacteriological indicators.
Adults and children over 12 years with normal renal function
The recommended dose of the drug, which is prescribed every 8 hours, is 4.5 g (4 g piperacillin / 0.5 g tazobactam).
The total daily dose depends on the severity and localization of the infection and can vary from 2.25 g (2 g piperacillin / 0.25 g tazobactam) to 4.5 g (4 g piperacillin / 0.5 g tazobactam) drug administered every 6 or 8 ocloc'k.
Children aged from 2 to 12 years.
For neutropenia:
In patients with normal kidney function and body weight less than 50 kg with a fever resulting from neutropenia, the dose is 90 mg (80 mg piperacillin / 10 mg tazobactam) per kilogram of body weight, administered every 6 hours in combination with the appropriate dose aminoglycoside.
In children with a body weight of more than 50 kg, the dose corresponds to an adult, and is administered in combination with aminoglycosides.
With intra-abdominal infection: In children with a body weight of up to 40 kg and normal renal function, the recommended dose is 112.5 mg / kg (100 mg piperacillin / 12.5 mg tazobactam) every 8 hours.
Children with a body weight of more than 40 kg and normal kidney function are given the same dose as an adult, i.e. 4.5 g of the drug (4 g piperacillin / 0.5 g tazobactam) every 8 hours.
Treatment should be conducted for at least 5 days and no more than 14 days, given that the administration of the drug is continued for at least 48 hours after the disappearance of clinical signs of infection.
Impaired renal function
Patients with renal insufficiency or a patient on hemodialysis, dose and frequency of administration should be adjusted for the degree of impaired renal function.
Recommended doses of the drug for adults and children (body weight> 50 kg) with renal failure

Creatinine clearance (ml / min) - Recommended piperazillin / tazobactam dosage:
> 40 - No dose adjustments required
20-40 - 12 g / 1.5 g / day 4 g / 0.5 g every 8 hours
<20 - 8 g / 1 g / day 4 g / 0.5 g every 12 hours
For patients on hemodialysis, the maximum daily dose is 8 g / 1 g of piperacillin / tazobactam. In addition, since 30-50% piperacillin is withdrawn from the hemodialysis during 4 hours, one additional dose of 2 g / 0.25 g piperacillin / tazobactam should be given after each dialysis session.
Children 2-12 years with renal insufficiency:
The pharmacokinetics of piperacillin / tazobactam in children with renal insufficiency have not been studied. For children aged 2-12 years with renal insufficiency, it is recommended to adjust the dose as follows:
Recommended doses of the drug for children / body weight <50 kg) with renal failure:
Creatinine clearance - Recommended piperazillin / tazobactam dosage
> 50 ml / min - 112.5 mg / kg (100 mg piperacillin / 12.5 mg tazobactam) every 8 hours;
<50 ml / min - 78.75 mg / kg (70 mg piperacillin / 8.75 mg tazobactam) every 8 hours.
Such a change in dose is only indicative. Each patient should be monitored for the timely detection of signs of an overdose. It is necessary to adjust the dose of the drug and the interval between the administration of the next dose accordingly.
There is no need for dose adjustments for liver function disorders.
In elderly patients, dose adjustment is necessary only if there is a violation of kidney function.
Method of solution preparation.
The preparation is dissolved in one of the following solvents in accordance with the indicated volumes. Vial Rotate in a circular motion until the content is completely dissolved (with constant rotation, usually for 5-10 minutes). The prepared solution is a colorless or pale yellow liquid.
Dosage / vial (piperacillin / tazobactam) - Required volume of solvent:
2.25 g (2 g / 250 mg) 10 ml;
4.50 g (4 g / 500 mg) - 20 ml;
Solvents compatible with the preparation 0.9% solution of sodium chloride; sterile water for injections; 5% dextrose solution.
Then the prepared solution can be diluted to the volume required for intravenous administration (for example, from 50 ml to 150 ml) by one of the following compatible solvents: 0.9% sodium chloride solution; sterile water for injections (the maximum recommended volume is 50 ml); 5% dextrose solution.

Side effects:Allergic reactions: urticaria, skin itch, rash, bullous dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactic / anaphylactoid reactions (including anaphylactic shock).
From the digestive system: diarrhea, nausea, vomiting, constipation, indigestion, jaundice, stomatitis, abdominal pain, pseudomembranous colitis, hepatitis.
From the hematopoiesis: leukopenia, neutropenia, thrombocytopenia, anemia, bleeding (including purpura, nasal bleeding, increased bleeding time),hemolytic anemia, agranulocytosis, false positive Coombs direct test, pancytopenia, increased activated partial thromboplastin time, increased prothrombin time, thrombocytosis.
From the urinary system: interstitial nephritis, kidney failure.
From the nervous system: headache, insomnia, cramps.
From the cardiovascular system: lowering blood pressure, "hot flashes".
Laboratory indicators: hypoalbuminemia, hypoglycemia, hypoproteinemia, hypokalemia, eosinophilia, increased activity of "hepatic" transaminases (alanine aminotransferase, aspartate aminotransferase), hyperbilirubinemia, increased activity of alkaline phosphatase, gamma glutamyltransferase, increased serum creatinine and urea concentration.
Local reactions: phlebitis, thrombophlebitis, hyperthermia at the injection site, hyperemia and compaction at the site of administration.
Other: fungal superinfections, fever, arthralgia.

Overdose:Symptoms of overdose are nausea, vomiting, diarrhea, increased neuromuscular excitability and convulsions.Depending on the clinical manifestations, symptomatic treatment is prescribed. To reduce high concentrations of piperacillin or tazobactam in the serum, hemodialysis can be prescribed.

Interaction:The combined use of the drug with probenecid increases the half-life and decreases the renal clearance of both piperacillin and tazobactam, but the maximum plasma concentrations of both drugs remain unchanged.
The simultaneous use of the drug and vecuronium bromide can lead to a longer neuromuscular blockade caused by the latter (a similar effect can be observed with a combination of piperacillin with other nondepolarizing muscle relaxants).
With the simultaneous use of high doses of heparin, indirect anticoagulants or other drugs that affect the blood clotting system, including the function of platelets, it is necessary to more often monitor the state of the blood coagulation system.
Piperacillin may delay the excretion of methotrexate (in order to avoid a toxic effect, it is necessary to control the concentration of methotrexate in the blood serum).
Pharmaceutical compatibility with other drugs.
The drug should not be mixed in one syringe or dropper with other medications including aminoglycosides. When used in conjunction with other antibiotics, drugs should be administered separately; most preferably the administration of piperacillin / tazobactam and aminoglycoside is delineated in time.
The drug should not be used in conjunction with solutions containing sodium hydrogen carbonate and add to blood products or albumin hydrolysates.

Special instructions:Before starting treatment, the patient should be interviewed in detail in order to identify possible hypersensitivity reactions to penicillins, cephalosporins or other allergens. Severe allergic reactions are more likely to develop in patients with increased sensitivity to several allergens. Such reactions require the cessation of the administration of the drug and the appointment of epinephrine (adrenaline) and other emergency measures.
The pseudomembranous colitis caused by antibiotics can be manifested by severe, persistent diarrhea, which poses a threat to life. Pseudomembranous colitis can develop both during antibiotic therapy and after its completion.In such cases, the drug should be discontinued immediately and appropriate therapy should be prescribed (eg, by mouth metronidazole, vancomycin). Preparations that inhibit intestinal motility are contraindicated.
In the treatment, especially long-term, the development of leukopenia and neutropenia, so you need to periodically monitor the peripheral blood.
In a number of cases (most often in patients with renal insufficiency), the appearance of increased bleeding and concomitant changes in the laboratory parameters of the blood coagulation system (clotting time, platelet aggregation and prothrombin time) is likely. When bleeding occurs, it is necessary to cancel the treatment with the drug and prescribe the appropriate therapy.
It should be borne in mind the possibility of the emergence of resistant microorganisms, which can cause superinfection, especially with a long course of treatment.
This preparation contains 2.79 mEq. (64 mg) of sodium per gram of piperacillin, which can lead to a general increase in sodium intake. In patients with hypokalemia or taking drugs that promote the excretion of potassium,during the treatment may develop hypokalemia (it is necessary to regularly check the content of electrolytes in the blood serum).
No experience in children under 2 years of age.
During the use of the drug, a false positive result can be obtained for glucose in the urine using a method based on the reduction of copper ions. Therefore, it is recommended to carry out a test based on enzymatic oxidation of glucose (glucose oxidase method).

Form release / dosage:Powder for the preparation of a solution for intravenous administration of 2g + 0.25g, 4g + 0.5g.

Packaging:By 2.25 or 4.5 grams of a mixture of active ingredients in a vial of colorless glass, corked with a cork of gray chlorobutyl rubber, coated with an aluminum cap. 1 bottle with instructions for use in a cardboard box.
For hospitals:
10, 12, 25, 48 or 100 vials together with an equal number of instructions for use in a cardboard box.

Storage conditions:In the dark place at a temperature of no higher than 25FROM . Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002493/10

Date of registration:26.03.2010

The owner of the registration certificate:Jodas Expo Pvt.LtdJodas Expo Pvt.Ltd India

Manufacturer: & nbsp

JODAS EXPOIM, Pvt. Ltd. India

Representation: & nbspJodas Expoim, Open CompanyJodas Expoim, Open Company

Information update date: & nbsp26.03.2010

Illustrated instructions

Instructions

Tacillin J (Tacillin J)