Piperacillin + Tazobactam-Alkem - instructions for use, dose, side effects, contraindications

Composition:One bottle contains:
A mixture of piperacillin sodium and tazobactam sodium in the ratio (8: 1) 5025 mg.
active ingredients: piperacillin (in the form of piperacillin sodium) 4000 mg, tazobactam (in the form of sodium 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:Combined antibacterial drug. Contains piperacillin - a semisynthetic broad-spectrum antibiotic and tazobactam - the inhibitor of most beta-lactamases; including plasmid and chromosomal enzymes. Most strains of microorganisms resistant to piperacillin and producing beta-lactamases are sensitive to the drug.
Active in relation to:
aerobic gram-matic bacteria: Escherichia coli, Citrobacter spp. (including Citrobacter freundii, Citrobacter diversus), Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Enterobacter spp. (including Enterobacter cloacae, Enterobacter aerogenes), Proteus spp. (including Proteus mirabilis, Proteus vulgaris), Providencia spp., Plesiomonas, shigelloides, Morganella morganii, Serratia spp. (including Serratia marcescens, Serratia liquifaciens), Salmonella spp., Shigella spp., Pseudomonas aeruginosa (only piperacillin susceptible strains) and other Pseudomonas spp. (including Pseudomonas cepacia, Pseudomonas fluorescens), Xanthamonas maltophilia, Neisseria spp. (including Neisseria meningitidis, Neisseria gonorrhoeae), Moraxella spp. (including Branhamella catarrhalis), Acinetobacter spp., Haemophilus spp. . (including Haemophilus influenzae, Haemophilus parainfluenzae), Pasteurella multocida, Yersinia spp., Campylobacter spp., Gardnerella vaginalis;
aerobic Gram-positive bacteria: Streptococcus spp. (Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus bovis, Streptococcus spp., Group viridans (C and G)); Enterococcus spp. (Enterococcus faecalis, Enterococcus faecium), Staphylococcus spp. (Staphylococcus aureus methicillin susceptible strains, Staphylococcus epidermidis, Staphylococcus saprophyticus), Listeria monocytogenes, Nocardia spp .;
anaerobic bacteria: Bacteroides spp. (Bacteroides fragilis, Bacteroides disiens, Bacteroides capillosus, Bacteroides melaninogenicus, Bacteroides oralis, Bacteroides distasonis, Bacteroides uniformis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides bivius, Bacteroides asaccharolyticus), Fusobacterium spp., Clostridium spp. (including Clostridium perfringens, Clostridium difficile), Peptostreptococcus spp., Eubacter spp .; Veillonella spp., Actinomyces spp.

Pharmacokinetics:All the pharmacokinetics in the separate and combined use of piperacillin and tazobactam were identical.
- suction: The maximum concentration (Stach) is reached immediately after intravenous administration.
- distribution: Binding to plasma proteins - 20-30%. Piperacillin well penetrates into the tissues and body fluids, including the gastrointestinal tract (GIT), bile ducts, lungs, bones and the prostate gland. Excreted in breast milk.
- metabolism: Piperacillin metabolized in a weakly active metabolite, tazobactam - in an inactive metabolite.
- excretion: It is excreted by the kidneys through glomerular filtration and tubular secretion: piperacillin - 68% unchanged, tazobactam - 80% unchanged and a small amount - in the form of a metabolite. The rest of the amount is excreted with bile. The half-life period (Tl / 2) of piperacillin and tazobactam is independent of the dose and duration of the infusion and ranges from 0.7 to 1.2 hours. Piperacillin slightly reduces the rate of excretion of tazobactam.
Pharmacokinetics in special clinical cases
In chronic renal insufficiency, T1 / 2 increases: when creatinine clearance (KK) is less than 20 ml / min T1 / 2 piperazillina increases 2 times, T1 / 2 tazobactam - 4 times. By means of hemodialysis, 30-50% of the administered piperazillin dose and an additional 5% in the form of the metabolite of tazobactam are excreted. With peritoneal dialysis, 6% piperacillin and 21% tazobactam are excreted, and 18% is metabolized by tazobactam.
When violations of liver function T1 / 2 piperazillina increased by 25%, T1 / 2 tazobactam - by 18% (with significant adjustment of the dose is not required).

Indications:Infectious-inflammatory diseases caused by microorganisms sensitive to piperacillin / tazobactam.
for adults and children over 12 years of age:
- Lower respiratory tract infection;
- abdominal infections - peritonitis, pelvioperitonitis, cholangitis, gallbladder empyema, appendicitis (including, complicated by abscess or perforation) and others;
- intra-abdominal infections - peritonitis, pelvioperitonitis, cholangitis, gallbladder empyema, appendicitis (including complicated by abscess or perforation);
- Urinary tract infections (including complicated ones) - pyelonephritis, cystitis, prostatitis, epididymitis, gonorrhea, endometritis, vulvovaginitis, postpartum endometritis and adnexitis;
- infection of bones, joints;
- infections of the skin and soft tissues (including, cellulitis, abscess, infected trophic ulcers);
- septicemia;
- bacterial infection in patients with neutropenia in combination with aminoglycosides;
- Mixed infections caused by aerobic and anaerobic microorganisms.
for children (age 2-12 years):
- intra-abdominal infections - peritonitis, pelvioperitonitis, cholangitis, gallbladder empyema, appendicitis (including complicated by abscess or perforation);
- bacterial infection in patients with neutropenia in combination with aminoglycosides.

Contraindications:Hypersensitivity to piperacillin / tazobactam (including penicillins, cephalosporins, other inhibitors of beta-lactam antibiotics), children under 2 years.

Carefully:Severe bleeding (including history), cystic fibrosis (increased risk of hyperthermia and skin rash), pseudomembranous colitis, chronic renal failure - KK less than 20 ml / min, hypokalemia; patients on hemodialysis; simultaneous use of high doses of anticoagulants; pregnancy, lactation, children's age.

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. The use of the drug during pregnancy is possible only in the event that,If the expected benefit for the mother exceeds the possible risk to the fetus. Piperacillin in low concentrations is secreted with breast milk. The drug can be prescribed for women who are breastfeeding if the expected benefit to the mother exceeds the possible risk to the fetus, or breastfeeding should be stopped for the duration of treatment.

Dosing and Administration:Intravenously slowly struyno (for at least 3-5 minutes) or drip (for at least 20-30 minutes).
Adults and children over 12 years with normal renal function
The recommended average daily dose is 12 g of piperacillin and 1.5 g of tazobactam: 4.5 g (4 g piperacillin / 0.5 g tazobactam) every 8 hours.
In infections caused by Pseudomonas aeruginosa, additional assignment of aminoglycosides is indicated.
In chronic renal failure daily doses of piperacillin / tazobactam for adults and children (body weight over 50 kg) are adjusted depending on KK: at KK more than 40 ml / min - dose adjustment is not required; KK 20-40 ml / min - 12 g / 1.5 g / day (4 g / 0.5 g every 8 hours), with KK less than 20 ml / min - 8 g / 1 g / day (4 g each / 0.5 g every 12 hours).
For patients on hemodialysis, the maximum dose is 8 g of piperacillin 1 g of tazobactam.Since during the hemodialysis 30-50% of piperacillin is washed out after 4 hours, one additional dose of 2 g of piperacillin and 0.25 g of tazobactam should be prescribed after each dialysis session.
The course of treatment - usually 7-10 days, according to the indications can be increased to 14 days;
Children from 2 to 12 years old
With neutropenia: for children with normal renal function and body weight less than 50 kg, the dose is 90 mg / kg (80 mg piperacillin / 10 mg tazobactam) every 6 hours with a suitable dose of 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. In combination therapy with aminoglycosides, the daily dose should not exceed 4.5 g (4 g piperacillin / 0.5 g tazobactam) every 6 hours.
With intra-abdominal infection: in children with normal renal function and body weight less than 40 kg, the dose is 112.5 mg / kg (100 mg piperacillin / 12.5 mg tazobactam) every 8 hours, the daily dose should not exceed 4.5 g (4 g piperacillin and 0.5 g of tazobactam) every 8 hours. Children with a body weight of more than 40 kg and normal kidney function are given the same dose as adults.

In chronic renal failure daily doses of piperacillin / tazobactam for children 2 to 12 years of age (body weight less than 50 kg) are adjusted depending on the KK: at KK more than 50 ml / min - 112.5 mg / kg (100 mg piperacillin / 12.5 mg tazobactam) every 8 hours, KK 50 ml / min and less - 78.75 mg / kg (70 mg piperacillin / 8,75 mg tazobactam) every 8 hours).
No dosage adjustment required with a violation of the liver.
In elderly patients, dose adjustment is necessary only if there is a violation of kidney function.
Preparation of a solution for intravenous administration
The solution for intravenous administration is prepared under aseptic conditions.
To prepare the solution for intravenous administration, 0.9%, sodium chloride solution, 5% dextrose solution, sterile water for injection are used as solvents. For intravenous administration, a bottle containing 4.5 g of the drug is diluted with 20 ml of one of the above solutions. Stir until completely dissolved. To reduce the risk of microbial contamination, the solution is used immediately after preparation.
The prepared solution can be diluted to the desired volume for intravenous administration (eg from 50 ml to 150 ml) by one of the below listed compatible solvents: 0.9% sodium chloride solution, 5% dextrose solution, sterile water for injections (the maximum recommended volume is 50 ml).
Unused solution can be stored at a temperature of 20-25 ° C for not more than 24 hours, and also in a refrigerator at a temperature of 2-8 0C for not more than 48 hours. After preparing the solution, the vials should not be frozen.

Side effects:Very frequent -> 10%; frequent -> 1% and <10%; not frequent -> 0,1% and <1%; rare -> 0.01% and <0.1%; very rare -0.01%.
From the cardiovascular system: infrequently - arterial hypotension, phlebitis, thrombophlebitis; rarely - the "tides" of blood to the skin of the face.
From the nervous system: infrequently - headache, insomnia; rarely convulsions.
From the digestive system: often - diarrhea, nausea, vomiting; infrequently - constipation, indigestion, jaundice, stomatitis; rarely - abdominal pain, pseudomembranous colitis, hepatitis.
From the side of metabolism: very rarely - hypoalbuminemia, hypoglycemia, hypoproteinemia, hypokalemia.
From the hematopoiesis: infrequently - leukopenia, neutropenia, thrombocytopenia; rarely anemia, bleeding (including purpura, epistaxis, increased bleeding time), eosinophilia, hemolytic anemia; very rarely - agranulocytosis, positive direct Coombs test, pancytopenia, increased partial thromboplastin time,increased prothrombin time, thrombocytosis.
From the urinary system: rarely - interstitial nephritis, kidney failure.
Allergic reactions: often - a rash; infrequently - itching, hives; rarely-bullous dermatitis, erythema multiforme; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactic / anaphylactoid reactions (including anaphylactic shock).
Laboratory indicators: infrequently - increased activity of "hepatic" transaminases (alanine aminotransferase, aspartate aminotransferase), increased serum creatinine and urea concentration; rarely - hyperbilirubinemia, increased activity of alkaline phosphatase, increased activity of gamma-glutamyltransferase,
Other: infrequently - fungal superinfections, fever, hyperemia and compaction at the injection site; rarely - arthralgia.

Overdose:Symptoms: nausea, vomiting diarrhea, increased neuromuscular excitability, convulsions.
Treatment: symptomatic, including the appointment of antiepileptic drugs (including diazepam or barbiturates), hemodialysis or peritoneal dialysis.Specific antidotes are not known.

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).
When used simultaneously with heparin, oral anticoagulants and other drugs that affect the blood coagulation 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.
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 to identify possible hypersensitivity reactions to penicillins, cephalosporins or other allergens. Severe allergic reactions are more likely to develop in patients with hypersensitivity to several allergens. Such reactions require discontinuation, administration of the drug and the appointment of epinephrine (adrenaline) and other emergency interventions.
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 (for example, vancomycin, metronidazole inside). 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), there appears to be increased bleeding and concomitant, changes in the laboratory parameters of the blood coagulation system (clotting time, platelet aggregation and prothrombin time). At occurrence, bleedings it is necessary to cancel treatment by a preparation and to appoint or nominate corresponding 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.
With prolonged treatment, it is necessary to periodically monitor the function of the kidneys, liver.
Use in Pediatrics: Safety and efficacy in children under 2 years of age have not been investigated. ;

Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles and when engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions due to the risk of seizures.

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

Packaging:For 4 g of piperacillin and 0.5 g of tazobactam, in the form of a mixture of piperacillin sodium and tazobactam sodium in a colorless transparent 30 ml glass bottle of Type I glass, sealed with a butyl rubber stopper of gray color and covered with an aluminum flip-off cap with a tear a cover of red color.
1 bottle with the drug, along with instructions for use, is placed in a cardboard box.

Storage conditions:In a dry, the dark place at a temperature of no higher than 30 0C.
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:LP-001380

Date of registration:20.12.2011

The owner of the registration certificate:Alkem Laboratories LtdAlkem Laboratories Ltd India

Manufacturer: & nbsp

ALKEM LABORATORIES, Ltd. India

Information update date: & nbsp20.12.2011

Illustrated instructions

Instructions

Piperacillin + Tazobactam-Alkem (Piperacillin + Tazobactam-Alkem)