Polycef powder for solution for injection and infusion 1000 mg vial No. 10

Instructions for use Polycef powder for solution for injection and infusion 1000 mg vial No. 10

Composition

active ingredient: cefepime;

1 vial contains 1190 mg of cefepime hydrochloride monohydrate, equivalent to 1000 mg of cefepime;

excipient: L-arginine.

Dosage form

Powder for solution for injection or infusion.

Main physicochemical properties: white to almost white crystalline powder.

Pharmacotherapeutic group

Antibacterials for systemic use. Other beta-lactam antibiotics. Fourth generation cephalosporins. ATX code J01D E01.

Pharmacological properties

Pharmacodynamics.

Cefepime acts by inhibiting the synthesis of bacterial wall enzymes. The drug has a broad spectrum of activity against gram-positive and gram-negative bacteria, is highly resistant to hydrolysis by most beta-lactamases, has low affinity for beta-lactamases encoded by chromosomal genes, and rapidly penetrates gram-negative bacterial cells. Cefepime is active against the following microorganisms: gram-positive aerobes:

Staphylococcus aureus (including beta-lactamase producing strains); Staphylococcus epidermidis (including beta-lactamase producing strains); other staphylococcal strains, including S. hominis, S. saprophyticus; Streptococcus pyogenes (group A streptococci); Streptococcus agalactiae (group B streptococci); Streptococcus pneumoniae (including strains with intermediate resistance to penicillin - MIC from 0.1 to 1 μg / ml); other beta-hemolytic streptococci (groups C, G, F), S. bovis (group D), Viridans group streptococci.

Most strains of enterococci, such as Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to most cephalosporin antibiotics, including cefepime;

Gram-negative aerobes:

Pseudomonas srp., including P. aeruginosa, P. putida, P. stutzeri; Escherichia coli, Klebsiella srp., including K. pneumoniae, K. oxytoca, K. ozaenae; Enterobacter srp., including E. cloacae, E. aerogenes, E. sakazakii; Proteus srp., including P. mirabilis, P. vulgaris; Acinetobacter calcoaceticus (subsp. anitratus, lwoffi); Aeromonas hydrophila; Capnocytophaga srp.; Citrobacter srp., including C. diversus, C. freundii; Campylobacter jejuni; Gardnerella vaginalis; Haemophilus ducreyi; Haemophilus influenzae (including beta-lactamase-producing strains); Haemophilus parainfluenzae; Hafnia alvei; Legionella srp.; Morganella morganii; Moraxella catarrhalis (Branhamella catarrhalis) (including strains producing beta-lactamase); Neisseria gonorrhoeae (including beta-lactamase producing strains); Neisseria meningitidis; Providencia spp. (including P. retigeri, P. stuartii); Salmonella spp.; Serratia (including S. marcescens, S. liquefaciens); Shigella spp.; Yersinia enterocolitica. Cefepime is inactive against some strains of Xanthamonas maltophilia (Pseudomonas maltophilia);

anaerobes:

Bacteroides spp., including B. melaninogenicus and other oral microorganisms belonging to Bacteroides; Clostridium perfringens; Fusobacterium spp.; Mobiluncus spp.; Peptostreptococcus spp.; Veillonella spp. (cefepime is inactive against Bacteroides fragilis and Clostridium difficile).

Pharmacokinetics.

The half-life is about 2 hours. In healthy people, cumulation of the drug in the body was not observed.

Cefepime is metabolized to N-methylpyrrolidine, which is rapidly converted to N-methylpyrrolidine oxide. Total clearance is 120 ml/min. Cefepime is primarily excreted by the kidneys (mean renal clearance is 110 ml/min). Approximately 85% of the administered dose is recovered in the urine as unchanged cefepime, 1% as N-methylpyrrolidine, about 6.8% as N-methylpyrrolidine oxide, and about 2.5% as the epimer of cefepime. The binding of cefepime to plasma proteins is independent of the concentration of the drug in the serum and is less than 19%.

Cefepime is well distributed in the body and reaches therapeutic concentrations in urine, bile, peritoneal fluid, bronchial mucus, sputum, prostate, appendix, and gallbladder.

Plasma concentrations of cefepime in healthy adult males after single intravenous/intramuscular administration are shown in the table below.

Mean plasma concentrations of cefepime (μg/mL)

In patients with renal impairment, the elimination half-life of cefepime is increased. In patients with severe renal impairment undergoing dialysis, the elimination half-life is 13 hours for hemodialysis and 19 hours for peritoneal dialysis.

The pharmacokinetics of cefepime are not altered in patients with impaired hepatic function or cystic fibrosis. No dose adjustment is required for these patients.

Children.

About 60.4 (± 30.4) % of the administered dose of cefepime is excreted unchanged in the urine, the renal clearance is 2.0 (± 1.1) ml/min/kg. After intramuscular administration, the maximum concentration of cefepime in the blood plasma at steady state is on average 68 μg/ml after 0.75 hours. After 8 hours after intramuscular administration, the concentration of cefepime in the blood plasma is 6 μg/ml. The absolute bioavailability after intramuscular injection of cefepime is on average 82%. The age and gender of the patients do not affect the clearance of the drug.

Drug concentrations in cerebrospinal fluid (CSF) and blood plasma

in children with bacterial meningitis

* age from 3.1 months to 12 years with a standard deviation in age of ± 3 years.

The drug dose was 50 mg/kg body weight intravenously over 5-20 minutes every 8 hours. Plasma and CSF concentrations were determined at the end of the administration on the 2nd or 3rd day of drug administration.

Indication

Adults.

Infections caused by microflora sensitive to the drug:

• respiratory tract, including pneumonia, bronchitis;
• skin and subcutaneous tissue;
• intra-abdominal infections, including peritonitis and biliary tract infections;
• urinary tract infections, including pyelonephritis;
• gynecological;
• septicemia.

Empirical therapy of patients with neutropenic fever.

Prevention of postoperative complications in intra-abdominal surgery.

Children.

• Pneumonia;
• urinary tract infections, including pyelonephritis;
• infections of the skin and subcutaneous tissue;
• septicemia;
• empirical therapy of patients with neutropenic fever;
• bacterial meningitis.

Contraindication

Hypersensitivity to cefepime or L-arginine;

· hypersensitivity to cephalosporin antibiotics, penicillins or other beta-lactam antibiotics.

Interaction with other medicinal products and other types of interactions

Cefepime solution is compatible with the following parenteral solutions: 0.9% sodium chloride solution, 5% or 10% glucose solutions, 6 M sodium lactate solution for injection, Ringer's lactate solution with 5% dextrose solution for injection.

Given the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics, high doses of these drugs should be used concomitantly with cefepime under renal function monitoring.

The use of cephalosporins with diuretics (e.g., furosemide) leads to increased nephrotoxicity of the former.

To avoid possible drug interactions with other drugs, cefepime solution (like most other beta-lactam antibiotics) should not be administered simultaneously with solutions of metronidazole, vancomycin, gentamicin, tobramycin sulfate and netilmicin sulfate. In the case of prescribing Policef with these drugs, each antibacterial agent must be administered separately.

Concomitant treatment with bacteriostatic antibiotics may affect the action of beta-lactam antibiotics.

Impact on laboratory test results.

Cefepime may cause a false-positive reaction for glucose in urine when Benedict's reagent is used. It is recommended to use glucose tests based on the enzymatic glucose oxidation reaction.

Application features

Hypersensitivity.

Before using the drug, it is necessary to find out whether the patient has previously had immediate-type hypersensitivity reactions to cefepime, cephalosporins, penicillins or other beta-lactam antibiotics.

Cefepime should be used with caution in patients with asthma or allergic diathesis. The patient's condition should be closely monitored during the first administration. If an allergic reaction occurs, treatment should be discontinued immediately.

Antibiotics should be administered with caution to all patients with any form of allergy, especially to drugs. If an allergic reaction occurs, the drug should be discontinued. Serious immediate-type hypersensitivity reactions may require the use of adrenaline and other forms of therapy.

It is unlikely that the use of cefepime in the absence of a proven or suspected bacterial infection or its prophylactic use will be beneficial, but it may increase the risk of the emergence of bacteria resistant to this drug. Prolonged use of cefepime (as with other antibiotics) may lead to the development of superinfection. The patient's condition should be re-evaluated. In the event of the development of superinfection, appropriate treatment measures should be initiated.

Kidney failure.

Patients with impaired renal function (creatinine clearance

The following serious adverse reactions have been reported in post-marketing experience: reversible encephalopathy (impaired consciousness including confusion, hallucinations, stupor and coma), myoclonus, convulsions (including status epilepticus) and/or renal failure. The majority of cases occurred in patients with renal insufficiency receiving doses of cefepime in excess of the recommended dose. In most cases, the symptoms of nephrotoxicity were reversible and resolved after discontinuation of cefepime and/or haemodialysis.

Clostridium difficile associated diarrhea.

Antibiotic-associated diarrhea and antibiotic-associated colitis, including pseudomembranous colitis and Clostridium difficile-associated diarrhea, have been reported with the use of nearly all antibacterial agents, including cefepime, and may range in severity from mild diarrhea to fatal colitis. Therefore, it is important to consider this diagnosis in patients who develop serious diarrhea during or after the use of cefepime. If antibiotic-associated diarrhea or antibiotic-associated colitis is suspected or confirmed, antibacterial agents, including cefepime, should be discontinued and appropriate therapeutic measures should be initiated immediately. Medicinal products that inhibit peristalsis are contraindicated in these patients.

Elderly patients.

Cefepime is known to be largely excreted by the kidneys and the risk of toxic reactions to this drug may be higher in patients with renal insufficiency. Since elderly patients are more likely to have decreased renal function, caution should be exercised in dose selection and renal function should be monitored. Serological testing.

Cephalosporins tend to be absorbed on the surface of red blood cells and react with antibodies directed against the drugs, resulting in a positive Coombs test. A positive Coombs test in the absence of hemolysis has been described in patients receiving cefepime twice daily.

A false-positive result may occur when performing a urine test for glucosuria. For this reason, determination of glucose in urine should be performed by glucose oxidase methods during treatment with the drug.

It is necessary to monitor prothrombin time.

L-arginine has been shown to alter glucose metabolism and simultaneously increase serum potassium levels at doses 33 times the maximum recommended dose of cefepime. Effects at lower doses are currently unknown.

Use during pregnancy or breastfeeding

Animal studies have shown no effect on reproductive function and no harmful effects on the fetus. However, adequate and well-controlled studies in pregnant women have not been conducted, so the drug should be prescribed during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.

Cefepime passes into breast milk in very small amounts, so breastfeeding should be discontinued during treatment.

Ability to influence reaction speed when driving vehicles or other mechanisms

Not studied. If dizziness, hallucinations, confusion, or other side effects from the nervous system occur that may affect reaction time, you should refrain from driving or using other mechanisms.

Method of administration and doses

The dose and route of administration may vary depending on the susceptibility, site and type of microorganism, the severity of the infection, and the age and functional status of the patient. Adults should usually be given 1 g intravenously/intramuscularly every 12 hours. The course of treatment is 7-10 days. Severe infections may require longer treatment. The dosage recommendations for Policef for adults are given in Table 1.

Table 1

Patients over 65 years of age with normal renal function do not require dose adjustment. Prevention of possible infection during surgical operations. 2 g of the drug should be administered intravenously drip over 30 minutes 1 hour before the start of the surgical operation. After the end of the administration, additionally administer 500 mg of metronidazole intravenously. Metronidazole solution should not be administered simultaneously with Polycef. In case of simultaneous use, each antibiotic should be administered in separate systems. When using one system for two drugs, the system should be flushed before metronidazole infusion.

During prolonged (more than 12 hours) surgical operations, it is recommended to repeat the same dose of Policef 12 hours after the first dose, followed by metronidazole.

Children aged 1 to 2 months. Use only if absolutely necessary. Administer at a dose of 30 mg/kg body weight every 12 or 8 hours. Children weighing up to 40 kg receiving treatment with Polycef should be monitored closely.

Children from 2 months of age. The maximum dose for children should not exceed the recommended dose for adults. For children weighing up to 40 kg, the recommended dose is 50 mg/kg every 12 hours (for patients with febrile neutropenia and bacterial meningitis, every 8 hours). The duration of therapy is 7-10 days; severe infections may require longer treatment.

Children weighing 40 kg or more should be prescribed Policef in the same way as adults.

Renal impairment. In patients with impaired renal function (creatinine clearance less than 30 ml/min), the drug administration regimen should be adjusted. The initial dose of Polycef is similar to that for patients with unchanged renal function. The recommended maintenance doses of Polycef are given in Table 2.

Table 2

If only the serum creatinine concentration is known, creatinine clearance can be determined using the formula below.

Men:

body weight (kg) ´ (140 - age)

creatinine clearance (ml/min) = ---------------------------------------------------.

72 ´ serum creatinine (mg/dL)

Women:

creatinine clearance (ml/min) = above value ´ 0.85.

During hemodialysis, approximately 68% of the administered dose of the drug is removed from the body within 3 hours. After each hemodialysis session, a repeat dose similar to the initial dose should be administered. During continuous ambulatory peritoneal dialysis, the drug can be used in normal recommended doses depending on the severity of the infection, with an interval between single doses of 48 hours.

In cases of renal impairment in children, a dose reduction or prolongation of the interval between administrations is recommended, as indicated in Table 2.

Calculation of creatinine clearance in children:

0.55 ´ height (cm)

creatinine clearance (ml/min/1.73 m2) = ---------------------------------

serum creatinine (mg/dL)

or

0.52 ´ height (cm)

creatinine clearance (ml/min/1.73 m2) = ------------------------------------------ - 3.6.

serum creatinine (mg/dL)

Administration of the drug.

Polycef should be administered intravenously or deeply intramuscularly into a large muscle mass (for example, into the upper outer quadrant of the gluteal muscle).

Intravenous administration. This route of administration should preferably be used in patients with severe, life-threatening infections.

For intravenous administration, dissolve Polycef in 5 or 10 ml of sterile water for injection, 5% glucose solution or 0.9% sodium chloride solution, as indicated in Table 3. The prepared solution should be administered slowly by jet over 3-5 minutes or drip through an intravenous administration system.

Intramuscular administration. Dissolve Polycef in sterile water for injection, 0.9% sodium chloride solution, 5% glucose solution for injection, bacteriostatic water for injection with paraben or benzyl alcohol in the concentrations indicated in Table 3. As with other drugs used parenterally, ready-made solutions of the drug should be checked for the absence of mechanical inclusions before administration.

Table 3

Children.

The medicine should be used in children over 1 month of age.

Overdose

Symptoms: in case of significant excess of the recommended doses, especially in patients with impaired renal function, the manifestations of side effects are aggravated. Symptoms of overdose include encephalopathy, accompanied by hallucinations, impaired consciousness, stupor, coma, myoclonus, epileptiform seizures, neuromuscular excitability.

Treatment. The drug should be discontinued and symptomatic therapy should be administered. Hemodialysis accelerates the elimination of cefepime from the body; peritoneal dialysis is ineffective. Severe immediate-type allergic reactions require the use of adrenaline and other forms of intensive care.

Adverse reactions

Adverse reactions are rare.

Infections: candidiasis, vaginitis, genital itching, pseudomembranous colitis, other superinfections.

From the respiratory system, chest organs and mediastinum: respiratory disorders, cough, sore throat, shortness of breath.

Gastrointestinal: nausea, vomiting, oral candidiasis, diarrhea, colitis, constipation, abdominal pain, dyspepsia, change in taste.

Liver and biliary tract disorders: hepatitis, cholestatic jaundice.

Renal and urinary disorders: renal failure.

Nervous system: dizziness, headache, anxiety, insomnia, paresthesia, confusion/loss of consciousness, convulsions/epileptiform seizures, myoclonus, encephalopathy, hallucinations, stupor, coma.

Cardiovascular system: tachycardia, vasodilation, pain in the heart area.

From the blood and lymphatic system: anemia, eosinophilia, transient leukopenia, neutropenia, agranulocytosis, thrombocytopenia.

Immune system disorders: hypersensitivity reactions, including anaphylaxis, anaphylactic shock, angioedema.

Skin and subcutaneous tissue disorders: skin rash, pruritus, urticaria. General disorders and administration site conditions: fever, sweating, chest/back pain, asthenia, injection site changes including inflammation, phlebitis, pain. Laboratory parameters: increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin in plasma, increased prothrombin time or partial thromboplastin time (PTT) and positive Coombs test without hemolysis, transient increase in blood urea nitrogen and/or serum creatinine, false positive reaction to glucose in urine. In addition to the above-mentioned adverse reactions, adverse reactions typical of cephalosporin antibiotics are possible: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, toxic nephropathy, aplastic anemia, hemolytic anemia, bleeding, liver dysfunction, cholestasis, pancytopenia. Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Expiration date

30 months.

Storage conditions

Store in the original packaging to protect from light at a temperature not exceeding 30 ° C. Keep out of the reach of children.

Incompatibility.

To avoid possible drug interactions, Polycef (like most other beta-lactam antibiotics) should not be administered in the same syringe with metronidazole, vancomycin, gentamicin, tobramycin sulfate and netilmicin sulfate. In the case of prescribing Polycef with the above-mentioned drugs, each antibacterial agent should be administered separately.

Do not mix in the same container with other medicines. Use the solvents specified in the section "Method of administration and dosage".

Packaging

1000 mg of powder in a vial; 10 vials in a cardboard box.

Vacation category

According to the recipe.

Producer

АСС DOBFAR S.P.A.

Location of the manufacturer and address of its place of business.

VIA ALESSANDRO FLEMING, 2, VERONA (VR), 37135, Italy.