Cefotrin powder for solution for injection 1 g bottle 20 ml with solvent in ampoules 10 ml No. 1

Instructions Cefotrin powder for solution for injection 1 g bottle 20 ml with solvent in ampoules 10 ml No. 1

Composition

active ingredient: cefepime hydrochloride USP equivalent to cefepime;

1 vial contains cefepime hydrochloride USP equivalent to cefepime - 1 g;

excipient: L-arginine.

Dosage form

Powder for solution for injection.

Main physicochemical properties: white to light yellow powder.

Pharmacotherapeutic group

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

Pharmacological properties

Pharmacodynamics

Cefepime inhibits the synthesis of bacterial cell wall enzymes and has a broad spectrum of activity against a variety of Gram-positive and Gram-negative bacteria. Cefepime is highly resistant to hydrolysis by most β-lactamases, has low affinity for β-lactamases encoded by chromosomal genes, and rapidly penetrates Gram-negative bacterial cells.

Cefepime is active against the following microorganisms:

gram-positive aerobes: Staphylococcus aureus and Staphylococcus epidermidis (including their β-lactamase-producing strains); other strains of staphylococci, 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 β-hemolytic streptococci (groups C, G, F), S. bovis (group D), Viridans group streptococci. Most strains of enterococci, for example, Enterococcus faecalis, and methicillin-resistant staphylococci, are resistant to most cephalosporin antibiotics, including cefepime; gram-negative aerobes: Pseudomonas spp., including P. aeruginosa, P. putida, P. stutzeri; Escherichia coli, Klebsiella spp., including K. pneumoniae, K. oxytoca, K. ozaenae; Enterobacter spp., including E. cloacae, E. aerogenes, E. sakazakii; Proteus spp., including P. mirabilis, P. vulgaris; Acinetobacter calcoaceticus (subsp. anitratus, lwoffi); Aeromonas hydrophila; Capnocytophaga spp.; Citrobacter spp., including C. diversus, C. freundii; Campylobacter jejuni; Gardnerella vaginalis; Haemophilus ducreyi; H. influenzae (including β-lactamase-producing strains); H. parainfluenzae; Hafnia alvei; Legionella spp.; Morganella morganii; Moraxella catarrhalis (Branhamella catarrhalis) (including β-lactamase-producing strains); Neisseria gonorrhoeae (including β-lactamase-producing strains); N. meningitidis; Pantoea agglomerans (known as Enterobacter agglomerans); Providencia spp. (including P. rettgeri, P. stuartii); Salmonella spp.; Serratia (including S. marcescens, S. liquefaciens); Shigella spp.; Yersinia enterocolitica. Cefepime is inactive against many strains of Xanthomonas maltophilia and Pseudomonas maltophilia; anaerobes: Bacteroides spp., including B. melaninogenicus and other oral microorganisms belonging to the Bacteroides; Clostridium perfringens; Fusobacterium spp.; Mobiluncus spp.; Peptostreptococcus spp.; Veillonella spp. Cefepime is inactive against Bacteroides fragilis and Clostridium difficile.

Pharmacokinetics

The mean plasma concentrations of cefepime in healthy adult males at various times after single intravenous and intramuscular administration are shown in the table.

Mean plasma concentrations of cefepime (μg/mL) following intravenous (IV) and intramuscular (IM) administration.

Therapeutic concentrations of cefepime are also achieved in urine, bile, peritoneal fluid, bronchial mucus, sputum, prostate, appendix, and gallbladder.

The average half-life of cefepime is about 2 hours. In healthy volunteers who received doses of up to 2 g intravenously at 8-hour intervals for 9 days, no accumulation of the drug in the body was observed.

Cefepime is metabolized to N-methylpyrrolidine, which is rapidly converted to N-methylpyrrolidine oxide. The mean total clearance is 120 ml/min. Cefepime is excreted almost exclusively by renal regulation, mainly by glomerular filtration (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 less than 19% and is independent of serum drug concentration.

Patients over 65 years of age with normal renal function do not require dose adjustment, despite the lower renal clearance compared to younger patients.

Studies in patients with varying degrees of renal impairment have shown an increase in the elimination half-life. The mean elimination half-life in patients with severe renal impairment requiring dialysis 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 necessary for these patients.

Indication

Adults.

Infections caused by microflora sensitive to the drug: respiratory tract infections, including pneumonia, bronchitis; skin, subcutaneous tissue and soft tissue infections; intra-abdominal infections, including peritonitis and biliary tract infections; gynecological infections; septicemia.

Prevention of postoperative complications in intra-abdominal surgery.

Children.

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

Contraindication

Hypersensitivity to cefepime or L-arginine, as well as to cephalosporin class antibiotics, penicillins or other β-lactam antibiotics.

Interaction with other medicinal products and other types of interactions

Renal function should be closely monitored when high doses of aminoglycosides are used concomitantly with Cefotrin because of the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics. Nephrotoxicity has been reported following concomitant use of other cephalosporins with diuretics such as furosemide.

Cefepime at concentrations from 1 to 40 mg/mL is compatible with the following parenteral solutions:

0.9% sodium chloride solution for injection; 5 and 10% glucose solutions for injection; 6M sodium lactate solution for injection, 5% glucose and 0.9% sodium chloride solution for injection; Ringer's solution with lactate and 5% glucose solution for injection.

To avoid possible drug interactions with other drugs, cefepime solutions (as well as most other b-lactam antibiotics) should not be administered simultaneously with solutions of metronidazole, vancomycin, gentamicin, tobramycin sulfate and netilmicin sulfate. If Cefotrin is prescribed with these drugs, each antibiotic should be administered separately.

Impact on laboratory test results.

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

Application features

In patients at high risk of severe infections (for example, in patients with a history of bone marrow transplantation with reduced activity, occurring against the background of malignant hemolytic pathology with severe progressive neutropenia), monotherapy may be insufficient, therefore, complex antimicrobial therapy is indicated.

It is necessary to accurately determine whether the patient has previously had immediate hypersensitivity reactions to cefepime, cephalosporins, penicillins or other b-lactam antibiotics. Antibiotics should be prescribed 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 hypersensitivity reactions may require the use of adrenaline and other forms of therapy.

Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics. Therefore, it is important to consider the possibility of this condition if diarrhea occurs during treatment with Cefotrin. Pseudomembranous colitis may range from mild diarrhea to fatal colitis. Mild colitis may resolve after discontinuation of the drug; moderate or severe cases may require specific treatment.

Use with caution in patients with digestive tract diseases, especially colitis.

During long-term treatment, it is necessary to regularly monitor the functional parameters of the liver, kidneys and hematopoiesis organs.

In patients with renal impairment (creatinine clearance < 60 mL/min), the dose of cefepime should be adjusted to compensate for the slow rate of renal elimination. Since prolonged serum concentrations of the antibiotic are possible with usual doses in patients with renal insufficiency or other conditions that may impair renal function, the maintenance dose should be reduced when cefepime is administered to such patients. The degree of renal impairment, the severity of the infection, and the susceptibility of the organisms causing the infection should be considered in determining the next dose.

With the use of cefepime, as with other drugs of this class, serious adverse reactions such as reversible encephalopathies (confusion, including clouding of consciousness), myoclonus, convulsions and/or renal failure have been observed most often in patients with renal insufficiency who received doses of the drug exceeding the recommended ones and in elderly patients with renal insufficiency on the background of the recommended doses of cefepime. Some cases occurred in patients who received doses adjusted taking into account their renal function. In most cases, symptoms of nephrotoxicity were reversible and disappeared after discontinuation of cefepime and/or after hemodialysis.

The use of antibacterial agents causes a change in the normal microflora of the large intestine and can lead to the overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is the main cause of antibiotic-associated colitis. Once the diagnosis of pseudomembranous colitis is confirmed, therapeutic measures should be taken. Pseudomembranous colitis of moderate severity may resolve after discontinuation of the drug. In cases of moderate and severe degrees, it is necessary to consider the appropriateness of the use of fluids and electrolytes, protein replenishment and the use of an antibacterial agent effective against Clostridium difficile.

Reservation.

The use of cefepime in the absence of a known or suspected bacterial infection or for prophylactic purposes is unlikely to be beneficial, but may increase the risk of the development of bacteria resistant to the drug. Prolonged use of cefepime (as with other antibiotics) may result in the development of superinfection. The patient should be re-evaluated. Appropriate measures should be taken if superinfection occurs.

Many cephalosporins, including cefepime, are associated with decreased prothrombin activity. Patients at risk include those with impaired hepatic or renal function, those who are malnourished, and those receiving prolonged antimicrobial therapy. Prothrombin should be monitored in patients at risk and vitamin K should be administered as needed.

During the period of use of cefepime, positive results of the direct Coombs test may be obtained. When performing hematological or transfusion procedures, when determining the blood group by cross-matching, when performing an antiglobulin test or during the Coombs test of newborns whose mothers received cephalosporin antibiotics before delivery, it should be taken into account that a positive Coombs test may be the result of the use of the drug.

When using lidocaine as a solvent in children, the safety information for lidocaine should be taken into account.

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.

Utilization.

Release of the medicinal product into the external environment should be minimized. The medicinal product should not be allowed to enter the sewage system or household waste.

Ability to influence reaction speed when driving vehicles or other mechanisms

Given the possible effect of the drug on the central nervous system, it is recommended to refrain from driving and working with other mechanisms while using Cefotrin.

Use during pregnancy or breastfeeding

Adequate and well-controlled studies in pregnant women have not been conducted, therefore Cefotrin 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, but breastfeeding should be discontinued during treatment with the drug.

Method of administration and doses

The usual adult dosage is 1 g, administered intravenously or intramuscularly at 12-hour intervals. The usual duration of treatment is 7-10 days; severe infections may require longer treatment.

However, the dosage and route of administration vary depending on the sensitivity of the causative microorganisms, the severity of the infection, and the functional state of the patient's kidneys.

Dosage recommendations for Cefotrin for adults are given in the table.

For the prevention of infections during surgical interventions. 60 minutes before the start of surgery, adults should be administered 2 g of the drug intravenously over 30 minutes. After that, an additional 500 mg of metronidazole should be administered intravenously. Metronidazole solutions should not be administered simultaneously with Cefotrin. The infusion system should be flushed before metronidazole is administered.

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

Renal impairment. In patients with renal impairment (creatinine clearance less than 30 ml/min), the dose of Cefotrin should be adjusted.

Recommended doses of cefepime for adults

If only the serum creatinine concentration is known, then creatinine clearance can be determined using the following formula:

Men:

body weight (kg) x (140 - age)

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

72 x serum creatinine (mg/dL)

Women:

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

During hemodialysis, approximately 68% of the dose is removed from the body within 3 hours. After each dialysis session, a repeat dose equal to the initial dose should be administered. During continuous ambulatory peritoneal dialysis, the drug can be used in the normal initial recommended doses of 500 mg, 1 or 2 g, depending on the severity of the infection, with an interval between doses of 48 hours.

Children aged 1 to 2 months. Administer only if absolutely necessary at a dose of 30 mg/kg body weight every 12 or 8 hours, depending on the severity of the infection. Children weighing up to 40 kg receiving Cefotrin treatment should be monitored closely.

For children with impaired renal function, it is recommended to reduce the dose or increase the interval between administrations.

Calculation of creatinine clearance in children:

0.55 x height (cm)

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

serum creatinine (mg/dL)

or

0.52 x height (cm)

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

serum creatinine (mg/dL)

Children from 2 months of age. The maximum dose for children should not exceed the recommended adult dose. The usual recommended dose for children weighing up to 40 kg, for complicated or uncomplicated urinary tract infections (including pyelonephritis), for uncomplicated skin infections, pneumonia, and for empirical treatment of febrile neutropenia is 50 mg/kg every 12 hours (every 8 hours for patients with febrile neutropenia and bacterial meningitis). The usual duration of treatment is 7-10 days; severe infections may require longer treatment.

Children weighing 40 kg or more should be prescribed Cefotrin as adults.

Administration of the drug. Cefotrin can be administered intravenously or by deep intramuscular injection into a large muscle mass (for example, into the upper outer quadrant of the gluteus maximus).

Intravenous administration. The intravenous route of administration is preferred for patients with severe or life-threatening infections.

For intravenous administration, Cefotrin should be dissolved in sterile water for injection, 5% glucose solution for injection, or 0.9% sodium chloride solution as indicated in the table below. Administer intravenously slowly over 3-5 minutes or via an intravenous infusion line.

Intramuscular administration. Cefothrin can be dissolved in sterile water for injection, 0.9% sodium chloride solution for injection, 5% glucose solution for injection, bacteriostatic water for injection with paraben or benzyl alcohol, 0.5% or 1% lidocaine hydrochloride solution in the concentrations indicated in the table below.

When using lidocaine as a solvent, a skin test should be performed before administration to check its tolerance.

As with other parenterally administered drugs, prepared drug solutions should be inspected for particulate matter prior to administration.

Appropriate microbiological studies should be performed to identify the causative organism(s) and determine susceptibility to cefepime. However, Cefotrin may be used as monotherapy before the causative organism is identified because it has a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms. In patients at risk of mixed aerobic-anaerobic (including Bacteroides fragilis) infections, treatment with Cefotrin in combination with an anaerobe-active agent may be initiated before the causative organism is identified.

Children

Use in children from 1 month of age.

Overdose

Symptoms: in cases 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 removal of cefepime from the body; peritoneal dialysis is ineffective. Severe immediate-type allergic reactions require the use of adrenaline and other forms of intensive therapy.

Adverse reactions

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

from the respiratory system: cough, sore throat, shortness of breath, breathing disorders;

Cardiovascular system: tachycardia, vasodilation;

from the digestive tract: nausea, vomiting, dyspepsia, oral candidiasis, change in taste, diarrhea, colitis (including pseudomembranous), abdominal pain, constipation;

from the nervous system: headache, insomnia, anxiety, convulsions, dizziness, paresthesias, epileptiform seizures;

from the hepatobiliary system: hepatitis, cholestatic jaundice;

Skin and subcutaneous tissue disorders: rash, itching, urticaria;

Reproductive system: genital itching, candidiasis;

others: asthenia, sweating, fever, vaginitis, erythema, chest pain, back pain, peripheral edema.

Local reactions at the site of drug administration:

with intravenous administration – phlebitis and inflammation;

with intramuscular injection – pain, inflammation.

Post-marketing studies:

encephalopathy (loss of consciousness, hallucinations, stupor, coma), epileptiform seizures, myoclonus, renal failure; anaphylaxis, including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia.

Laboratory parameters: increased levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, anemia, eosinophilia, increased prothrombin time or partial thromboplastin time (PTT) and positive Coombs test without hemolysis. Transient increases in blood urea nitrogen and/or serum creatinine and transient thrombocytopenia were observed in less than 0.5% of patients. Transient leukopenia and neutropenia were also observed.

Possible adverse reactions characteristic of cephalosporin antibiotics: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, toxic nephropathy, aplastic anemia, hemolytic anemia, bleeding, liver dysfunction, cholestasis, pancytopenia.

Expiration date

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

1 bottle of powder in a cardboard box.

Vacation category

According to the recipe.

Producer

Venus Remedies Limited.

Location of the manufacturer and its business address

Hill Top Industrial Estate, Jarmajari, ERIR Phase-1 (Ext.), Batoli Kalan, Baddi, Dist. Solan, Himachal Pradesh, 173205, India.