Cefepime powder solution 1g vials, 1pc

Composition

For 1 bottle: Active ingredient: Cefepimee hydrochloride monohydrate-1.1891 g, (in terms of Cefepimee) – 1.0 g, Auxiliary substance: L-arginine – 0.725 g

Pharmacological action

Pharmacotherapeutic group:

antibiotic-cephalosporin

ATX code:

J01DE01

Pharmacological properties

Pharmacodynamica Cefepime is a broad-spectrum cephalosporin antibiotic. Cefepimee inhibits the synthesis of bacterial cell wall proteins and has a broad spectrum of bactericidal action against various gram-positive and gram-negative bacteria, including most strains resistant to aminoglycosides or third-generation cephalosporin antibiotics, such as ceftazidime. Cefepimee is highly resistant to hydrolysis by most beta-lactamases, it has a low affinity for beta-lactamases and quickly penetrates into the cells of gram-negative bacteria. Cefepimee has been shown to have a very high affinity for penicillin-binding protein (PSB) type 3, a high affinity for PSB type 2, and a moderate affinity for PSB types 1a and 1b. Cefepimee has a bactericidal effect against a wide range of bacteria. Cefepimee is active against the following microorganisms:

Gram-positive aerobes: Staphylococcus aureus (including beta-lactamase-producing strains);Staphylococcus epidermidis (including beta – lactamase-producing strains);other strains of Staphylococcus spp., including Staphylococcus hominis, Staphylococcus saprophyticus;Streptococcus pyogenes (Group A streptococci);Streptococcus agalactiae (Group B streptococci);Streptococcus pneumoniae (including strains with moderate penicillin resistance-minimum inhibitory concentration from 0.1 to 1 mcg/ml);other beta-hemolytic Streptococcus spp. (groups C, G, F), Streptococcus bovis (group D), Streptococcus spp. of the viridans group. Note: Most strains of enterococci, such as Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to most cephalosporin antibiotics, including Cefepimee.

Gram-negative aerobes: Acinetobacter calcoaceticus (sub-strains anitratus, Iwoffii);Aeromonas hydrophila;Capnocytophaga spp. ;Citrobacter spp., including Citrobacter diversus, Citrobacter freundii, Campylobacter jejuni;Enterobacter spp., including Enterobacter cloacae, Enterobacter aerogenes, Enterobacter sakazakii;Escherichia coli;Gardnerella vaginalis;Haemophilus ducreyi;Haemophilus influenzae (including beta-lactamase producing strains);Haemophilus parainfluenzae;Hafnia alvei;Klebsiella spp., including Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella ozaenae;Legionella spp. ;Morganella morganii;Moraxella catarrhalis (Branhamella catarrhalis) (including beta-lactamase producing strains);Neisseria gonorrhoeae (including beta-lactamase producing strains);Neisseria meningitidis;Pantoea agglomerans (formerly known as Enterobacter agglomerans);Proteus spp., including Proteus mirabilis, Proteus vulgaris;Providencia spp., including Providencia rettgeri, Providencia stuartii;Pseudomonas spp., including Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas stutzeri, Salmonella spp. ;Serratia, including Serratia marcescens, Serratia liquefaciens;Shigella spp. ;Yersinia enterocolitica. Note: Cefepimee is inactive against many strains of Stenotrophomonas maltophilia, formerly known as Xanthomonas maltophilia and Pseudomonas maltophilia).

Anaerobes: Bacteroides spp. ;Clostridium perfringens;Fusobacterium spp. ;Mobiluncus spp. ;Peptostreptococcus spp. ;Prevotella melaninogenica (known as Bacteroides melaninogenicus);Veillonella spp. Note: Cefepimee is inactive against Bacteroides fragilis and Clostridium difficile.

Pharmacokinetics The average plasma concentrations of Cefepimee in adult healthy men at various times after a single intravenous use for 30 minutes to 12 hours and the maximum concentration (Cmax) are shown in the table below.

Mean plasma concentrations of Cefepimee (mcg/ml) after intravenous use

After intramuscular use, Cefepimee is completely absorbed.

Cmax and time to reach maximum concentration (Tmax) after a single intramuscular injection are shown in the table below.

Mean plasma concentrations of Cefepimee (mcg/ml) after intramuscular use

Therapeutic concentrations of Cefepimee are found in the following fluids and tissues: urine, bile, peritoneal, bullous fluid, bronchial mucosa, sputum, prostate, appendix, and gallbladder. The binding of Cefepimee to serum proteins is on average 16.4% and does not depend on the concentration of the drug in the blood serum.

Cefepimee is metabolized to N-methylpyrrolidine, which is rapidly converted to N-methylpyrrolidine oxide.

Cefepimee is mainly excreted by the kidneys, by glomerular filtration (renal clearance averages 110 ml / min). The urine contains approximately 85% of the administered dose of unchanged Cefepimee, less than 1% of N-methylpyrrolidine, about 6.8% of N-methylpyrrolidine oxide, and about 2.5% of the Cefepimee epimer.

After use of doses from 250 mg to 2 g, the half-life of Cefepimee from the body is on average about 2 hours. The total clearance is on average 120 ml / min. When the drug was administered intravenously to healthy volunteers at a dose of 2 g every 8 hours for 9 days, no accumulation of the drug was observed.

Patients with impaired renal Functionthe elimination half-life in renal failure increases, and there is a linear relationship between total clearance and creatinine clearance. In severe renal impairment requiring dialysis, the average elimination half-life is 13 hours on hemodialysis and 19 hours on continuous peritoneal dialysis. In case of impaired renal function, dose adjustment is required.

Patients with impaired liver function The pharmacokinetics of Cefepimee do not change in patients with impaired liver function. No dose adjustment is required for these patients.

Patients over 65 years of age After a single intravenous use of 1 g of the drug to healthy volunteers over 65 years of age, there was an increase in the area under the concentration-time curve (AUC) and a decrease in renal clearance compared to young volunteers. In older patients with impaired renal function, dose adjustment is required.

Detipharmacokinetics of the drug was studied in children aged 2 months to 11 years after a single dose of 50 mg/kg body weight intravenously or intramuscularly, as well as after repeated use of the drug (every 8-12 hours, for at least 48 hours). After a single intravenous injection, the total clearance and volume of distribution were 3.3 ml / min / kg and 0.3 l/kg, respectively. The elimination half-life averaged 1.7 hours. Renal elimination of Cefepimee unchanged was 60.4% of the administered dose, and renal clearance averaged 2.0 ml / min / kg.

After repeated intravenous use, the steady-state plasma concentration of Cefepimee, as well as other pharmacokinetic parameters, did not differ from those after a single use. Age and gender of patients did not significantly affect the total clearance and volume of distribution adjusted for body weight. After intramuscular use, the maximum concentration of Cefepimee in the blood plasma at steady state averaged 68 mcg / ml and was reached on average in 0.75 hours. 8 hours after intramuscular use, the plasma concentrations of Cefepimee averaged 6 micrograms / ml. The absolute bioavailability of Cefepimee after intramuscular injection averaged 82%.

Concentrations of the drug in the cerebrospinal fluid (CSF) and in blood plasma in children with bacterial meningitis

* * age of patients: 3.1 months-12 years, mean age: 3 years. The dose of the drug is 50 mg/kg of body weight when administered intravenously for 5 to 20 minutes every 8 hours. Plasma and CSF concentrations were determined at the end of use on day 2 or 3 of treatment with the drug.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to Cefepimee in adults:

– Lower respiratory tract infections, including pneumonia and bronchitis; – Urinary tract infections, both complicated, including pyelonephritis, and uncomplicated; – Skin and soft tissue infections;- Abdominal infections, including peritonitis and biliary tract infections;- Gynecological infections; – Septicemia; – Febrile neutropenia.

Prevention of possible infections during oral surgery.

Infectious and inflammatory diseases caused by microorganisms sensitive to Cefepimee in children:

– Pneumonia; – Urinary tract infections, both complicated, including pyelonephritis, and uncomplicated; – Skin and soft tissue infections;- Septicemia; – Febrile neutropenia;- Bacterial meningitis.

Use during pregnancy and lactation

No adequate and controlled clinical trials have been conducted in pregnant women. During pregnancy, the drug should only be used if the intended benefit to the mother exceeds the potential risk to the fetus.

Cefepimee is found in breast milk in very low concentrations.

During breastfeeding, the drug should only be used if the intended benefit to the mother exceeds the potential risk to the child.

Contraindications

Hypersensitivity to Cefepimee or L-arginine, as well as to cephalosporin antibiotics, penicillins or other beta-lactam antibiotics.

Children under 2 months of age.

With caution

, a history of gastrointestinal diseases (especially colitis), renal failure (creatinine clearance less than 60 ml/min).

Side effects

The most common side effects are from the gastrointestinal tract and allergic reactions. Side effects by organ and system are listed below according to their frequency: very common (≥10%); common (≥1% and <10%); uncommon (≥0.1% and <1%); rare (≥0.01% and < 1%).

Allergic reactionscastly – skin rashes; Infrequently-erythema, urticaria, pruritus; Rarely-anaphylactic reactions; Frequency unknown – anaphylactic shock, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, angioedema.

Infectioninecastly-candidiasis of the oral mucosa, vaginal infections; Rarely-candidiasis.

From the central nervous system: Often-headache; Rarely-convulsions, paresthesia, dysgesia, dizziness; Frequency unknown (post-marketing experience): encephalopathy (impaired consciousness, including confusion, hallucinations, stupor and coma), myoclonus, convulsions and non-convulsive epileptic status.

Although most cases were reported in patients with renal insufficiency who received Cefepimee at doses higher than recommended, in some cases neurotoxicity was observed in patients who underwent dose adjustment depending on the degree of renal insufficiency.

From the urinary system, the frequency is unknown – renal failure, toxic nephropathy.

From the digestive system: Often – diarrhea; Infrequently-nausea, vomiting, colitis (including pseudomembranous colitis); Rarely-abdominal pain, constipation; Frequency unknown-digestive disorders.

From the respiratory system Occasionally-shortness of breath.

From the cardiovascular system, rarely-vasodilation; Frequency unknown-bleeding.

General reactions and reactions at the injection site Often – phlebitis at the injection site, pain at the injection site; Infrequently – fever and inflammation at the injection site; Rarely-chills.

Laboratory parameters Often – increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase (ALP), total bilirubin, anemia, eosinophilia, increased prothrombin time or partial thromboplastin time;Infrequently – increased blood urea nitrogen, serum creatinine, thrombocytopenia, leukopenia and neutropenia;Frequency unknown – aplastic anemia, hemolytic anemia, agranulocytosis.

Other symptoms include genital pruritus, taste changes, vaginitis, erythema, false positive Coombs test without hemolysis.

Interaction

The solution of the drug is pharmacologically incompatible with solutions of metronidazole, vancomycin, gentamicin, tobramycin sulfate, netilmycin sulfate, so they should not be mixed. However, with simultaneous use of Cefepimee and the above drugs, each of them can be administered separately.

Data on the compatibility of Cefepimee solutions and other medicinal products, as well as their stability, are given in the table below.

Co-use with bacteriostatic antibiotics may reduce the effectiveness of beta-lactam antibiotics.

How to take, course of use and dosage

of Cefepimee can be administered intravenously (iv) or intramuscularly (iv). The dose and route of use depend on the sensitivity of the pathogens, the severity of the infection, the state of renal function and the general condition of the patient. The intravenous route of use is recommended for patients with severe or life-threatening infections, especially if septic shock is at risk. Intramuscular dose up to 1 g (volume The maximum dose (2 g/6.2 ml) should be given as two injections at different locations.

For children, the dose should not exceed the maximum recommended dose for adults (2 g IV every 8 hours). Experience with intramuscular use of Cefepimee to children is limited.

Adults and children with a body weight of more than 40 kg with normal kidney function

The usual duration of treatment is 7-10 days; severe infections may require longer treatment.

In the case of treatment of febrile neutropenia, the usual duration of treatment is 7 days or until neutropenia disappears.

Prevention of possible infections during surgical surgeries60 minutes before the start of surgery,2 g of the drug is administered intravenously as an infusion for 30 minutes. Immediately after the end of the infusion,500 mg of metronidazole is administered intravenously. Due to the incompatibility of metronidazole and Cefepimee, they should not be administered simultaneously or mixed. The infusion system should be flushed before use of metronidazole (see “Intravenous use”). The metronidazole solution should be prepared in accordance with the instructions for use of metronidazole. During long-term (more than 12 hours) surgical operations,12 hours after the first dose, it is recommended to re-administer Cefepimee in the same dose, followed by the introduction of metronidazole.

Children from 2 months of age with a body weight of up to 40 kg, the usual recommended dose for urinary tract infections, skin and soft tissue infections, and pneumonia is 50 mg / kg every 12 hours for 10 days. In case of severe infections-every 8 hours. Patients with febrile neutropenia, septicemia, bacterial meningitis should be given 50 mg / kg every 8 hours for 7-10 days.

Patients with impaired renal function

Patients with impaired renal function need to adjust the dosage of Cefepimee to compensate for the reduced rate of excretion of the drug in the urine. The dosage regimen should be prescribed depending on the degree of renal failure, the severity of infection and the sensitivity of microorganisms. In patients with mild to moderate renal impairment, the initial dose of the drug should be the same as in patients with normal renal function.

Recommended maintenance doses of Cefepimee are shown in the table. Creatinine clearance for men can be calculated based on the concentration of serum creatinine using the following formula:

Creatinine clearance for women can be calculated by multiplying the obtained value by 0.85.

* For patients on hemodialysis, it is recommended to reduce the dose of Cefepimee: 1 g on the first day of treatment and then 0.5 g per day for all infections, with the exception of febrile neutropenia, where the dose is 1 g per day. On dialysis days, Cefepimee should be administered at the end of dialysis. If possible, the drug should be administered at the same time every day.

During hemodialysis, approximately 68% of the administered dose of the drug is removed from the body in 3 hours.

With continuous outpatient peritoneal dialysis, the drug can be used in the initial recommended doses of 0.5 g,1 g or 2 g, depending on the severity of the infection, with an interval of 48 hours between use.

Children with impaired renal function For children with impaired renal function, it is recommended to reduce the dose or increase the interval between injections, as indicated in the table above. Creatinine clearance is calculated using the following formulas:

Patients with hepatic impairment No dose adjustment is required for patients with hepatic impairment.

Intravenous use is recommended for patients with severe or life-threatening infections, especially if septic shock is at risk.

Preparation of the solution for intravenous use The drug is dissolved in 5,10 or 20 ml of sterile water for injection,5% dextrose solution and 0.9% sodium chloride solution for injection, as indicated in the table below, and is administered for 3-5 minutes either directly into a vein or into an intravenous system through which a compatible solution for intravenous use enters the patient’s body.

Preparation of the solution for intravenous infusionthe prepared solution (see above) is transferred to an infusion vessel with other compatible solutions for intravenous infusions (see below) and administered for at least 30 minutes.

Solutions of the drug with a concentration of 1-40 mg / ml are compatible with the following parenteral solutions:; 5% dextrose solution and 0.9% sodium chloride solution for injection;, Ringer’s lactate solution.

Intramuscular use: dose up to 1 g (volume The maximum dose (2 g/6.2 ml) should be given as two injections at different locations.

Preparation of the solution for intramuscular injectionthe drug is dissolved in sterile water for injection,5% dextrose solution or 0.9% sodium chloride solution for injection, bacteriostatic water for injection with parabens or benzyl alcohol,0.5% or 1% lidocaine solution, as indicated in the table below.

Storage of solutions for intravenous and intramuscular use

Prepared solutions of the drug for intramuscular and intravenous use are stable for 24 hours at room temperature or 7 days when stored in the refrigerator (2-8°C).

Like all solutions for parenteral use, the prepared solutions of the drug should be checked for the absence of visible mechanical inclusions before use. Otherwise, it is forbidden to use the prepared solution.

During storage, the powder and the prepared solution may darken, which does not affect the activity and quality of the drug.

Overdose

Symptoms: encephalopathy (confusion, hallucinations, stupor, coma), myoclonic seizures, increased neuromuscular excitability. Treatment: symptomatic and supportive care. If the recommended dose is significantly exceeded, especially in patients with impaired renal function, hemodialysis is indicated.

Special instructions

In the presence of factors that may cause impaired renal function, it is necessary to adjust the dose of Cefepimee to compensate for the reduced rate of excretion of the drug in the urine. The dosage regimen depends on the degree of renal failure, the severity of infection and the sensitivity of microorganisms. For mild or moderate renal impairment, the initial dose of the drug is the same as for normal renal function. The risk of toxic reactions is particularly increased in elderly patients with impaired renal function.

The following serious adverse reactions, including life-threatening or fatal ones, were reported during post-marketing surveillance: encephalopathy (impaired consciousness, including confusion, hallucinations, stupor and coma), myoclonus, convulsions and status non-convulsive epileptic status.

Most cases were reported in patients with renal insufficiency who did not undergo dose adjustment. However, in some cases, neurotoxicity was observed in patients who underwent dose adjustment depending on the degree of renal insufficiency. In most cases, the symptoms of neurotoxicity were reversible and disappeared after discontinuation of the drug and / or after hemodialysis. If neurotoxicity is associated with the use of Cefepimee, discontinuation of Cefepimee therapy or dose adjustment should be considered in patients with renal insufficiency. Before starting treatment, it is necessary to establish whether the patient has a history of allergic reactions to Cefepimee, other cephalosporin antibiotics, penicillins and other beta-lactam antibiotics, as well as other forms of allergies. Severe hypersensitivity reactions, sometimes fatal, have been reported with all types of beta-lactam antibiotics.

Cephalosporin antibiotics can cause a false positive reaction to glucose in the urine in tests based on the reduction of copper ions (with Benedict or Fehling solutions or with Clinitest tablets), but not in enzyme tests (with glucose oxidase). In this regard, it is recommended to use enzyme tests with glucose oxidase to determine glucose in the urine.

If an allergic reaction develops, you should stop treatment with the drug and take appropriate measures. If a severe allergic reaction develops (for example, an anaphylactic reaction), epinephrine and other maintenance therapy may be required immediately during the use of the drug.

When prescribing empirical treatment, it is necessary to take into account data on the acquired resistance of pathogenic microorganisms.

Microbial resistance can change over time and geographical location. Appropriate tests should be performed to identify the pathogen and determine sensitivity to Cefepimee. Cefepimee can be used as monotherapy even before the identification of the pathogen, as it has a wide spectrum of antibacterial action against gram-positive and gram-negative microorganisms. If there is a risk of mixed aerobic / anaerobic infection (especially when microorganisms that are not sensitive to Cefepimee may be present), treatment with Cefepimee in combination with a drug acting on anaerobes can be started before the pathogen is identified.

After identifying the pathogen and determining sensitivity to antibiotics, treatment should be carried out in accordance with the test results.

As with other antibiotics, treatment with Cefepimee can lead to colonization of insensitive microflora. If superinfections develop during treatment, appropriate measures should be taken.

No effect on fertility was observed in rat studies. There are no data on the effect of Cefepimee on human fertility.

Clostridium difficile-associated diarrhea When almost all broad-spectrum antibiotics are used, Clostridium difficile – associated diarrhea (CDAD-Clostridium difficile-associated diarrhea) can occur, which can occur in both mild and severe forms, up to a fatal outcome.

If diarrhea occurs during treatment with the drug, it is necessary to confirm the diagnosis of CDAD. The patient should be carefully monitored for the development of CDAD, as cases of its occurrence have been reported more than two months after discontinuation of antibiotics. If CDAD is suspected or confirmed, the use of antibiotics other than those prescribed for the suppression of Clostridium difficile should be discontinued. Do not use medications that inhibit intestinal motility.

Influence on the ability to drive vehicles and mechanisms

The effect of the drug on the ability to concentrate attention has not been studied, however, given the possibility of developing side effects from the central nervous system, during treatment with the drug, you should refrain from driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

In a dark place at a temperature not exceeding 30°C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Cefepimee

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion