Cefepime-Alkem - instructions for use, dose, side effects, contraindications

Antibacterial agent from the group of cephalosporins of the IV generation. It acts bactericidal, disrupting the synthesis of the cell wall of microorganisms. Has a wide spectrum of action against Gram-positive and Gram-negative bacteria, resistant to aminoglycosides and / or cephalosporin antibiotics of the third generation. Highly resistant to hydrolysis by most beta-lactamases and rapidly penetrates into gram-negative bacterial cells.Inside the bacterial cell, the molecular target is penicillin-binding proteins.

Active in vivo and in vitro for the following microorganisms:

Gram-positive aerobes: Staphylococcus aureus (only methicillin-sensitive strains); Streptococcus pneumoniae; Streptococcus pyogenes (Group A); Streptococcus spp. groups viridans.

Gram-negative aerobes: Enterobacter spp.; Escherichia coli; Klebsiella pneumoniae; Proteus mirabilis; Pseudomonas aeruginosa.

In vitro active (but not clinically significant) for Gram-positive aerobes: Staphylococcus epidermidis (only methicillin-sensitive strains); Staphylococcus saprophyticus\ Streptococcus agalactiae (group B); Gram-negative aerobes: Acinetobacter lwoffii; Citrobacter diversus; Citrobacter freundii; Enterobacter agglomerans\ Haemophilus influenzae (including strains producing beta-lactamase); Hafnia alvei; Klebsiella oxytoca; Moraxella catarrhalis (including strains producing beta-lactamases); Morganella morganii; Proteus vulgaris; Providencia rettgeri; Providencia stuartii; Serratia marcescens. Most strains Enterococcus, including Enterococcus faecalis, Staphylococcus spp. (methicillin-resistant staphylococci), Stenotrophomonas (formerly known as Xanthomonas maltophilia and Pseudomonas maltophilia), Clostridium difficile are not sensitive to cefepime.

Pharmacokinetics:

- Suction and distribution: Bioavailability of 100%. The maximum concentration in the blood plasma (Cmax) at intramuscular injection in doses of 0.5 g, 1 g and 2 g - 14, 30 and 57 μg / ml, respectively; when administered intravenously at doses of 0.25 g, 0.5 g, 1 g and 2 g - 18, 39, 82 and 164 μg / ml, respectively.Time to reach the average therapeutic concentration in blood plasma - 12 hours; the average therapeutic concentration for intramuscular injection is 0.2 μg / ml, with intravenous - 0.7 μg / ml. High concentrations are determined in urine, bile, peritoneal fluid, blister exudate, bronchial mucus secretion, sputum, prostate gland, appendix and gallbladder. Volume of distribution

- 0,25 l / kg, in children from 2 months to 16 years - 0,33 l / kg. Connection with blood plasma proteins - 20%.

- Metabolism: Metabolized in the liver and kidneys by 15%.

- Breeding: The half-life (T1 / 2) is 2 hours, the total clearance is 120 ml / min, the renal clearance is 110 ml / min. It is excreted by the kidneys (by glomerular filtration in unchanged form - 85%), with breast milk. The half-life (T1 / 2) for hemodialysis is 13 hours, with continuous peritoneal dialysis - 19 hours.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to cefepime:

- Infections of the lower respiratory tract, including pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including cases of association with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp.;

- Urinary tract infections, both complicated, for example, pyelonephritis, and uncomplicated, caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis;

- Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (only methicillin-sensitive strains), Streptococcus pyogenes;

- Complicated intra-abdominal infections (in combination with metronidazole), including peritonitis and bile duct infections caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp.;

- Febrile neutropenia (empirical treatment in the form of monotherapy).

Contraindications:Hypersensitivity to cefepime or arginine (including other cephalosporins, penicillins, and other beta-lactam antibiotics), children under 2 months (for intravenous administration); Children under 12 years of age (for intramuscular injection).

Carefully:Pregnancy, lactation, diseases of the gastrointestinal tract (including in the anamnesis), especially colitis; severe chronic renal failure.

Pregnancy and lactation:Use in pregnancy is possible only if the intended benefit to the mother exceeds the risk to the fetus. Preclinical trials demonstrated no effect on reproductive function and any adverse effects on the fetus.However, adequate and strictly controlled studies in pregnant women have not been conducted, so the drug should be used during pregnancy only under the supervision of a doctor.

Cefepime is excreted in breast milk at very low concentrations, and its use is possible if the perceived benefit to the mother exceeds the risk to the child.

Dosing and Administration:

The drug is administered intravenously in the form of infusion (for at least 30 minutes) or intramuscularly (only with complicated or uncomplicated urinary tract infections of mild and moderate severity caused by Escherichia coli).

The dose and route of administration depend on the sensitivity of the microorganisms of the pathogens, the severity of the infection, the state of kidney function in the patient and the general condition of the patient.

- Pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including cases of association with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp.: intravenously 1-2 g every 12 hours for 10 days.

- Febrile neutropenia (empirical therapy): intravenously 2 g every 8 hours for 7 days or until neutropenia is resolved.

- Complicated or uncomplicated urinary tract infections of mild and moderate severity caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis: intravenously or intramuscularly (only for infections caused by Escherichia coli) for 0.5-1 g every 12 hours for 7-10 days.

- Severe complicated or uncomplicated urinary tract infections (including pyelonephritis) caused by Escherichia coli or Klebsiella pneumoniae', intravenously 2 g every 12 hours for 10 days.

- Severe and severe infections of the skin and soft tissues caused by Staphylococcus aureus (only methicillin-sensitive strains), Streptococcus pyogenes: intravenously 2 g every 12 hours for 10 days.

Complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp.: intravenously, 2 g every 12 hours for 7-10 days.

In children from 2 months to 16 years and with a body weight of up to 40 kg, the recommended dosing regimen for all indications (excluding febrile neutropenia) is 50 mg / kg every 12 hours intravenously; with febrile neutropenia - 50 mg / kg every 8 hours. Duration of treatment as in adults.

In chronic renal failure (CRF), the dose is given depending on the severity of the infection and the clearance of creatinine (CC): more than 60 ml / min - 0.5-1-2 g every 12 hours or 2 g every 8 hours, KK 30-60 ml / min - 0.5-1-2 g every 24 hours or 2 g every 12 hours, with KK 11-29 ml / min - 0.5-1-2 g every 24 hours, less than 11 ml / min - 0, 25-0.5-1 g every 24 hours; permanent ambulatory peritoneal dialysis - 0.5-1-2 g every 48 hours.Patients on hemodialysis receive 1 g on the 1st day, then 0.5 g every 24 hours for all infections and 1 g every 24 hours for the treatment of febrile neutropenia. On the day of hemodialysis, the drug is administered after the end of the hemodialysis session; it is desirable to enter cefepime every day at the same time. Data on the use of the drug in children with concomitant chronic renal failure are not available, however, given the similar pharmacokinetics in children and adults, the dosage regimen (dose reduction or increase in the interval between administrations) in children with CRF is similar to that for adults.

Preparation of a solution for intravenous administration

For intravenous administration, the drug is dissolved in 10 ml of water for injection, 5% solution of dextrose or 0.9% solution of sodium chloride, as indicated in the table below, and administered intravenously for 3-5 minutes. For intravenous infusion, the prepared solution is combined with other solutions for intravenous infusions (0.9% sodium chloride solution, 5% or 10% dextrose solution, Ringer's solution with lactate and 5% dextrose solution); the maximum concentration of 40 mg / ml and injected for at least 30 minutes.

Preparation of solution for intramuscular injection

The drug is dissolved in water for injection, 5% dextrose solution or 0.9% solution of sodium chloride, bacteriostatic water for injection with paraben or petrol alcohol, 0.5% or 1% lidocaine hydrochloride solution, as indicated in the table below.

Like other parenteral drugs, the prepared solutions of the drug before administration should be checked for the absence of mechanical inclusions.

Volume of dilution solution (ml)

The approximate volume of the solution obtained (ml)

Approximate

concentration of cefepime (mg / ml)

Intravenous administration:

1000 mg / bottle

10,0

11,3

100

Intramuscular administration:

1000 mg / bottle

2,4

3,6

280

Since the administration of the drug is generally painless, in most cases there is no need to use a lidocaine hydrochloride solution as a solvent.

Side effects:

The following undesirable phenomena noted with the use of the drug are distributed according to the frequency of occurrence in accordance with the following gradation: often (from > 1/100 to <1/10), infrequently (from > 1/1000 to <1/100), rarely (from > 1/10000 to <1/1000), very rarely (<1/10000).

AAllergic reactions: often - skin rash (including erythematous rashes); infrequently - hives, itching; frequency is unknown - anaphylactoid reactions, anaphylactic shock, eosinophilia, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

Local reactions: when administered intravenously often - phlebitis, pain and / or inflammation at the injection site, an intramuscular - redness and soreness at the injection site.

From the nervous system: infrequently - a headache; frequency neizvestna- drowsiness, neurotoxicity, encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, coma), myoclonus, seizures, status epilepticus small seizures, dizziness, insomnia, paresthesia, anxiety.

From the genitourinary system: infrequently - vaginitis; frequency is unknown - genital itching.

From the urinary system: frequency unknown - renal failure, impaired renal function, toxic nephropathy.

From the digestive system: often - diarrhea; infrequently - nausea, vomiting, pseudomembranous colitis,Candidiasis of the oral mucosa; frequency unknown - constipation, abdominal pain, indigestion, anorexia, stomatitis, diarrhea caused by Clostridium difficile.

From the hematopoiesis: infrequently - thrombocytopenia, leukopenia, neutropenia; frequency unknown - aplastic anemia, pancytopenia, hemolytic anemia, bleeding (including nasal), bleeding.

From the respiratory system: rarely shortness of breath; frequency is unknown - cough.

From the cardiovascular system: infrequently - tachycardia; frequency unknown - peripheral edema.

Laboratory indicators: very often - a false positive test of Coombs; often - an increase in APTT (activated partial thromboplastin time), increased activity ALT (alanine aminotransferase), increased activity ACT

(aspartate aminotransferase), hypophosphatemia; infrequently hyperkreatininemia, increased urea concentration, decreased hematocrit, increased alkaline phosphatase (AC) activity, hypocalcemia, hyperphosphataemia, hyperkalemia, increased urea concentration, hypercalcemia, hyperbilirubinemia; frequency unknown - hypokalemia, hypomagnesemia, increased prothrombin time.

Other: infrequently - fever, sore throat, thoracology, increased sweating, back pain, asthenia, development of superinfection; frequency unknown - impaired liver function (including cholestasis), chest pain, change in taste.

Overdose:

Symptoms: convulsions, encephalopathy, neuromuscular excitation (often occur in patients with CRF).

Treatment: hemodialysis and symptomatic therapy.

Interaction:

Cefepime is pharmaceutically incompatible with other antimicrobial drugs and heparin.

Diuretics, aminoglycosides, polymyxin B reduce the tubular secretion of cefepime and increase its concentration in the blood plasma, extend T1 / 2, increase nephrotoxicity (increases the risk of developing nephronecrosis). Cefepim increases the ototoxicity of aminoglycosides.

Nonsteroidal anti-inflammatory drugs, slowing the excretion of cephalosporins, increase the risk of bleeding. When used simultaneously with bactericidal antibiotics (aminoglycosides), synergism is manifested, with bacteriostatic (macrolides, chloramphenicol, tetracyclines) - antagonism.

Incompatible with a solution of metronidazole (before the introduction of a solution of metronidazole for prophylaxisinfections during surgical interventions should be flushed with the infusion system from the cefepime solution). To avoid possible drug interactions with other drugs, cefepime solutions (like most other beta-lactam antibiotics) should not be administered concomitantly with solutions of vancomycin, gentamicin, tobramycin, netilmicin. When prescribing cefepime with the listed drugs, each antibiotic should be administered separately.

Special instructions:

If pseudomembranous colitis occurs with prolonged diarrhea, stop taking and prescribe vancomycin (inside) or metronidazole. There is a possibility of cross-over hypersensitivity in patients with allergic reactions to penicillins.

When combined severe renal and hepatic insufficiency should regularly determine the concentration of the drug in the blood plasma (dose adjustment is performed depending on the creatinine clearance). With prolonged treatment, regular monitoring of peripheral blood, indicators of the functional state of the liver and kidneys is necessary. With a mixed aerobic-anaerobic infection before identifying pathogens, a combination with drugs active against anaerobes is appropriate.

Patients who have a meningeal dissemination from a distant foci of infection, suspicions of meningitis or a diagnosis of meningitis have been confirmed, an alternative antibiotic with confirmed clinical efficacy should be prescribed. It is possible to detect a false positive sample of Coombs, a false positive test for glucose in the urine.

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

Form release / dosage:

Powder for the preparation of solution for intravenous and intramuscular administration of 1000 mg.

Packaging:

By 1000 mg of active ingredient in a colorless glass bottle of 15 ml, sealed with butyl cork of gray color and closed with an aluminum cap with a tear-off orange lid of the "flip-off" type. 1 bottle with instructions for use in a cardboard pack.

For hospitals:

For 50 bottles 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 25 ° C. The prepared solution is stable for 24 hours at room temperature (not higher than 25 ° C) or 7 days when stored in a refrigerator (2-8 ° C). Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002342

Date of registration:13.01.2014

Date of cancellation:2019-01-13

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

Manufacturer: & nbsp

ALKEM LABORATORIES, Ltd. India

Representation: & nbspPharmaReg Ltd.PharmaReg Ltd.Russia

Information update date: & nbsp20.10.2015

Illustrated instructions

Instructions

Cefepim-Alkem (Cefepime-Alkem)