Cefurus, 1.5 g

Pharmacodynamics

Mechanism of action

Cefuroxime is active against a wide range of pathogens, including strains producing betalactamases. ‑

Cefuroxime has good resistance to bacterial betalactamases ‑and, accordingly, is active against a wide range of ampicillin ‑and amoxicillin-resistant ‑strains.

The bactericidal effect of cefuroxime is associated with suppression of bacterial cell wall synthesis as a result of binding to the main target proteins‑. ‑

Pharmacodynamic effects

Cefuroxime is a bactericidal antibiotic of cephalosporin group, resistant to the action of most betalactamases ‑and active against a wide range of Gram-positive and Gram-negative microorganisms. The prevalence of acquired bacterial resistance to cefuroxime varies regionally and over time, and resistance can be very high in certain types of microorganisms. It is preferable to have local sensitivity data, especially for therapy of severe infections.

Cefuroxime is generally active in vitro against the following microorganisms.

Bacteria generally sensitive to cefuroxime

Gram-positive aerobes:

– Staphylococcus aureus (strains sensitive to methicillin)1;

– ‑coagulazonegative staphylococci (methicillin-sensitive strains);

– Streptococcus pyogenes1;

– betahemolytic ‑streptococci.

– Gram-negative aerobes:

– Haemophilus influenzae1, including ampicillin-resistant strains;

– Haemophilus parainfluenzae1;

– Moraxella catarrhalis1;

p> – Neisseria gonorrhoeae1, including penicillinase-producing and non-penicillinase-producing strains;

– Neisseria meningitidis;

– Shigella spp.

Gram-positive anaerobes:

– Peptostreptococcus spp.;

– Propionibacterium spp.

Spirochetes:

Borrelia burgdorferi1.

Bacteria for which acquired resistance to cefuroxime is likely

Gram-positive aerobes:

– Streptococcus pneumoniae1;

– Streptococcus viridians.

Gram-negative aerobes:

– Bordetella pertussis;

– Citrobacter spp. except C. freundii;

– Enterobacter spp, except E. aerogenes and E. cloacae;

– Escherichia coli1;

– Klebsiella spp, including K. pneumonia1;

– Proteus mirabilis;

– Proteus spp. except P. penneri and P. vulgaris Providencia spp.

Gram-positive anaerobes:

– Clostridium spp. except C. difficile.

Gram-negative anaerobes:

– Bacteroides spp. except B. fragilis;

– Fusobacterium spp.

Bacteria naturally resistant to cefuroxime

Gram-positive aerobes:

– Enterococcus spp. including E. faecalis and E. faecium;

– Listeria monocytogenes.

Gram-negative aerobes:

– Acinetobacter spp.;

– Burkholderia cepacia;

– Campylobacter spp.

– Citrobacter freundii;

– Enterobacter aerogenes;

– Enterobacter cloacae;

– Morganella morganii;

– Proteus penneri;

– Proteus vulgaris;

– Pseudomonas spp., including P. aeruginosa;

– Serratia spp.;

– Stenotrophomonas maltophilia.

Gram-positive anaerobes:

– Clostridium difficile.

Gram-negative anaerobes:

– Bacteroides fragilis.

Other:

– Chlamydia spp.;

– Mycoplasma spp.

1 For these bacteria, the clinical efficacy of cefuroxime has been demonstrated in clinical trials.

Pharmacokinetics

Absorption

The maximum concentration of cefuroxime in blood plasma after intramuscular administration is observed within 30 to 45 minutes.

Distribution

The drug is 33-50% bound to plasma proteins (depending on the technique used).

Concentrations of cefuroxime that exceed the minimum suppressive concentration for most microorganisms can be achieved in bone tissue, synovial and intraocular fluid. Cefuroxime penetrates the blood-brain barrier in inflammation of the brain membranes.

Metabolism

Cefuroxime is not metabolized and is excreted by glomerular filtration and tubular secretion.

Elimation

The elimination half-life of cefuroxime from serum after intramuscular or intravenous administration is approximately 70 minutes. In newborn children the half-life of cefuroxime may be 3-5 times longer than in adults.

The concomitant administration of probenecid prolongs cefuroxime excretion, which leads to increased maximum serum cefuroxime concentration.

Within 24 hours after parenteral administration, cefuroxime is almost completely (85-90%) excreted unchanged through the kidneys, with most of the drug in the first 6 hours.

The serum concentrations of cefuroxime are reduced with dialysis.

Indications

Bacterial infections caused by bacteria sensitive to cefuroxime, as well as in cases where the pathogen has not yet been identified:

– lower respiratory tract infections, for example, bacterial pneumonia, acute bacterial bronchitis and exacerbation of chronic bronchitis, infected bronchiectasis, lung abscess, postoperative infectious diseases of the chest organs;

– infections of the ENT organs, for example, otitis media, sinusitis, tonsillitis, pharyngitis;

– urinary tract infections, for example, acute and chronic pyelonephritis, cystitis, asymptomatic bacteriuria;

– gonorrhea;

– infections of the skin and soft tissues, such as cellulitis, erysipelas and wound infections;

– infections of bones and joints, such as osteomyelitis and septic arthritis;

– obstetric and gynecological infections, as well as inflammatory diseases of the pelvic organs;

– other infections, including septicemia, bacterial meningitis, intra-abdominal infections, such as peritonitis;

– prevention of infectious complications during operations on the abdominal organs, pelvis, orthopedic operations, operations on the heart, lungs, esophagus and blood vessels – where there is an increased risk of infectious complications.

The sensitivity of bacteria to cefuroxime varies regionally and over time. Where possible, local sensitivity data should be taken into account (see subsection “Pharmacodynamics”).

If necessary, cefuroxime can be used for step-down therapy with a transition to oral cefuroxime axetil, mainly for the treatment of pneumonia and exacerbations of chronic bronchitis.

Pharmacological effect

Pharmacodynamics

Mechanism of action

Cefuroxime is active against a wide range of pathogens, including strains that produce beta-lactamases.

Cefuroxime has good resistance to bacterial beta-lactamases and, accordingly, is active against a wide range of ampicillin- and amoxicillin-resistant strains.

The bactericidal effect of cefuroxime is associated with the suppression of bacterial cell wall synthesis as a result of binding to the main target proteins.

Pharmacodynamic effects

Cefuroxime is a bactericidal antibiotic of the cephalosporin group, resistant to most beta-lactamases and active against a wide range of gram-positive and gram-negative microorganisms. The prevalence of acquired bacterial resistance to cefuroxime varies by region and over time, and resistance can be very high in certain types of microorganisms. It is preferable to have local susceptibility data, especially when treating severe infections.

Cefuroxime is generally active in vitro against the following microorganisms.

Bacteria usually sensitive to cefuroxime

Gram-positive aerobes:

– Staphylococcus aureus (strains sensitive to methicillin)1;

– coagulase-negative staphylococci (strains sensitive to methicillin);

– Streptococcus pyogenes1;

– beta-hemolytic streptococci.

Gram-negative aerobes:

– Haemophilus influenzae1, including ampicillin-resistant strains;

– Haemophilus parainfluenzae1;

– Moraxella catarrhalis1;

– Neisseria gonorrhoeae1, including strains that produce and do not produce penicillinase;

– Neisseria meningitidis;

– Shigella spp.

Gram-positive anaerobes:

– Peptostreptococcus spp.;

– Propionibacterium spp.

Spirochetes:

Borrelia burgdorferi1.

Bacteria for which acquired resistance to cefuroxime is likely

Gram-positive aerobes:

– Streptococcus pneumoniae1;

– streptococci of the Viridians group.

Gram-negative aerobes:

– Bordetella pertussis;

– Citrobacter spp., except C. freundii;

– Enterobacter spp., except E. aerogenes and E. cloacae;

– Escherichia coli1;

– Klebsiella spp., including K. pneumonia1;

– Proteus mirabilis;

– Proteus spp., except P. penneri and P. vulgaris Providencia spp.;

– Salmonella spp.

Gram-positive anaerobes:

– Clostridium spp., except C. difficile.

Gram-negative anaerobes:

– Bacteroides spp., except B. fragilis;

– Fusobacterium spp.

Bacteria that are naturally resistant to cefuroxime

Gram-positive aerobes:

– Enterococcus spp., including E. faecalis and E. faecium;

– Listeria monocytogenes.

Gram-negative aerobes:

– Acinetobacter spp.;

– Burkholderia cepacia;

– Campylobacter spp.;

– Citrobacter freundii;

– Enterobacter aerogenes;

– Enterobacter cloacae;

– Morganella morganii;

– Proteus penneri;

– Proteus vulgaris;

– Pseudomonas spp., including P. aeruginosa;

– Serratia spp.;

– Stenotrophomonas maltophilia.

Gram-positive anaerobes:

– Clostridium difficile.

Gram-negative anaerobes:

– Bacteroides fragilis.

Other:

– Chlamydia spp.;

– Mycoplasma spp.;

– Legionella spp.

1 For these bacteria, the clinical effectiveness of cefuroxime has been demonstrated in clinical studies.

Pharmacokinetics

Suction

The maximum concentration of cefuroxime in the blood plasma after intramuscular administration is observed in the period from 30 to 45 minutes.

Distribution

33–50% of the drug is bound to plasma proteins (depending on the technique used).

Concentrations of cefuroxime exceeding the minimum inhibitory concentration for most microorganisms can be achieved in bone tissue, synovial and intraocular fluids. Cefuroxime penetrates the blood-brain barrier during inflammation of the meninges.

Metabolism

Cefuroxime is not metabolized and is eliminated by glomerular filtration and tubular secretion.

Removal

The serum half-life of cefuroxime after intramuscular or intravenous administration is approximately 70 minutes. In newborns, the half-life of cefuroxime may be 3–5 times longer than in adults.

Concomitant administration of probenecid prolongs the excretion of cefuroxime, resulting in an increase in the maximum serum concentration of cefuroxime.

Within 24 hours after parenteral administration, cefuroxime is almost completely (85–90%) excreted unchanged through the kidneys, with most of the drug being eliminated in the first 6 hours.

Serum concentrations of cefuroxime decrease with dialysis/

Special instructions

Antibiotics of the cephalosporin group in high doses should be prescribed with caution to patients receiving concomitant therapy with strong diuretics such as furosemide or aminoglycosides, since the risk of renal failure increases. As a result, it is necessary to monitor renal function when using this combination of drugs, especially in elderly patients and in patients with a history of kidney disease (see section “Dosage and Administration”).

As with other therapeutic regimens, mild to moderate hearing loss was observed in some children when treating meningitis with Cefurus®. As with treatment with other antibiotics, detection of Haemophilus influenzae in the cerebrospinal fluid can be detected from 18 to 36 hours after injection, but the clinical significance of this phenomenon is not clear.

As with other antibiotics, the growth of Candida fungi may occur when using cefuroxime. Long-term therapy with the drug may lead to overgrowth of other non-susceptible microorganisms (for example, enterococci and Clostridium difficile), which may require discontinuation of the course of treatment with the drug.

Cases of pseudomembranous colitis have been described when taking antibiotics, the severity of which can vary from mild to life-threatening. Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after antibiotic use. If diarrhea is prolonged or severe, or the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be examined.

In step therapy, the time to switch to oral therapy is determined by the severity of the infection, the patient’s clinical condition, and the sensitivity of the pathogen. If there is no clinical improvement within 72 hours from the start of treatment, the parenteral course of therapy should be continued.

Before starting step therapy, you must read the instructions for use of the dosage form of the drug for oral administration.

The drug Cefurus® does not affect the results of determining glucose in urine using enzymatic methods.

When using other methods (Benedict, Fehling, Clinitest), an interaction may be observed, which, however, does not lead to false-positive results, as was observed with some other cephalosporins.

In patients receiving Cefurus®, it is recommended to use the glucose oxidase or hexokinase method to determine blood/plasma glucose levels.

The drug Cefurus® does not affect the quantitative determination of creatinine by the alkaline picrate method.

Introduction into the eye chamber and ophthalmic toxicity

Serious ophthalmologic toxicities, including corneal opacification, retinal toxicity, and visual impairment, have been reported following off-label intraocular administration of Cefurus®.

The drug Cefurus® should not be injected into the chamber of the eye.

Impact on the ability to drive vehicles and machinery

The use of cefuroxime does not affect the ability to drive vehicles or operate machinery.

Active ingredient

Cefuroxime

Composition

For 1 bottle:

Active ingredient:

Cefuroxime sodium – 1.578 g (in terms of cefuroxime – 1.5 g).

Pregnancy

There is no data on the development of embryotoxic or teratogenic effects of cefuroxime.

During pregnancy, the drug is used only if the expected benefit to the mother outweighs the risk to the fetus.

Cefuroxime is excreted in breast milk. If it is necessary to prescribe the drug during lactation, caution should be exercised.

Contraindications

History of hypersensitivity to cephalosporins, penicillins and carbapenems.

With caution

Should be used with caution in renal failure; a history of gastrointestinal tract diseases, such as ulcerative colitis; if necessary, combined administration of high doses of the drug with loop diuretics and aminoglycosides; in early pregnancy and lactation, as well as in newborns (especially premature babies).

Side Effects

Adverse reactions presented below are listed according to the damage to organs and organ systems and frequency of occurrence. All of the following adverse reactions are presented in accordance with the MedDRA classification by organs and systems according to their frequency: very often (≥1/10), often (≥1/100 and <1/10), infrequently (≥1/1000 and <1/100), rarely (≥1/10000 and <1/1000), very rarely (<1/10000 including individual cases).

Infectious and parasitic diseases

Rarely – candidiasis of the oral cavity and mucous membranes.

Blood and lymphatic system disorders

Often – neutropenia, eosinophilia;

Uncommon: leukopenia, decreased hemoglobin level, positive Coombs test;

Rarely – thrombocytopenia;

Very rarely – hemolytic anemia.

Cephalosporins as a class tend to be absorbed onto the surface of the red blood cell membrane and react with anti-drug antibodies, resulting in a positive Coombs test (which may interfere with cross-compatibility) and very rarely, hemolytic anemia.

Immune system disorders

Hypersensitivity reactions including:

Rarely – drug fever;

Very rarely – interstitial nephritis, anaphylaxis, cutaneous vasculitis.

See also: Renal and urinary tract disorders.

Gastrointestinal disorders

Uncommon: gastrointestinal upset;

Very rarely – pseudomembranous colitis (see section “Special instructions”).

Disorders of the liver and biliary tract

Often – a transient increase in the activity of liver enzymes;

Uncommon: transient increase in bilirubin concentration.

These adverse reactions occur in patients with a history of liver disease, but no symptoms of liver damage were noted.

Skin and subcutaneous tissue disorders

Uncommon: skin rash, urticaria and itching;

Very rarely – erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

See also: Immune system disorders.

Renal and urinary tract disorders

Very rarely – increased serum creatinine concentration, increased residual nitrogen in the blood, decreased creatinine clearance (see section “Special Instructions”).

Also see Immune System Disorders.

Hearing and labyrinth disorders

Mild or moderate hearing loss in children during treatment of meningitis.

General and administration site disorders

Common: injection site reactions, which may include soreness or thrombophlebitis. Soreness at the site of intramuscular injection, which is more likely when high doses are administered (this is not usually a reason to discontinue the drug).

Interaction

Concomitant use with loop diuretics (furosemide) and aminoglycosides slows down tubular secretion, reduces renal clearance, increases plasma concentrations and increases the half-life of cefuroxime, which increases the risk of nephrotoxic effects.

Cefuroxime in combination with aminoglycosides acts additively, but sometimes synergistic action can be observed. Cefuroxime cannot be mixed in the same syringe with aminoglycosides due to pharmaceutical incompatibility; if simultaneous use is necessary, they should be administered to different parts of the body.

Solution compatibility

When mixing a solution of Cefurus® (1.5 g in 15 ml of water for injection) and metronidazole (500 mg/100 ml), both components remain active for up to 24 hours at a temperature not exceeding 25 °C.

The drug Cefurus® in a dose of 1.5 g is compatible with azlocillin solution (1 g in 15 ml or 5 g in 50 ml); both components remain active for up to 24 hours at a temperature of about 4 °C or up to 6 hours at a temperature not exceeding 25 °C.

A solution of Cefurus® (5 mg/ml) in a 5% or 10% xylitol solution can be stored for up to 24 hours at a temperature not exceeding 25 °C.

The solution of Cefurus® is compatible with aqueous solutions containing up to 10 mg/ml lidocaine hydrochloride.

The drug Cefurus® is compatible with the most widely used infusion solutions. When mixed with the following solutions, the drug is stable for up to 24 hours at room temperature:

– 0.9% sodium chloride solution;

– 5% dextrose solution;

– 0.18% sodium chloride solution and 4% dextrose solution for injection;

– 5% dextrose solution and 0.9% sodium chloride solution;

– 5% dextrose solution and 0.45% sodium chloride solution;

– 5% dextrose solution and 0.225% sodium chloride solution;

– 10% dextrose solution for injection.

Cefuroxime solutions prepared using Ringer’s solution, lactated Ringer’s solution and Hartmann’s solution should be administered immediately after preparation.

The stability of cefuroxime sodium in 0.9% sodium chloride solution and 5% dextrose solution is not affected in the presence of hydrocortisone sodium phosphate.

Cefurus® is compatible with the following drugs when administered as an intravenous infusion and is stable for 24 hours at room temperature:

– heparin (10 U/ml and 50 U/ml) in 0.9% sodium chloride solution;

– potassium chloride (10 mEq/l and 40 mEq/l) in 0.9% sodium chloride solution.

A 2.74% sodium bicarbonate solution has a pH value that significantly affects the color of the cefuroxime solution, so it is not recommended for use in the preparation of drug solutions. However, if the patient is receiving sodium bicarbonate by infusion, cefuroxime can be injected directly into the infusion line if necessary.

Overdose

Symptoms: Increased excitability of the cerebral cortex with the development of seizures.

Treatment: Symptomatic; in severe cases, hemodialysis and peritoneal dialysis are indicated.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Manufacturer

Sintez, Russia