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 cefuroxime-sensitive bacteria, and in cases where the pathogen is not yet identified:

– Lower respiratory tract infections, such as bacterial pneumonia, acute bacterial bronchitis and exacerbation of chronic bronchitis, infected bronchiectasis, lung abscess, postoperative chest infections;

– ENT infections, such as otitis media, sinusitis, tonsillitis, pharyngitis;

– Urinary tract infections, such as acute and chronic pyelonephritis, cystitis, asymptomatic bacteriuria;

– gonorrhea;

– skin and soft tissue infections, such as cellulitis, rye, and wound infections;

– bone and joint infections, such as osteomyelitis and septic arthritis;

– obstetric and gynecological infections, also as pelvic inflammatory diseases;

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

– prevention of infectious complications during abdominal, pelvic, orthopedic, heart, lung, esophageal and vascular surgeries – where there is an increased risk of infectious complications.

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

If necessary, cefuroxime may be used for stepped therapy with conversion to oral cefuroxime axetil, primarily for the treatment of pneumonia and exacerbations of chronic bronchitis.

Active ingredient

Composition

For 1 vial:

Active substance:

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

How to take, the dosage

Interaction

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

Cefuroxime in combination with aminoglycosides acts additively, but sometimes synergism may be observed. Cefuroxime should not be mixed in the same syringe with aminoglycosides due to pharmaceutical incompatibility; if simultaneous use is necessary, they should be injected in different parts of the body.

Mixing a solution of Cefurox® (1.5 g in 15 ml of water for injection) with metronidazole (500 mg/100 ml) will keep both components active for up to 24 hours at a temperature not exceeding 25 °C.

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 approximately 4 °C or up to 6 hours at temperatures not exceeding 25 °C.

The solution of Cefurus® (5 mg/ml) in 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.

Cefurus® is compatible with the most commonly 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 with Ringer’s solution, Ringer’s lactate solution and Hartmann’s solution should be administered immediately after preparation.

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

Cefurus® is compatible with the following medicinal products when administered as 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.

Sodium bicarbonate 2.74% solution has a pH value that significantly affects the color of the cefuroxime solution, so it is not recommended for preparing solutions of the drug. However, if the patient is administered sodium bicarbonate solution by infusion, cefuroxime can be injected directly into the tube of the infusion system if necessary.

Special Instructions

High-dose cephalosporin antibiotics should be used with caution in patients receiving concomitant therapy with strong diuretics, such as furosemide or aminoglycosides, because of the increased risk of renal failure. Due to this, renal function should be monitored when using such a combination of drugs, especially in elderly patients and in patients with a history of renal disease (see section “Dosage and administration”).

As with other therapeutic regimens, mild to moderate hearing loss has been reported in some children during treatment with Cefurus® for meningitis. As with other antibiotic treatments, the detection of Haemophilus influenzae in cerebrospinal fluid can be detected from 18 to 36 hours after injection, but the clinical significance of this phenomenon is unclear.

As with other antibiotics, growth of Candida fungi may be observed with the use of cefuroxime. Prolonged therapy with the drug may lead to overgrowth of other insensitive microorganisms (e.g., enterococci and Clostridium difficile), and discontinuation of treatment with the drug may be required.

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

In step therapy, the timing of transition to oral therapy is determined by the severity of the infection, the clinical condition of the patient and the sensitivity of the pathogen. If there is no clinical improvement within 72 hours of treatment initiation, parenteral therapy must be continued.

You should read the instructions for use for the oral dosage form before starting step therapy.

The drug Cefurus® has no effect on the results of urine glucose determination using enzymatic methods.

When using other methods (Benedicta, Fehling, Clinitest) there may be interaction, which, however, does not lead to false positive results as 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® has no effect on the quantitative determination of creatinine by the alkaline-precision method.

Injection into the chamber of the eye and ophthalmic toxicity

Serious ophthalmic toxicity, including corneal opacity, retinal toxicity and visual impairment, have been reported following off-label use of Cefurus® with injection into the chamber of the eye.

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

Impact on ability to drive vehicles, machinery

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

Contraindications

Hypersensitivity to cephalosporins, penicillins and carbapenems in the history.

With caution

We should use with caution in renal failure; history of gastrointestinal diseases such as nonspecific ulcerative colitis; If high doses of the drug must be combined with loop diuretics and aminoglycosides; in early pregnancy and lactation, and in newborns (especially premature infants).

Side effects

The adverse reactions presented below are listed according to organ and system involvement and frequency of occurrence. All adverse reactions listed below are presented according to MedDRA organ and system classification according to their frequency: very common (≥1/10), common (≥1/100 and < 1/10), infrequent (≥1/1000 and < 1/100), rare (≥1/10000 and < 1/1000), very rare (< 1/10000 including individual cases).

Infectious and parasitic diseases

Rarely, candidiasis of the oral cavity and mucous membranes.

Disorders of blood and lymphatic system

Often – neutropenia, eosinophilia;

Infrequent – leukopenia, decreased hemoglobin level, positive Coombs test;

Rarely – thrombocytopenia;

Very rarely – hemolytic anemia.

The cephalosporins as a class tend to be absorbed onto the surface of the red blood cell membrane and interact with antibodies to the drug, resulting in a positive Coombs test (which can affect cross-compatibility) and very rarely, hemolytic anemia.

Immune system disorders

Hypersensitivity reactions, including:

Rarely – drug fever;

Very rarely – interstitial nephritis, anaphylaxis, cutaneous vasculitis.

Also see. “Renal and urinary tract disorders.

Gastrointestinal tract disorders

Infrequent – gastrointestinal disorder;

Very rare – pseudomembranous colitis (see section “Special indications”).

Hepatic and biliary tract disorders

Often – transient increase of “hepatic” enzymes activity;

Infrequent – transient increase of bilirubin concentration.

These adverse reactions occur in patients with a history of liver disease, but no symptoms of liver damage have been reported.

Skin and subcutaneous tissue disorders

Infrequent – skin rash, urticaria and itching;

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

Also see immune system disorders.

Renal and urinary tract disorders

Very rare – increase of serum creatinine concentration, increase of residual nitrogen in blood, decrease of creatinine clearance (see section “Special indications”).

Also see. “Immune system disorders.

Hearing and labyrinth disorders

Mild to moderate hearing loss in children with treatment of meningitis.

General disorders and disorders at the injection site

Often, reactions at the injection site, which may include soreness or thrombophlebitis. Soreness at the site of intramuscular injection, which is more likely with high doses (this is not usually a reason to withdraw the drug).

Overdose

Symptoms: Increased cortical excitability with the development of convulsions.

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

Pregnancy use

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

In pregnancy, the drug is used only if the estimated benefit to the mother exceeds the risk to the fetus.

Cefuroxime is excreted with the breast milk. Caution should be exercised if it is necessary to prescribe the drug during lactation.