Axetine, 1.5 g

Cefuroxime

Indications

Aksetin® is indicated for the treatment of diseases 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, such as inflammatory diseases of the pelvic organs;

– other infections, including septicemia, meningitis, 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, Axetin® can be used for step-down therapy with a transition to oral therapy with a drug containing cefuroxime axetil 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 anaerobes

Haemophilus influenzae1, including ampicillin-resistant strains

Haemophilus parainfluenzae1

Moraxella catarrhalis1

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

Viridans group streptococci

Gram-negative aerobes

Bordetella pertussis

Citrobacier spp., except C. freundii

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

Escherichia coli1

Klebsiella spp., including K. pneumoniae1

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. faecalis1 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

Others

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 blood plasma after intramuscular administration (IM) 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 following intramuscular or intravenous (IV) 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 excreted 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, when treating meningitis with Axetin®, some children experienced mild to moderate hearing loss. 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 the use of other antibiotics, when using the drug Aksetin®, the growth of fungi of the genus Candida may be observed. 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 and 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 of the start of treatment, parenteral therapy should be continued.

Before starting step therapy, you must read the instructions for use of the drug Axetin®.

The drug Aksetin® 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 Axetin®, it is recommended to use the glucose oxidase or hexokinase method to determine blood/plasma glucose levels.

The drug Aksetin® 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 Axetin®. The drug Aksetin® 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 and other mechanisms.

Active ingredient

Cefuroxime

Composition

1 bottle contains:

Active substance

Cefuroxime sodium, equivalent to 750 mg cefuroxime.

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 breastfeeding, caution should be exercised.

Contraindications

History of hypersensitivity to cephalosporin antibiotics, penicillins and carbapenems.

With caution

It should be used with caution in case of renal failure, a history of gastrointestinal diseases, such as ulcerative colitis; if necessary, combined administration of high doses of the drug with loop diuretics and aminoglycosides; in early pregnancy and during breastfeeding, 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. The frequency of occurrence is defined as follows: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare (<1/10000) frequency unknown (cannot be determined based on available data).

Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.

Frequency of occurrence of adverse reactions:

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 rare: 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:

Uncommon: skin rash, urticaria, itching;

Rarely: drug fever;

Very rare: interstitial nephritis, anaphylaxis, cutaneous vasculitis.

See also sections: Skin and subcutaneous tissue disorders and Renal and urinary tract disorders.

Gastrointestinal disorders

Uncommon: gastrointestinal upset;

Very rare: pseudomembranous colitis (see section “Special instructions”).

Disorders of the liver and biliary tract

Often: transient increase in the activity of liver enzymes;

Uncommon: transient increase in bilirubin levels.

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

Skin and subcutaneous tissue disorders

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

Also see Immune System Disorders.

Renal and urinary tract disorders

Very rarely: increased serum creatinine concentration, increased residual nitrogen in the blood and decreased clearance (see section “Special Instructions”). See also Immune System Disorders.

Hearing and labyrinth disorders

Very rare: mild to moderate hearing loss in children during treatment of meningitis.

General and administration site disorders

Common: injection site reactions, which may include soreness and thrombophlebitis.

Soreness at the site of intramuscular injection is more likely with high doses, but 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.

Aksetin® in combination with aminoglycosides acts additively, but sometimes synergistic action can be observed. Aksetin® 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

The drug Aksetin® is compatible with aqueous solutions containing up to 1% lidocaine hydrochloride.

The drug Aksetin® is compatible with the most widely used infusion solutions. It remains stable when stored for 6 hours at 25°C and 24 hours at 2–8°C in the following solutions:

– 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;

– Hartmann’s solution;

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

– 0.9% sodium chloride solution;

– 5% dextrose solution for injection;

– 10% dextrose solution for injection;

– Ringer’s solution;

– lactated Ringer’s solution.

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

A freshly prepared solution for intravenous administration has a yellowish tint, while a suspension for intramuscular administration is almost white.

The solution may darken during storage, but changes in color intensity do not affect the safety of administration and the effectiveness of the drug.

Any unused medicine or waste must be disposed of in accordance with local regulations.

Overdose

Symptoms

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

Treatment

Symptomatic, hemodialysis, peritoneal dialysis.

Storage conditions

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

Keep out of the reach of children.

Shelf life

2 years.

Do not use after the expiration date stated on the package.

Manufacturer

Medokemi Ltd, Cyprus