Zinnate, 125 mg/5 ml

Pharmacological action – broad spectrum antibacterial (bactericidal).

Pharmacodynamics

Cefuroxime axetil is a precursor of cefuroxime, which refers to cephalosporin antibiotics of II generation. Cefuroxime is active against a wide range of pathogens, including strains producing β-lactamases.

Cefuroxime is resistant to the action of bacterial β-lactamases, so it is effective against ampicillin-resistant or 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.

Cefuroxime is generally active in vitro against the following microorganisms.

Literate aerobes: Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae (including penicillinase producing and non-producing strains); Escherichia coli, Klebsiella spp, Proteus mirabilis, Providencia spp.

Gram-positive aerobes: Staphylococcus aureus (including penicillinase-producing strains but excluding methicillin-resistant strains), Staphylococcus epidermidis (including penicillinase-producing strains, but excluding strains resistant to methicillin), Streptococcus pyogenes (and other beta-hemolytic streptococci), Streptococcus pneumoniae, group B streptococci (Streptococcus agalactiae).

Anaerobes: gram-positive and gram-negative cocci (including species of the genera Peptococcus spp. and Peptostreptococcus spp.), gram-positive bacilli (including species of the genus Clostridium spp, except Clostridium difficile, Propionibacterium spp.), Gram-negative bacilli (including Bacteroides spp. and species of the genus Fusobacterium spp.), Gram-negative spirochetes (including Borrelia spp.).

The following microorganisms are insensitive to cefuroxime.

Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, Legionella spp.

Some strains of the following genera are insensitive to cefuroxime.

Enterococcus (Streptococcus) faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp., Bacteroides fragilis.

Pharmacokinetics

After oral administration cefuroxime axetil is slowly absorbed from the GI tract and rapidly hydrolyzed in the small intestine mucosa and blood with release of cefuroxime. Cefuroxime penetrates through the BBB, the placenta and is excreted with breast milk. Cefuroxime axetil is optimally absorbed if the drug is taken immediately after meals.

In addition for film-coated tablets. Cmax of cefuroxime (2.9 mg/L for the 125 mg dose and 4.4 mg/L for the 250 mg dose) is observed in approximately 2.4 h when the drug is taken after meals.

In addition for granules for preparation of oral suspension. Cmax of cefuroxime (2-3 mg/L for 125 mg dose and 4-6 mg/L for 250 mg dose) is observed in approximately 2-3 hours when the drug is taken after meals.

Distribution

The binding to plasma proteins is approximately 33-50%.

Metabolism

Cefuroxime is not metabolized.

The T1/2 is 1-1.5 h. Cefuroxime is excreted by glomerular filtration and tubular secretion. When concomitant administration of probenecid the AUC is increased by 50%. Serum concentrations of cefuroxime decrease with dialysis.

Indications

Cefuroxime axetil is a prodrug of oral cefuroxime antibiotic form with bactericidal action against a wide range of Gram-positive and Gram-negative bacteria. Cefuroxime is resistant to the action of β-lactamases.

The drug is indicated for treatment of infectious and inflammatory diseases caused by cefuroxime-sensitive bacteria:

Infections of the upper respiratory tract, ENT organs, such as otitis media, sinusitis, tonsillitis and pharyngitis;

Lower respiratory tract infections, such as pneumonia, acute bacterial bronchitis and exacerbation of chronic bronchitis;

Infections of the urinary tract, such as pyelonephritis, cystitis, and urethritis;

Infections of the skin and soft tissue, such as furunculosis, pyoderma, and impetigo;

Gonorrhea: acute uncomplicated gonorrheal urethritis and cervicitis;

The treatment of borreliosis (Lyme disease) in the early stages and the prevention of the later stages of this disease in adults and children over 12 years old.

Cefuroxime is also available as sodium salt (Zinacef®) for parenteral administration. Transition from parenteral to oral cefuroxime is recommended as part of step therapy. Step therapy is indicated in the treatment of pneumonia and in exacerbations of chronic bronchitis.

Active ingredient

Composition

5 ml contains cefuroxime 125 mg;

excipients:

stearic acid,

sucrose,

potassium acesulfame,

aspartame,

How to take, the dosage

Children. There are no data of clinical trials concerning Zinnat® usage in children under 3 months old.

If a fixed dose is preferred, in most infections it is recommended to take 125 mg 2 times a day. In children 2 years of age and older for middle otitis media or more severe infections, 250 mg 2 times a day is prescribed; the maximum daily dose is 500 mg.

In the treatment of infants and children it may be necessary to calculate the dose according to body weight and age. In most infections, the dose for infants and children from 3 months to 12 years of age is 10 mg/kg 2 times a day, but not more than 250 mg/day. For otitis media and more severe infections, the recommended dose is 15 mg/kg 2 times a day, but not more than 500 mg/day.

Interaction

Drugs that reduce gastric acidity may decrease the bioavailability of cefuroxime when compared with that observed following an empty stomach dose and may also offset the effect of increased absorption of the drug after a meal.

In common with other antibiotics, Zinnate® may affect the gut flora, resulting in decreased estrogen reabsorption and thus decreased efficacy of oral hormonal combination contraceptives.

The ferricyanide test may show false negative results, so it is recommended to use glucose oxidase or hexokinase methods to determine blood glucose and/or plasma levels.

The drug Zinnate® has no effect on the quantitative determination of creatinine by the alkaline-precision method.

Concomitant administration with loop diuretics slows down tubular secretion, decreases renal clearance, increases plasma concentrations and increases T1/2 of cefuroxime.

Concomitant administration with aminoglycosides and diuretics increases the risk of nephrotoxic effects.

Special Instructions

Caution should be exercised when prescribing the drug in patients with a history of allergic reactions to beta-lactam antibiotics.

Key renal function should be monitored during treatment, especially in patients receiving a high dose of the drug.

When using Zinnate® a false positive urine glucose reaction is possible.

As with other antibiotics, prolonged use of Zinnate® may cause excessive growth of Candida fungi. Prolonged use may cause growth of other resistant microorganisms (Enterococci and Clostridium difficile), which may require discontinuing treatment.

Pseudomembranous colitis has been observed with broad-spectrum antibiotics, so differential diagnosis of pseudomembranous colitis should be made in patients with severe diarrhea that occurred during or after antibiotic treatment.

Jarisch-Herxheimer reaction has been observed in borreliosis (Lyme disease) while taking Zinnate® and is caused by bactericidal activity of the drug against spirochaete Borrelia burgdorferi. Patients should be informed that these symptoms are a typical consequence of antibiotic treatment for this disease.

If clinical effect is not achieved within 72 hours of treatment initiation, parenteral therapy should be continued.

Information regarding the sodium salt of cefuroxime (Zinacef®) should be obtained from reference books before starting step therapy.

The tablets of Zinnat® should not be crushed or broken. Therefore, this drug form is not suitable for treating patients with swallowing difficulties, including small children who cannot swallow the whole tablet.

Pellets for preparation of suspension for oral administration. Consider the sucrose content in Zinnat® suspension when treating patients with diabetes mellitus.

5 ml of Zinnat® suspension contains 0.25 IU.

Impact on the ability to drive vehicles and operate machinery. Since cefuroxime axetil may cause dizziness, patients should be warned about the precautionary measures when driving vehicles or operating moving mechanisms.

Contraindications

– hypersensitivity to β-lactam antibiotics (in particular to cephalosporin antibiotics, penicillins and carbapenems in the history).

– hypersensitivity to aspartame;

– phenylketonuria;

– childhood under 3 months.

With caution: renal function disorders; Gastrointestinal diseases (including anamnesis and ulcerative colitis); pregnant women; lactation period.

Side effects

Adverse reactions with cefuroxime axetil are usually mild, transient and reversible.

The undesired phenomena presented below are listed according to the anatomico-physiological classification and frequency of occurrence. The frequency of occurrence is defined as follows: very frequently, ≥1/10; frequently, ≥1/100 and < 1/10; infrequently, ≥1/1000 and < 1/100; rarely, ≥1/10000 and < 1/1000; very rarely, < 1/10000, including individual cases. Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.

Infections: often – superinfection with fungi of the genus Candida.

Hematopoietic and lymphatic system disorders: frequently – eosinophilia; infrequently – false positive Coombs test, thrombocytopenia, leukopenia (sometimes severe); very rarely – hemolytic anemia. Cephalosporins are absorbed on the surface of the cell membrane of red blood cells, binding to antibodies to cephalosporins, which leads to false positive Coombs test results and in very rare cases – hemolytic anemia.

The immune system: hypersensitivity reactions, including: infrequent – skin rash; rare – urticaria, pruritus; very rare – drug fever, serum sickness, anaphylaxis.

Nervous system disorders: often – headache, dizziness.

Gastrointestinal disorders: frequent – gastrointestinal disorders, including diarrhea, nausea, abdominal pain; infrequent – vomiting; rarely – pseudomembranous colitis.

Hepatic and biliary tract disorders: often – transient increase of liver enzymes activity (ALT, AST, LDH); very rarely – jaundice (predominantly cholestatic), hepatitis.

Skin and subcutaneous fat: very rare – erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Overdose

Symptoms: increased cerebral excitability with the development of seizures.

Treatment: symptomatic. Serum concentrations of cefuroxime are reduced by hemodialysis and peritoneal dialysis.

Pregnancy use

The drug Zinnate® should be used if the potential benefit to the mother is greater than the potential risk to the child.

There is no experimental evidence of embryopathic or teratogenic effects of cefuroxime axetil, but as with other drugs, caution should be exercised when prescribing it in early pregnancy.

Caution should be exercised when prescribing it to nursing mothers because the drug is detected in breast milk.

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