Instructions Zinnat film-coated tablets 125 mg blister No. 10
Composition
active ingredient: cefuroxime;
1 tablet contains cefuroxime (in the form of cefuroxime axetil) 125 mg or 250 mg, or 500 mg;
excipients: microcrystalline cellulose, croscarmellose sodium (type A), sodium lauryl sulfate, hydrogenated vegetable oil, colloidal anhydrous silica, hypromellose, propylene glycol, methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), Opaspray White M-1-7120J (contains sodium benzoate (E 211)).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated, biconvex, capsule-shaped tablets, white or almost white in color; marked “GX ES5” on one side for 125 mg tablets;
Film-coated, capsule-shaped, biconvex tablets, white or almost white in colour; marked “GX ES7” on one side for 250 mg tablets;
Film-coated, capsule-shaped, biconvex tablets, white or almost white; marked “GX EG2” on one side for 500 mg tablets.
Pharmacotherapeutic group
Antimicrobials for systemic use. Beta-lactam antibiotics. ATX code J01D C02.
Pharmacological properties
Pharmacodynamics.
Cefuroxime axetil is an oral form of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most beta-lactamases and is active against a broad spectrum of gram-positive and gram-negative microorganisms.
The bactericidal effect of cefuroxime is the result of inhibition of the synthesis of the cell membrane of microorganisms.
Acquired antibiotic resistance varies between regions and can change over time, and may vary significantly for individual strains. It is advisable to consult local antibiotic susceptibility data, if available, especially when treating severe infections.
Cefuroxime is generally active against the following microorganisms in vitro:
| Sensitive microorganisms: |
Gram-positive aerobes: Staphylococcus aureus (methicillin-susceptible)* Coagulase-negative staphylococcus (methicillin-sensitive) Streptococcus pyogenes Streptococcus agalactiae |
Gram-negative aerobes: Haemophilus influenzae Haemophilus parainfluenzae Moraxella catarrhalis |
Spirochetes: Borrelia burgdorferi |
| Microorganisms whose acquired resistance may be a problem: |
Gram-positive aerobes: Streptococcus pneumoniae |
Gram-negative aerobes: Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Proteus mirabilis Proteus strains (other than P. vulgaris) Providencia strains |
Gram-positive anaerobes: Peptostreptococcus strains Propionibacterium strains |
Gram-negative anaerobes: Fusobacterium strains Bacteroides strains |
| Resistant microorganisms: |
Gram-positive aerobes: Enterococcus faecalis Enterococcus faecium |
Gram-negative aerobes: Acinetobacter strains. Campylobacter strains Morganella morganii Proteus vulgaris Pseudomonas aeruginosa Serratia marcescens |
Gram-negative anaerobes: Bacteroides fragilis |
Others: Chlamydia strains Mycoplasma strains Legionella strains |
*All methicillin-resistant S. aureus are insensitive to cefuroxime.
Pharmacokinetics.
After oral administration of cefuroxime axetil is absorbed in the intestine, hydrolyzed on the intestinal mucosa and enters the bloodstream as cefuroxime.
The optimal level of absorption is observed immediately after eating. The maximum level of cefuroxime in the blood serum is observed approximately 2-3 hours after taking the drug. The half-life of the drug is approximately 1-1.5 hours. The level of protein binding is 33-55% depending on the method of determination. Cefuroxime is excreted by the kidneys in an unchanged state by tubular secretion and glomerular filtration.
Concomitant use of probenecid increases the area under the mean serum concentration curve by 50%.
Serum cefuroxime levels are reduced by dialysis.
Indication
Zinnat is indicated for the treatment of the infections listed below in adults and children aged 3 months and older.
– Acute streptococcal tonsillitis and pharyngitis.
– Acute bacterial sinusitis.
– Acute otitis media.
– Exacerbation of chronic bronchitis caused by pathogens sensitive to cefuroxime axetil.
– Cystitis.
– Pyelonephritis.
– Uncomplicated skin and soft tissue infections.
– Early manifestations of Lyme disease.
Contraindication
Hypersensitivity to cephalosporin antibiotics, cefuroxime or to any of the excipients. History of severe hypersensitivity reactions (e.g. anaphylactic reactions) to any other type of beta-lactam antibiotic (penicillins, monobactams and carbapenems).
Interaction with other medicinal products and other types of interactions
Like other antibiotics, Zinnat may have an effect on the intestinal flora, which will lead to a decrease in the reabsorption of estrogens and a decrease in the effectiveness of combined oral contraceptives.
Since the ferrocyanide test may give a false-negative result, it is recommended that glucose oxidase or hexokinase methods be used to determine blood and plasma glucose levels in patients treated with cefuroxime axetil. Cefuroxime does not interfere with the alkaline picrate assay for creatinine.
Concomitant use with probenecid results in a significant reduction in the maximum concentration, area under the serum concentration-time curve and half-life of cefuroxime. Therefore, concomitant use with probenecid is not recommended.
Concomitant use with oral anticoagulants may lead to an increase in the INR (international normalized ratio).
Serum cefuroxime levels are reduced by dialysis.
There have been reports of positive Coombs' tests with cephalosporins. This phenomenon may interfere with cross-matching of blood.
Application features
Hypersensitivity reactions
Special caution should be exercised in patients with a history of allergic reactions to penicillins or other beta-lactam antibiotics, as there is a risk of cross-sensitivity. As with all beta-lactam antimicrobials, serious and occasionally fatal hypersensitivity reactions have been reported. In the event of a severe hypersensitivity reaction, cefuroxime should be discontinued immediately and the patient should receive appropriate emergency medical care.
Before initiating therapy, it is necessary to determine whether the patient has had a previous severe hypersensitivity reaction to cefuroxime, other cephalosporins or other types of beta-lactam drugs. Cefuroxime should be administered with caution to patients with a history of non-severe hypersensitivity reactions to other beta-lactam drugs.
The use of cefuroxime axetil (as with other antibiotics) may result in overgrowth of Candida. Prolonged treatment may also result in overgrowth of other non-susceptible organisms (e.g. Enterococci, Clostridium difficile), which may necessitate discontinuation of treatment.
Pseudomembranous colitis, which can range from mild to life-threatening, may occur with antibiotics. It is therefore important to keep this in mind if patients develop severe diarrhoea during or after antibiotic therapy. If diarrhoea is prolonged or severe or if the patient experiences severe cramping abdominal pain, treatment should be discontinued immediately and the patient should be carefully examined.
During the treatment of Lyme disease with Zinnat, a Jarisch-Herxheimer reaction has been observed, which occurs directly due to the bactericidal effect of Zinnat on the microorganism that causes Lyme disease, the spirochete Borrelia burgdorferi. Patients should be explained that this is a normal consequence of antibiotic therapy for Lyme disease, which resolves without treatment.
When sequential therapy is used, the timing of the transition from parenteral to oral therapy is determined by the severity of the infection, the clinical condition of the patient, and the susceptibility of the pathogen. If there is no clinical improvement within 72 hours, parenteral therapy should be continued. Before starting sequential therapy, the appropriate Summary of Product Characteristics for cefuroxime sodium should be consulted.
Zinnat tablets contain parabens, which can cause allergic reactions (possibly delayed).
Use during pregnancy or breastfeeding
Pregnancy
There are limited data on the use of cefuroxime in pregnant women. Animal studies have not shown any adverse effects of cefuroxime axetil on pregnancy, embryonal and fetal development, parturition, or postnatal development. Zinnat should be administered to pregnant women only if the potential benefit outweighs the potential risk.
Breast-feeding
Cefuroxime passes into breast milk in small quantities. When using therapeutic doses of the drug, the development of adverse reactions is not expected, but the risk of diarrhea or fungal infection of the mucous membranes cannot be excluded. Therefore, in connection with these reactions, it may be necessary to discontinue breastfeeding. The possibility of a sensitizing effect of the drug should also be taken into account. Cefuroxime is prescribed during breastfeeding only after a doctor has assessed the benefit-risk ratio of its use.
Fertility
There are no data on the effects of cefuroxime axetil on fertility in humans. Animal reproduction studies have not shown any effect of this medicinal product on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Since the drug may cause dizziness, patients should be warned to drive and operate other machinery with caution.
Method of administration and doses
Antibiotic susceptibility varies by region and may change over time. Local antibiotic susceptibility data should be consulted if necessary.
Usually the duration of treatment is 7 days (can be from 5 to 10 days).
For better absorption, it is recommended to take the drug after meals.
The dosage of the drug for adults and children depending on the infection is given in Tables 1, 2.
Adults and children (≥ 40 kg) Table 1
| Indications for use | Dose |
| Acute tonsillitis and pharyngitis, acute bacterial sinusitis | 250 mg 2 times a day |
| Acute otitis media | 500 mg 2 times a day |
| Exacerbation of chronic bronchitis | 500 mg 2 times a day |
| Cystitis | 250 mg 2 times a day |
| Pyelonephritis | 250 mg 2 times a day |
| Uncomplicated skin and soft tissue infections | 250 mg 2 times a day |
| Lyme disease | 500 mg 2 times a day for 14 days (therapy may last from 10 to 21 days) |
Children (< 40 kg) Table 2
| Indications for use | Dose |
| Acute tonsillitis and pharyngitis, acute bacterial sinusitis | 10 mg/kg 2 times a day, maximum dose – 125 mg 2 times a day |
| Children aged 2 years and older with otitis media or, if necessary, for more serious infections | 15 mg/kg 2 times a day, maximum dose – 250 mg 2 times a day |
| Cystitis | 15 mg/kg 2 times a day, maximum dose – 250 mg 2 times a day |
| Pyelonephritis | 15 mg/kg 2 times a day, maximum dose – 250 mg 2 times a day for 10-14 days |
| Uncomplicated skin and soft tissue infections | 15 mg/kg 2 times a day, maximum dose – 250 mg 2 times a day |
| Lyme disease | 15 mg/kg 2 times a day, maximum dose – 250 mg 2 times a day for 14 days (from 10 to 21 days) |
Zinnat tablets cannot be broken, so they are not prescribed to patients who cannot swallow them. It is recommended to prescribe the drug in the form of a suspension to children.
Cefuroxime acetyl tablets and cefuroxime acetyl granules for suspension are not bioequivalent, so these dosage forms are not interchangeable on a milligram basis.
Cefuroxime is also available as a sodium salt for parenteral use. This allows sequential therapy with a single antibiotic when switching from parenteral to oral administration, if clinically indicated.
Zinnat is effective for the sequential treatment of exacerbations of chronic bronchitis after previous parenteral administration of "Zinacef" (cefuroxime sodium).
Sequential therapy
Exacerbation of chronic bronchitis: 750 mg of cefuroxime 2-3 times a day (intravenously or intramuscularly) for 48-72 hours, followed by Zinnat 500 mg 2 times a day orally for 5-10 days.
The duration of both parenteral and oral treatment should be determined taking into account the severity of the infection and the patient's condition.
Patients with renal failure
Cefuroxime is excreted primarily by the kidneys. In patients with severe renal impairment, a reduced dose of cefuroxime is recommended to compensate for its slower excretion (see table below).
| Creatinine clearance | T1/2 (hours) | Recommended dosage |
| ≥ 30 ml/min | 1.4 – 2.4 | No dose adjustment is required (use standard dose of 125 mg to 500 mg 2 times a day) |
| 10 – 29 ml/min | 4.6 | Standard individual dose every 24 hours |
| <10 ml/min | 16.8 | Standard individual dose every 48 hours |
| During hemodialysis | 2 – 4 | One additional standard dose should be administered after each dialysis. |
Patients with liver failure
There are no data on the use of this medicinal product in patients with hepatic impairment. Cefuroxime is excreted primarily by the kidneys, therefore, it is expected that pre-existing hepatic impairment will not affect the pharmacokinetics of cefuroxime.
Children
There is no experience with the use of cefuroxime axetil in the treatment of children under 3 months of age.
Zinnat tablets cannot be broken, so they are not prescribed to patients who cannot swallow them. It is recommended to prescribe the drug in the form of a suspension to children.
Overdose
Overdose of cephalosporins may cause brain irritation and neurological complications, including encephalopathy, convulsions and coma. Symptoms of overdose may occur if the dose of the drug has not been appropriately adjusted for patients with impaired renal function (see sections "Method of administration and dosage" and "Special instructions for use").
Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.
Adverse reactions
Side effects of cefuroxime axetil are mild and mostly reversible.
Adverse reactions, information about which is given below, are classified by organ system and by frequency of occurrence. By frequency of occurrence, they are divided into the following categories:
very common ≥ 1 in 10, common ≥ 1 in 100 and < 1 in 10, uncommon ≥ 1 in 1,000 and < 1 in 100, rare ≥ 1 in 10,000 and < 1 in 1,000, very rare < 1 in 10,000.
Common: Candida overgrowth.
Not known: Clostridium difficile overgrowth.
Blood and lymphatic system disorders
Common: eosinophilia.
Uncommon: positive Coombs test, thrombocytopenia, leukopenia (sometimes profound).
Very rare: hemolytic anemia.
Cephalosporins as a class have the property of being absorbed on the surface of the erythrocyte membrane and interacting with antibodies there, which can lead to a positive Coombs test (impact on blood compatibility) and (very rarely) to hemolytic anemia.
On the part of the immune system
Hypersensitivity reactions, including
Uncommon: skin rashes.
Rare: urticaria, itching.
Very rare: drug fever, serum sickness, anaphylaxis.
Unknown: Jarisch-Herxheimer reaction.
From the nervous system
Common: headache, dizziness.
From the digestive tract
Common: Gastroenterological disorders including diarrhoea, nausea, abdominal pain.
Uncommon: vomiting.
Rare: pseudomembranous colitis (see section "Special warnings and precautions for use").
Hepatobiliary system
Common: transient increase in liver enzymes (ALT, AST, LDH).
Very rare: jaundice (mainly cholestatic), hepatitis.
Skin and subcutaneous tissue disorders
Very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (exanthematous necrolysis).
Not known: angioedema.
Children
The safety profile of cefuroxime in children is similar to that in adult patients.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.
Packaging
Blisters of 10 tablets in a cardboard box.
Vacation category
According to the recipe.
Producer
Glaxo Operations UK Limited (United Kingdom).
Location of the manufacturer and address of its place of business
Glaxo Operations UK Limited, Harmire Road, Barnard Castle, Durham, DL12 8DT, United Kingdom.
