Zinnat granules granules for suspension preparation 125 mg/5 ml bottle 100 ml suspension

Instructions Zinnat granules granules for suspension preparation 125 mg/5 ml bottle 100 ml suspension

Composition

active ingredient: cefuroxime;

5 ml of the finished suspension in a vial contain cefuroxime (in the form of cefuroxime axetil) 125 mg or 250 mg;

excipients: povidone K30, stearic acid, sucrose, fruit flavoring, aspartame (E 951), xanthan gum, acesulfame potassium.

Dosage form

Granules for suspension preparation.

Main physicochemical properties: white or almost white loose granules.

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 exhibits activity 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:

*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 absorption of Zinnat suspension increases when taken with food. The absorption rate of cefuroxime suspension is lower than that of tablets, which leads to lower plasma levels of the drug and reduced systemic bioavailability. The maximum serum level of cefuroxime is observed approximately 2-3 hours after administration. 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 unchanged by the kidneys 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 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

Drugs that reduce the acidity of gastric juice may reduce the bioavailability of Zinnat and have the property of minimizing the effect of accelerating the absorption of the drug after eating.

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.

A positive Coombs test has been reported with cephalosporin therapy. 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 sometimes fatal cases of hypersensitivity reactions have been reported. If severe hypersensitivity reactions occur, cefuroxime treatment 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.

Particular caution should be exercised in patients with a history of allergic reactions to penicillins or other beta-lactam antibiotics.

The use of cefuroxime axetil (as with other antibiotics) may result in overgrowth of Candida. Prolonged use may also result in overgrowth of other non-susceptible organisms (e.g. Enterococci, Clostridium difficile), which may necessitate discontinuation of treatment.

Pseudomembranous colitis can develop with antibiotics, ranging from mild to life-threatening. It is therefore important to keep this in mind if patients develop diarrhea during or after antibiotic therapy. If prolonged or severe diarrhea occurs or the patient experiences severe cramping abdominal pain, treatment should be discontinued immediately and the patient should be carefully monitored.

The granules for the preparation of suspension contain sucrose, which should be taken into account when prescribing the drug to patients with diabetes. Granules for the preparation of oral suspension 125 mg/5 ml contain 3 g of sucrose per 5 ml dose. Granules for the preparation of oral suspension 250 mg/5 ml contain 2.3 g of sucrose per 5 ml dose.

During the treatment of Lyme disease with Zinnat, a Jarisch-Herxheimer reaction was observed, which arose directly as a result of the bactericidal action of Zinnat on the microorganism that causes Lyme disease, the spirochete Borrelia burgdorferi. The patient should be aware that this is a common occurrence during antibiotic therapy for Lyme disease and does not require treatment.

The suspension contains aspartame, which is a source of phenylalanine, and therefore should not be used to treat patients with phenylketonuria.

When sequential therapy is used, the timing of the change 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 instructions for medical use of cefuroxime sodium should be consulted.

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 foetal 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, adverse reactions are 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 human fertility. 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.

The usual duration of treatment is 7 days (can be from 5 to 10 days).

For better absorption, it is recommended to take the drug in suspension form with 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

Children (< 40 kg) Table 2

For children from 3 months of age weighing less than 40 kg, the dosage regimen is adjusted according to body weight or age of the child. For children from 3 months to 18 years of age, the recommended dose is 10 mg/kg body weight 2 times a day for most infections (maximum daily dose 250 mg). For otitis media or more serious infections, the recommended dose is 15 mg/kg body weight 2 times a day (maximum daily dose 500 mg).

For the convenience of using the multidose suspension 125 mg/5 ml or 250 mg/5 ml, two tables (3, 4) are provided below, which allow for a simplified adjustment of the dose of the drug (for example, using a 5 ml measuring spoon with an additional 2.5 ml level) according to age and dosage form.

Table 3

10 mg/kg (twice daily) for most infections

Table 4

15 mg/kg (2 times a day) for the treatment of otitis media and severe infections

Cefuroxime is also available as a sodium salt for parenteral administration (Zinacef). This allows for sequential use of different forms of the same antibiotic when it is clinically appropriate to switch from parenteral to oral administration.

The duration of both parenteral and oral treatment is determined by 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, it is recommended that the dose of cefuroxime be reduced to compensate for its slower excretion (see Table 5).

Table 5

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 existing hepatic impairment will not affect the pharmacokinetics of cefuroxime.

Instructions for dissolving granules in the vial:

Immediately after reconstitution, the vial of suspension should be refrigerated at 2-8°C (do not freeze) and left for at least 1 hour before administering the first dose. The reconstituted suspension can be stored for up to 10 days when stored in a refrigerator at 2-8°C.

Always shake the bottle well before use. Use the measuring spoon provided to apply each dose.

If desired, the suspension dissolved in the vial can be further diluted with cold fruit juice or milk immediately before use and applied immediately after dilution.

Children

There is no experience with the use of Zinnat for the treatment of children under 3 months of age.

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

Adverse reactions to cefuroxime axetil are mild and generally reversible.

The frequency categories for the adverse reactions listed below are estimates, as for most events (e.g. from placebo-controlled studies) adequate data to calculate a precise frequency are not available. In addition, the frequency of adverse reactions associated with the use of cefuroxime axetil may vary depending on the indication for use.

To determine the frequency of adverse reactions from very common to rare, data from large clinical trials were used. The frequency of all other adverse reactions (i.e. those occurring with a frequency of < 1/10,000) was mainly determined on the basis of post-marketing data. The resulting frequency is more likely to be an indicator of reporting than the true frequency of the event. Data from placebo-controlled studies are not available. The frequency category calculated from the results of clinical trials is based on data related to the drug (which were assessed by the investigator).

The adverse reactions listed below are classified by system organ class and frequency of occurrence. The frequency categories are: 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) and not known (cannot be estimated from the available data).

Infections and infestations

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 rash.

Rare: urticaria, itching.

Very rare: drug fever, serum sickness, anaphylaxis.

Unknown: Jarisch-Herxheimer reaction.

From the nervous system

Common: headache, dizziness.

Gastrointestinal 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 elevations in liver enzymes (ALT, AST, LDH), usually reversible.

Very rare: jaundice (mainly cholestatic), hepatitis.

Skin and subcutaneous tissue disorders

Very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (exanthematous necrolysis) (see "Immune system disorders").

Not known: angioedema.

Children

The safety profile of cefuroxime in children is similar to that in adult patients.

Expiration date

After dissolution, the shelf life of the suspension in the vial is up to 10 days when stored in a refrigerator at a temperature of 2-8 °C.

Storage conditions

Store below 30°C. After reconstitution, store the suspension in a refrigerator at 2-8°C. Keep out of the reach of children.

Packaging

Granules for preparation of 100 ml suspension in a dark glass bottle with a lid and a protective membrane, with a plastic measuring cap on the lid. The bottle together with a measuring cap and a measuring spoon 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.