Zinnat

I N S T R U C T I O N for medical use of the medicinal product Zinnat®

Composition:

Active substance: cefuroxime;

1 tablet contains cefuroxime (as cefuroxime axetil) 125 mg or 250 mg or 500 mg;

Excipients: microcrystalline cellulose, sodium croscarmellose (type A), sodium lauryl sulfate, hydrogenated vegetable oil, colloidal anhydrous silicon dioxide, hypromellose, propylene glycol, methylparahydroxybenzoate (E 218), propylparahydroxybenzoate (E 216), Opaspray White M-1-7120J (containing sodium benzoate (E 211)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: film-coated, capsule-shaped, biconvex tablets, white or almost white; with marking «GX ES5» on one side for 125 mg tablets;

film-coated, capsule-shaped, biconvex tablets, white or almost white; with marking «GX ES7» on one side for 250 mg tablets;

film-coated, capsule-shaped, biconvex tablets, white or almost white; with marking «GX EG2» on one side for 500 mg tablets.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Beta-lactam antibiotics. ATC code J01D C02.

Pharmacological properties.

Pharmacodynamics.

Cefuroxime axetil is an oral form of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to the action of most beta-lactamases and exhibits activity against a broad spectrum of Gram-positive and Gram-negative microorganisms.

The bactericidal effect of cefuroxime results from the inhibition of microbial cell wall synthesis.

Acquired resistance to the antibiotic varies among different regions and may change over time, with significant differences possible among individual strains. Local data on antibiotic susceptibility should be consulted whenever available, especially when treating severe infections.

Cefuroxime generally has in vitro activity against the following microorganisms:

*All methicillin-resistant S. aureus are insensitive to cefuroxime.

Pharmacokinetics.

After oral administration, cefuroxime axetil is absorbed in the intestine, hydrolyzed in the intestinal mucosa, and enters the bloodstream as cefuroxime.

Optimal absorption is observed immediately after food intake. Maximum serum concentration of cefuroxime occurs approximately 2–3 hours after administration. The elimination half-life of the drug is approximately 1–1.5 hours. Protein binding ranges from 33% to 55%, depending on the method of determination. Cefuroxime is excreted unchanged by the kidneys via tubular secretion and glomerular filtration.

Concomitant administration of probenecid increases the area under the serum concentration-time curve by 50%.

Serum levels of cefuroxime decrease during dialysis.

Clinical characteristics.

Indications.

Zinnat is indicated for the treatment of the following infections in adults and children aged 3 months and older:

• Acute streptococcal tonsillitis and pharyngitis.
• Acute bacterial sinusitis.
• Acute otitis media.
• Exacerbations of chronic bronchitis caused by pathogens sensitive to cefuroxime axetil.
• Cystitis.
• Pyelonephritis.
• Uncomplicated skin and soft tissue infections.
• Early manifestations of Lyme disease.

Contraindications.

Hypersensitivity to cephalosporin antibiotics, cefuroxime, or to any component of the drug. Severe hypersensitivity reactions in history (e.g., anaphylactic reactions) to other types of beta-lactam antibiotics (penicillins, monobactams, and carbapenems).

Interaction with other medicinal products and other forms of interactions.

Medicinal products that reduce gastric acidity may decrease the bioavailability of Zinnat and may eliminate the enhanced absorption effect observed after food intake.

Like other antibiotics, Zinnat may affect intestinal flora, leading to reduced reabsorption of estrogens and decreased efficacy of combined oral contraceptives.

Since a pseudonegative result may occur in the ferricyanide test, it is recommended to use glucose oxidase or hexokinase methods for determining glucose levels in blood and plasma in patients receiving cefuroxime axetil. Cefuroxime does not affect the alkaline picrate assay for creatinine determination.

Concomitant administration with probenecid leads to a significant reduction in 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 increased INR (International Normalized Ratio).

Serum cefuroxime levels are reduced by dialysis.

During treatment with cephalosporins, positive Coombs' test results have been reported. This phenomenon may affect cross-matching blood compatibility tests.

Special precautions for use.

Hypersensitivity reactions

Particular caution is required 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 antimicrobial agents, severe and occasionally fatal hypersensitivity reactions have been reported. In the event of severe hypersensitivity reactions, cefuroxime therapy should be discontinued immediately and appropriate emergency medical treatment should be provided.

Prior to initiating therapy, it is necessary to determine whether the patient has previously experienced severe hypersensitivity reactions to cefuroxime, other cephalosporins, or other types of beta-lactam drugs. Cefuroxime should be administered with caution in patients with a history of mild hypersensitivity reactions to other beta-lactam medicinal products.

The use of cefuroxime axetil (as with other antibiotics) may lead to overgrowth of Candida. Prolonged treatment may also result in overgrowth of other resistant microorganisms (e.g., Enterococci, Clostridium difficile), which in turn may necessitate discontinuation of therapy.

Pseudomembranous colitis, ranging from mild to life-threatening forms, may occur during antibiotic therapy. Therefore, this possibility should be considered if patients develop severe diarrhea during or after antibacterial treatment. If prolonged or pronounced diarrhea occurs, or if the patient experiences sudden colicky abdominal pain, treatment should be discontinued immediately and the patient should undergo thorough evaluation.

Jarisch–Herxheimer reaction has been observed during treatment with Zinnat for Lyme disease, which occurs directly due to the bactericidal effect of Zinnat on the causative agent of Lyme disease, the spirochete Borrelia burgdorferi. Patients should be informed that this is a common consequence of antibiotic therapy for Lyme disease, which resolves without treatment.

When performing sequential therapy, the timing of transition from parenteral to oral therapy depends on the severity of infection, the patient's clinical condition, and the susceptibility of the causative microorganism. Parenteral therapy should be continued if there is no clinical improvement within 72 hours. Before initiating sequential therapy, the relevant Instructions for Medical Use of sodium cefuroxime should be consulted.

Zinnat tablets contain parabens, which may cause allergic reactions (possibly delayed-type).

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of cefuroxime in pregnant women are limited. Animal studies have not shown any adverse effects of cefuroxime axetil on pregnancy, embryonal or fetal development, parturition, or postnatal development. Zinnat should be prescribed to pregnant women only when the potential benefit outweighs the possible risks.

Breast-feeding

Cefuroxime passes into breast milk in small amounts. When therapeutic doses are used, adverse reactions are not expected; however, the risk of diarrhea or fungal mucosal infections cannot be excluded. Therefore, due to these possible reactions, discontinuation of breastfeeding may be required. The potential sensitizing effect of the drug should also be considered. Cefuroxime may be administered during breastfeeding only after a physician has evaluated the benefit-risk ratio of its use.

Fertility

There are no data on the effect of cefuroxime axetil on fertility in humans. Reproductive function studies in animals have not shown any effect of this medicinal product on fertility.

Ability to affect reaction speed when driving vehicles or operating machinery.

Since the drug may cause dizziness, patients should be warned to exercise caution when driving vehicles or operating machinery.

Method of administration and dosage.

Sensitivity to the antibiotic varies depending on the region and may change over time. If necessary, local data on antibiotic sensitivity should be consulted.

The usual duration of treatment is 7 days (may range from 5 to 10 days).

To ensure better absorption, the drug should be taken after food.

Dosage recommendations for adults and children according to the type of infection are presented in Tables 1 and 2.

Adults and children (≥ 40 kg) Table 1

Children (< 40 kg) Table 2

Cefuroxime axetil tablets cannot be split and therefore should not be prescribed to patients who are unable to swallow them. The suspension formulation is recommended for children.

Cefuroxime axetil tablets and cefuroxime axetil granules for oral suspension are not bioequivalent; therefore, these dosage forms are not interchangeable on a milligram-to-milligram basis.

Cefuroxime is also available as the sodium salt for parenteral administration. This allows sequential therapy with the same antibiotic when switching from parenteral to oral administration, provided there are appropriate clinical indications.

Zinnat is effective for sequential treatment of exacerbations of chronic bronchitis following prior parenteral administration of Zinacef (cefuroxime sodium).

Sequential therapy

Exacerbations of chronic bronchitis: 750 mg cefuroxime 2–3 times daily (intravenously or intramuscularly) for 48–72 hours, followed by oral Zinnat 500 mg twice daily for 5–10 days.

The duration of both parenteral and oral treatment should be determined according to the severity of infection and the patient's clinical condition.

Patients with renal impairment

Cefuroxime is primarily eliminated via the kidneys. In patients with significantly impaired renal function, the dose of cefuroxime should be reduced to compensate for its slower excretion (see table below).

Patients with hepatic impairment

There are no data on the use of this medicinal product in patients with impaired liver function. Cefuroxime is primarily eliminated via the kidneys, so it is expected that impaired liver function will not affect the pharmacokinetics of cefuroxime.

Children.

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

Zinnat tablets cannot be divided; therefore, they are not prescribed to patients who are unable to swallow them. Children are recommended to be given the drug in the form of a suspension.

Overdose.

CNS irritation and neurological complications, including encephalopathy, seizures, and coma, may occur in cases of cephalosporin overdose. Symptoms of overdose may occur if the drug dose has not been appropriately adjusted in patients with impaired renal function (see sections "Dosage and administration" and "Special precautions").

Serum cefuroxime levels can be reduced by hemodialysis and peritoneal dialysis.

Side effects.

Adverse reactions associated with the use of cefuroxime axetil are generally mild and mostly reversible in nature.

The adverse reactions listed below are classified by organ systems and frequency of occurrence. Frequencies are categorized as follows:

Very common: ≥ 1 in 10,
Common: ≥ 1 in 100 to < 1 in 10,
Uncommon: ≥ 1 in 1,000 to < 1 in 100,
Rare: ≥ 1 in 10,000 to < 1 in 1,000,
Very rare: < 1 in 10,000.
Not known: frequency cannot be estimated from the available data.

Infections and infestations

Common: Overgrowth of Candida.
Not known: Overgrowth of Clostridium difficile.

Blood and lymphatic system disorders

Common: Eosinophilia.
Uncommon: Positive Coombs test, thrombocytopenia, leukopenia (sometimes profound).
Very rare: Hemolytic anemia.

Cephalosporins as a class may adsorb onto the surface of red blood cell membranes and interact with antibodies, potentially leading to a positive Coombs test (which may interfere with blood compatibility testing) and, very rarely, hemolytic anemia.

Immune system disorders

Hypersensitivity reactions, including:

Uncommon: Skin rashes.
Rare: Urticaria, pruritus.
Very rare: Drug fever, serum sickness, anaphylaxis.
Not known: Jarisch–Herxheimer reaction.

Nervous system disorders

Common: Headache, dizziness.

Gastrointestinal disorders

Common: Gastrointestinal disturbances, including diarrhea, nausea, abdominal pain.
Uncommon: Vomiting.
Rare: Pseudomembranous colitis (see section "Special precautions").

Hepatobiliary disorders

Common: Transient elevations 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 pediatric patients is consistent with that observed in adults.

Shelf life. 3 years.

Storage conditions.
Store at temperatures not exceeding 30 °C. Keep out of reach of children.

Packaging. Blister packs of 10 tablets in cardboard packaging.

Prescription status. Prescription only.

Manufacturer. Glaxo Operations UK Limited (United Kingdom).

Manufacturer's address and place of business.
Glaxo Operations UK Limited, Harmire Road, Barnard Castle, Durham, DL12 8DT, United Kingdom.