Cefuroxime deva

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Cefuroxime Deva (Cefuroxime Deva)

Composition:

Active substance: cefuroxime;

One film-coated tablet contains cefuroxime axetil in an amount equivalent to 250 mg or 500 mg of cefuroxime;

Excipients: microcrystalline cellulose, sodium lauryl sulfate, hydrogenated vegetable oil, sodium croscarmellose, colloidal anhydrous silicon dioxide;

Coating of the tablet: Opaspray white M-1-7120, hydroxypropylmethylcellulose, propylene glycol, methylparaben, propylparaben.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, elongated tablets, film-coated, with "250" or "500" embossed on one side.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. Other beta-lactam antibiotics. Second-generation cephalosporins.

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 demonstrates 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 antibiotic susceptibility data should be consulted, if available, especially when treating severe infections.

Cefuroxime generally has in vitro activity against the following microorganisms:

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

Pharmacokinetics.

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

Optimal absorption occurs immediately after food intake. Maximum serum concentration of cefuroxime is reached 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 concentration-time curve (AUC) by 50%.

Serum levels of cefuroxime are reduced by dialysis.

Clinical characteristics.

Indications.

Cefuroxime Deva 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 any component of the drug. Severe hypersensitivity reactions (e.g., anaphylactic reactions) in medical history to any other type of beta-lactam antibiotics (penicillins, monobactams, and carbapenems).

Interaction with other medicinal products and other forms of interaction.

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

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

Since pseudonegative results may occur in the ferricyanide test, glucose oxidase or hexokinase methods are recommended for determining plasma glucose levels in patients receiving cefuroxime. Cefuroxime does not affect the alkaline picrate method for creatinine determination.

Concomitant administration with probenecid leads to a significant increase in maximum concentration, AUC, and half-life of cefuroxime. Therefore, concomitant use with probenecid is not recommended.

Concomitant use with oral anticoagulants may increase the international normalized ratio (INR).

Effect on diagnostic tests

Serum cefuroxime levels can be 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 antibiotics, serious and sometimes fatal hypersensitivity reactions have been reported. Hypersensitivity reactions progressing to Kounis syndrome – acute allergic coronary artery spasm that may lead to myocardial infarction – have been reported (see section "Adverse reactions"). In case of severe hypersensitivity reactions, treatment with cefuroxime should be discontinued immediately and appropriate emergency measures should be initiated.

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 medicinal products. Cefuroxime should be administered with caution to patients with a history of mild hypersensitivity reactions to other beta-lactam medicinal products.

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and DRESS syndrome, which may be life-threatening or fatal, have been reported in association with cefuroxime treatment (see section "Adverse reactions").

Patients should be informed about the signs and symptoms of these skin reactions, and careful monitoring for skin reactions should be performed during treatment. If signs or symptoms indicative of these reactions occur, cefuroxime should be discontinued immediately and alternative therapy should be considered. If a patient develops a serious reaction such as SJS, TEN, or DRESS syndrome while receiving cefuroxime, re-administration of cefuroxime to this patient is absolutely contraindicated.

Overgrowth of non-susceptible microorganisms

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

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

Jarisch-Herxheimer reaction

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

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 appropriate instructions for medical use of sodium cefuroxime should be consulted.

Cefuroxime Deva contains methylparaben and propylparaben, which may cause allergic reactions (possibly delayed).

This medicinal product contains 44.5 mg (250 mg) or 89.0 mg (500 mg) of sodium. Caution is advised when administering to patients on a sodium-restricted diet.

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 and fetal development, delivery, or postnatal development of the offspring. The drug should be prescribed to pregnant women only when the expected benefit outweighs the potential risks.

Breastfeeding period

Cefuroxime passes into breast milk in small amounts. When therapeutic doses are used, adverse reactions are not expected, but the risk of developing diarrhea or fungal mucosal infections in the infant cannot be excluded. Therefore, discontinuation of breastfeeding may be required due to these reactions. The possible sensitizing effect of the drug should also be considered. Cefuroxime may be used during breastfeeding only after the 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 or operating machinery.

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

Dosage and Administration.

Sensitivity to antibiotics may vary over time and by region. When necessary, local antibiotic sensitivity data should be consulted.

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

To ensure optimal absorption, the drug should be taken after meals.

Dosage for adults and children depending on the type of infection is given in Tables 1 and 2.

*apply at the appropriate dosage.

Cefuroxime Deva tablets must not be split and therefore should not be prescribed to patients who are unable to swallow them. In children, the use of the suspension formulation is recommended.

Cefuroxime axetil tablets and cefuroxime axetil granules for the preparation of suspension are not bioequivalent; therefore, these dosage forms are not interchangeable when converted to milligrams.

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

Sequential therapy

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

The duration of both parenteral and oral treatment should be determined based on 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).

*apply in appropriate dosage.

Patients with hepatic impairment

There are no data on the use of this medicinal product in patients with impaired liver function. Since cefuroxime is predominantly excreted by the kidneys, existing liver function disorders are not expected to affect the pharmacokinetics of cefuroxime.

Elderly patients

No special precautions are required for this patient group. Administer usual doses, up to a maximum of 1 g per day.

Children.

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

Cefuroxime Deva tablets cannot be divided and therefore should not be administered to patients unable to swallow the tablet whole.

In children, the drug is recommended to be administered in the form of a suspension.

Overdose.

Neurological complications, including encephalopathy, seizures, and coma, may occur in cases of cephalosporin overdose. Symptoms of overdose may arise if the drug dose has not been appropriately adjusted in patients with renal impairment (see sections "Dosage and administration" and "Special warnings and precautions for use"). Serum cefuroxime levels can be reduced by hemodialysis and peritoneal dialysis.

Adverse Reactions

Adverse effects associated with the use of cefuroxime axetil are generally moderate in severity and mostly reversible.

The adverse reactions listed below are classified by organ systems and frequency of occurrence. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), and not known (frequency cannot be estimated due to insufficient 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 to the surface of erythrocyte membranes and interact with antibodies, potentially leading to a positive Coombs test (which may interfere with blood compatibility testing) and, very rarely, hemolytic anemia.

Cardiac disorders:
Not known – Kounis syndrome.

Immune system disorders:
Hypersensitivity reactions, including:
Uncommon – skin rash;
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 for use").

Hepatobiliary disorders:
Common – transient elevation of 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 (exudative erythema);
Not known – angioneurotic edema, drug-induced eosinophilia with systemic symptoms (DRESS syndrome).

Children.

The safety profile of cefuroxime in pediatric patients is consistent with that observed in adults.

Reporting suspected adverse reactions after drug authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 4 years.

Storage conditions.

Store at temperatures not exceeding 25 °C. Protect from moisture.

Keep out of reach and sight of children.

Packaging.

10 film-coated tablets in a blister; 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Deva Holding A.Ş.

Manufacturer's address and location of operations.

Çerkezköy Organize Sanayi Bölgesi, Karaağaç Mah. Atatürk Cad. No: 32, Kapaklı / Tekirdağ / Turkey