Cefuroxime sandoz®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Cefuroxime SANDOZ®

Composition:

Active substance: cefuroxime;

One tablet contains cefuroxime axetil equivalent to 250 mg or 500 mg of cefuroxime;

Excipients: sodium lauryl sulfate, copovidone, sodium croscarmellose, magnesium stearate, colloidal anhydrous silicon dioxide, mannitol (E 421), microcrystalline cellulose, crospovidone, talc;

coating: Opadry YS-1R 7003 White (hypromellose, titanium dioxide (E 171), polyethylene glycol, polysorbate 80).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

250 mg tablets: elongated, biconvex tablets with notches on both sides, white to light yellow in color;

500 mg tablets: elongated, biconvex tablets, white to light yellow in color.

Pharmacotherapeutic group.

Antibacterials for systemic use. 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. When available, local data on antibiotic susceptibility should be consulted, 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 of the latter, and enters the bloodstream as cefuroxime.

Optimal absorption is observed immediately after food intake. Maximum serum cefuroxime concentrations are 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 cefuroxime levels are reduced by dialysis.

Clinical characteristics.

Indications.

Cefuroxime Sandoz® 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 medicinal product. 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 interaction.

Agents that reduce gastric acidity may decrease the bioavailability of cefuroxime and have the potential to eliminate the enhanced absorption effect observed after food intake.

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

Since pseudonegative results may occur with the ferricyanide test, glucose oxidase or hexokinase methods are recommended for determining plasma glucose levels in patients receiving cefuroxime. Cefuroxime does not interfere with 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 result in an increased international normalized ratio (INR).

Serum levels of cefuroxime are reduced by dialysis.

Positive Coombs' test results have been reported during treatment with cephalosporins. This phenomenon may affect cross-matching of blood compatibility.

Special precautions for use.

Hypersensitivity reactions. Particular 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 antimicrobial agents, severe and occasionally fatal hypersensitivity reactions have been reported. Hypersensitivity reactions progressing to Kounis syndrome – acute allergic coronary artery spasm, which may lead to myocardial infarction, have been reported (see section "Adverse reactions"). In case of severe hypersensitivity reactions, cefuroxime therapy should be discontinued immediately and appropriate emergency medical treatment should be administered.

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 therapy (see section "Adverse reactions").

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

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 to patients with a history of mild hypersensitivity reactions to other beta-lactam medicinal products.

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

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

During treatment of Lyme disease, a Jarisch-Herxheimer reaction has been observed, which is directly caused by the bactericidal effect of cefuroxime on the causative organism, the spirochete Borrelia burgdorferi. Patients should be informed that this is a common consequence of antibiotic therapy for Lyme disease and resolves without specific treatment.

In sequential therapy, the timing of transition from parenteral to oral treatment 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 prescribing information for cefuroxime sodium for parenteral use should be consulted.

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. The drug should be administered to pregnant women only when the potential benefit outweighs the possible risks.

Period of breastfeeding. Cefuroxime passes into breast milk in small amounts. When therapeutic doses are used, adverse reactions are not expected, but the risk of diarrhea or fungal mucosal infections in the infant cannot be excluded. Therefore, discontinuation of breastfeeding may be necessary due to these potential reactions. The possible sensitizing effect of the drug should also be considered. Cefuroxime should be used during breastfeeding only after careful assessment by a physician of the benefit-risk ratio.

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 a vehicle or operating machinery.

Method of administration and dosage.

Sensitivity to antibiotics may vary over time and depending on the region. When 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 regimens for adults and children depending on the infection are presented in Tables 1 and 2.

Adults and children (≥ 40 kg): Table 1

Children (< 40 kg) Table 2

Tablets of 250 mg have a score line on both sides and can be divided into equal 125 mg doses.

There is no experience with the use of cefuroxime axetil in children under 3 months of age. The suspension formulation is recommended for children.

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

Cefuroxime axetil is also available as the sodium salt for parenteral administration. This allows for sequential therapy with a single antibiotic when switching from parenteral to oral administration, if there are clinical indications for such a change.

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 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 by 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 is no data on the use of this medicinal product in patients with impaired liver function. Since cefuroxime is primarily eliminated by the kidneys, existing liver dysfunction is not expected to 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. The suspension formulation is recommended for administration to children.

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 impaired renal function. 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 mainly reversible. The adverse reactions listed below are classified by system organ class and frequency of occurrence. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (frequency cannot be estimated due to lack of data).

Cardiac disorders: not known – Kounis syndrome.

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, to 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 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 (exanthematous necrolysis); not known – angioneurotic edema, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

Children.

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

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

7 tablets per blister, 2 blisters (7 × 2) in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Sandoz GmbH – Production Unit Anti-Infectives GMP and Chemical Operations Kundl (AIHO GMP Kundl).

Manufacturer's address and place of business.

Biochemistrasse 10, 6250 Kundl, Austria.