Axef

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AKSEF® (AKSEF®)

Composition:

Active substance: cefuroxime;

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

Excipients: pregelatinized starch, crospovidone, sodium croscarmellose, sodium lauryl sulfate, magnesium stearate, colloidal anhydrous silicon dioxide, coating Sepifilm LP 770: hypromellose, microcrystalline cellulose, stearic acid, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, film-coated white tablets with a break line on one side and the imprint NOBEL on the other.

Pharmacotherapeutic group.

Antibacterials 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 β-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 in different regions and may change over time, with significant differences possible among individual strains. Local data on antibiotic susceptibility 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 insensitive 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 is observed immediately after food intake. Maximum serum cefuroxime levels are reached approximately 2–3 hours after drug 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 cefuroxime levels decrease as a result of dialysis.

Clinical characteristics.

Indications.

The drug 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. History of severe hypersensitivity reactions (e.g., anaphylactic reactions) to any other type 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 the drug and have the potential to eliminate the enhanced absorption effect observed after food intake.

Like other antibacterial agents, cefuroxime may affect intestinal microflora, leading to reduced reabsorption of estrogens and potentially decreasing the efficacy of combined oral contraceptives.

Since a pseudonegative result may occur in the ferricyanide test, glucose determination in blood and plasma of patients receiving cefuroxime axetil should be performed using glucose oxidase or hexokinase methods. Cefuroxime does not interfere with the alkaline picrate method 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).

Effect on diagnostic tests

Serum cefuroxime levels can be 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

The drug should be prescribed with special caution to patients who have experienced hypersensitivity reactions to penicillins or other beta-lactam antibiotics due to the risk of cross-sensitivity. As with all beta-lactam antimicrobial agents, serious 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.

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 prescribed with caution in patients with a history of mild hypersensitivity reactions to other beta-lactam drugs.

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 reactions, and careful monitoring for skin reactions should be performed during treatment. If signs or symptoms suggestive of these reactions occur, cefuroxime should be discontinued immediately and alternative therapy considered. If a patient develops a serious reaction such as SJS, TEN, or DRESS syndrome during cefuroxime treatment, 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 lead to overgrowth of Candida. Prolonged treatment may also result in overgrowth of other non-susceptible microorganisms (e.g. Enterococci, Clostridium difficile), which may require discontinuation of therapy.

Pseudomembranous colitis has been observed during treatment with broad-spectrum antibiotics and may range in severity from mild to life-threatening. Therefore, this should be considered if patients develop severe diarrhea during or after antibacterial therapy. If prolonged or pronounced diarrhea occurs, or if the patient experiences severe colicky abdominal pain, treatment should be discontinued immediately and the patient should undergo thorough evaluation.

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction has been observed during treatment of Lyme disease with cefuroxime axetil. This reaction occurs as a direct result of the bactericidal effect of cefuroxime axetil on Borrelia burgdorferi, the spirochete causing Lyme disease. Patients should be informed that this is a common consequence of antibiotic therapy for Lyme disease and resolves without treatment.

When switching from parenteral to oral therapy, the timing of transition 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 Summary of Product Characteristics for sodium cefuroxime should be consulted.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of cefuroxime in pregnant women are limited. Studies in animals have shown no adverse effects of cefuroxime axetil on pregnancy, embryonic and 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 developing diarrhea or fungal mucosal infections cannot be excluded. Therefore, breastfeeding may need to be discontinued due to these reactions. The possible 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 sodium cefuroxime on fertility in humans. Studies on reproductive function in animals have not shown any effect of this drug on fertility.

Ability to affect the ability to drive or operate machinery.

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

Method of administration and dosage.

Sensitivity to the antibiotic varies depending on the region and may change over time. 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 for adults and children according to the type of infection is provided in Tables 1 and 2.

Adults and children (≥40 kg) Table 1.

Children (<40 kg) Table 2.

Children are recommended to be prescribed the suspension formulation of the drug.

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

The drug is effective for sequential treatment of acute exacerbations of chronic bronchitis following prior parenteral administration of cefuroxime sodium.

Sequential therapy

Acute exacerbations of chronic bronchitis: 750 mg of the drug in injectable form administered 2–3 times daily (intravenously or intramuscularly) for 48–72 hours, followed by oral administration of the drug in tablet form, 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).

Recommended doses of the drug in renal impairment Table 3.

Patients with hepatic impairment

There is no data on the use of this medicinal product in patients with impaired liver function. Cefuroxime is primarily eliminated by the kidneys; therefore, existing liver function disorders are not expected to affect the pharmacokinetics of cefuroxime.

Geriatric patients

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

Children.

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

Axeff® tablets are not recommended for children under 3 years of age.

Children should be prescribed the drug in the form of a suspension.

Overdose.

In case of cephalosporin overdose, central nervous system irritation and neurological complications may occur, including encephalopathy, seizures, and coma. Symptoms of overdose may arise if the drug dose has not been appropriately adjusted in patients with renal impairment.

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.

The adverse reactions listed below are classified by system organ class and frequency of occurrence. Frequencies are defined 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).

Infections and infestations

Common: overgrowth of Candida.

Not known: overgrowth of Clostridium difficile.

Cardiac disorders

Not known: Kounis syndrome.

Blood and lymphatic system disorders

Common: eosinophilia.

Uncommon: positive Coombs test, thrombocytopenia, leukopenia (sometimes severe).

Very rare: hemolytic anemia.

Cephalosporins as a class may adsorb to 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: diarrhea, nausea, abdominal pain.

Uncommon: vomiting.

Rare: pseudomembranous colitis (see section "Special precautions").

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-induced eosinophilia with systemic symptoms (DRESS syndrome).

Children

The safety profile of cefuroxime in children is consistent with that observed in adult patients.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Packaging.

10 tablets in a blister pack.

1 or 2 blister packs in a cardboard box.

Prescription category.

Prescription only.

Manufacturer.

NOBEL ILAC SANAYI VE TICARET A.S.

Manufacturer's address and place of business.

Sancaklar Quarter, Eskisehir Yolu Akcakoca Road No: 299, 81100 Duzce, Turkey.