Auroxetil

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AURORXETIL (AUROXETIL)

Composition:

Active substance: cefuroxime axetil;

One film-coated tablet contains cefuroxime axetil (equivalent to cefuroxime) 250 mg or 500 mg;

Excipients: microcrystalline cellulose, sodium croscarmellose, sodium lauryl sulfate, colloidal anhydrous silicon dioxide, hydrogenated vegetable oil, hypromellose, polyethylene glycol, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets, capsule-shaped, from almost white to white in color, marked with embossing "A33" on one side and smooth on the other side for the 250 mg dosage; and film-coated tablets, capsule-shaped, from almost white to white in color, marked with embossing "A34" on one side and smooth on the other side for the 500 mg dosage.

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

Cefuroxime is generally active in vitro against the following microorganisms:

*All methicillin-resistant Staphylococcus 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 concentration of cefuroxime is 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.

Serum levels of cefuroxime are reduced as a result of dialysis.

Clinical characteristics.

Indications.

Auroxetil 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.

The drug should be prescribed in accordance with current official guidelines for the use of antibacterial agents.

Contraindications.

Hypersensitivity to cephalosporin antibiotics, cefuroxime, or to any component of the drug. History of severe hypersensitivity reactions (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 Auroxetil and may abolish the enhanced absorption effect observed after food intake.

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

Since pseudonegative results may occur with the ferricyanide test, it is recommended to use glucose oxidase or hexokinase methods for determining glucose levels in blood and plasma in patients treated with cefuroxime axetil. Cefuroxime does not interfere with the alkaline picrate method for creatinine determination.

Concomitant use with probenecid is not recommended, as it significantly increases the peak concentration, area under the plasma concentration-time curve (AUC), and elimination half-life of cefuroxime.

Concomitant administration with oral anticoagulants may lead to an increased INR (International Normalized Ratio).

Cefuroxime levels in blood serum are reduced by dialysis.

High-dose cefuroxime should be administered with caution in patients receiving potent diuretics, aminoglycosides, or amphotericin, as such combinations increase the risk of nephrotoxicity.

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

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, serious and occasionally 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 medical care should be provided.

Severe cutaneous adverse reactions

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 during cefuroxime treatment (see section "Adverse reactions").

Patients should be informed about the signs and symptoms of such skin reactions, and careful monitoring is required. If signs or symptoms suggestive of these 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 that patient is 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 agents. Cefuroxime should be administered with caution in patients with a history of mild hypersensitivity reactions to other beta-lactam medicinal products.

Administration 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.

Pseudomembranous colitis has been reported during antibiotic use, ranging from mild to life-threatening severity. Therefore, this should be considered if a patient develops severe diarrhea during or after antibacterial therapy. 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. Medicinal products that inhibit peristalsis should not be administered.

Jarisch-Herxheimer reaction has been observed during cefuroxime axetil treatment of Lyme disease, directly due to 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, which resolves without 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. Prior to initiating sequential therapy, the relevant Instructions for Medical Use of cefuroxime sodium 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. Cefuroxime axetil should be administered to pregnant women only when the potential benefit outweighs the possible risks.

Breastfeeding period

Cefuroxime passes into breast milk in small amounts. With therapeutic doses of the medicinal product, adverse reactions are not expected; however, 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 medicinal product 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 did not reveal any effect of this medicinal product on fertility.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration

Sensitivity to antibiotics 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 meals.

Dosage regimens for adults and children depending on the type of infection are presented in Tables 1 and 2.

Table 1

Adults and children (≥ 40 kg)

Table 2

Children (< 40 kg)

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

Auroxetil tablets must not be split; therefore, they are not prescribed to patients who cannot swallow tablets. In children, the medicinal product should be administered in the form of a suspension.

Cefuroxime axetil tablets are not bioequivalent to cefuroxime axetil oral suspension; therefore, these products are not interchangeable on a milligram-per-milligram basis.

Patients with renal impairment

Cefuroxime is primarily eliminated via the kidneys. In patients with marked impairment of renal function, the dose of cefuroxime should be reduced to compensate for its slower excretion (see Table 3).

Table 3

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 existing liver dysfunction 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. Aurorocetil tablets cannot be divided and therefore should not be administered to patients who are unable to swallow tablets. The suspension formulation is recommended for children.

Overdose.

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

Serum cefuroxime concentrations may be reduced by hemodialysis and peritoneal dialysis.

Adverse reactions.

Adverse effects associated with the use of cefuroxime axetil are generally mild and mainly reversible.

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

Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000).

Children.

The safety profile of cefuroxime in children corresponds to that observed in adult patients.

Reporting of suspected adverse reactions. It is important to report suspected adverse reactions following marketing authorization of the medicinal product. This enables continued monitoring of the benefit/risk balance. Please report suspected adverse reactions through the national reporting system.

Shelf life. 3 years.

Storage conditions.

Keep out of the reach and sight of children. Store at temperatures not exceeding 30 °C.

Packaging. 10 tablets per blister, 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer. Aurobindo Pharma Ltd. Unit VI, Block D/Aurobindo Pharma Ltd. Unit V Block D.

Manufacturer's address and place of business.

Sy. No. 329/39 & 329/47, Chitkul Village, Patancheru Mandal, Sanga Reddy District, Telangana state, 502307 India.