Cefodox

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Cefodox (Cefodox)

Composition:

Active substance: cefpodoxime;

5 ml of suspension contain cefpodoxime (as proxetil) 50 mg or 100 mg;

Excipients: hydroxypropylcellulose; microcrystalline cellulose; corn starch; sucrose; citric acid, monohydrate; colloidal anhydrous silicon dioxide; simethicone; sodium carboxymethylcellulose - microcrystalline cellulose; xanthan gum; sodium saccharin; lemon flavor (powder); vanilla flavor (powder).

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties: cream-white powder with lemon flavor.

Pharmacotherapeutic group.

Antibacterials for systemic use. Other beta-lactam antibiotics. Third-generation cephalosporins. ATC code J01DD13.

Pharmacological properties.

Pharmacodynamics.

Cefodox (cefepodoxime in the form of proxetil) is a third-generation beta-lactam antibiotic for oral administration. Its bactericidal effect is due to inhibition of the synthesis of bacterial cell wall components in microorganisms. The drug is active against many Gram-positive, Gram-negative, aerobic and anaerobic microorganisms.

The spectrum of cefepodoxime activity includes the following microorganisms:

Susceptible Gram-positive bacteria – Streptococcus pneumoniae, group A streptococci (S. pyogenes), group B (S. agalactiae), groups C, F and G, as well as S. mitis, S. sanguis, S. salivarius, and Corynebacterium diphtheriae;

Susceptible Gram-negative bacteria – Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis (both beta-lactamase-producing and non-producing strains), Neisseria meningitidis, Neisseria gonorrhoeae, Escherichia coli, Klebsiella spp. (K. pneumoniae; K. oxytoca), Proteus mirabilis;

Moderately susceptible bacteria – methicillin-susceptible staphylococci, strains producing and not producing penicillinase (S. aureus and S. epidermidis).

Bacteria resistant to cefepodoxime, as well as to other cephalosporins, include: enterococci, methicillin-resistant staphylococci (S. aureus and S. epidermidis), Staphylococcus saprophyticus, Pseudomonas aeruginosa and Pseudomonas spp., Clostridium difficile, Bacteroides fragilis.

Pharmacokinetics.

The active substance of the drug is absorbed in the small intestine and hydrolyzed to the active metabolite cefepodoxime. Peak plasma concentrations are achieved within 2–4 hours after a single dose administration. Cefepodoxime binds to plasma proteins (mainly to albumins), with binding following a non-saturable type. The minimum inhibitory concentration (MIC) of cefepodoxime against most pathogens is observed in lung parenchyma, bronchial mucosa, pleural fluid, tonsils, interstitial fluid, and prostatic gland secretion.

It penetrates well into kidney tissues. Within 12 hours after a single dose administration, MIC90 against most pathogens causing kidney and urinary tract infections is achieved. The drug is primarily excreted in urine, with a half-life of approximately 2.4 hours.

Clinical Characteristics.

Indications.

Infections caused by pathogens sensitive to cefpodoxime:

• Infections of the ear, nose, and throat (including acute otitis media, sinusitis, tonsillitis, pharyngitis); Cefodox should be prescribed for the treatment of chronic or recurrent infections, as well as in cases of known or suspected resistance of the pathogen to commonly used antibiotics;
• Respiratory tract infections (including pneumonia, acute bronchitis or bronchiolitis complicated by bacterial superinfection);
• Uncomplicated infections of the upper and lower urinary tracts (including acute pyelonephritis and cystitis);
• Skin and soft tissue infections (abscesses, cellulitis, infected wounds, furuncles, folliculitis, paronychia, carbuncles, and ulcers).

Contraindications.

Hypersensitivity to cephalosporin drugs, penicillins, or any component of the medicinal product. History of immediate-type or severe hypersensitivity reactions to penicillin or any other type of beta-lactam agents. Hereditary fructose intolerance or sucrase-isomaltase deficiency.

Interaction with other medicinal products and other forms of interaction.

Concomitant administration of high doses of antacids (sodium bicarbonate and aluminum hydroxide) or histamine H2-receptor blockers reduces the extent of absorption by 27–32% and Cmax by 24–42%. Oral anticholinesterase agents increase Tmax by 47% but do not affect the extent of absorption. If co-administration with ranitidine is necessary, the drug should be taken 2–3 hours after ranitidine administration.

Cephalosporins may potentially enhance the anticoagulant effect of coumarins and reduce the efficacy of estrogens.

The bioavailability of cefpodoxime increases when administered with food.

When testing urine glucose using copper reduction methods (with Benedict's or Fehling's solutions), false-positive results may occur; however, this does not affect the determination of urine glucose by enzymatic methods.

Concomitant use of the drug with loop diuretics may increase nephrotoxicity. Careful monitoring of renal function is recommended if Cefodox is administered simultaneously with agents exhibiting nephrotoxic effects. Plasma levels of cefpodoxime are increased when the drug is administered with probenecid.

Special precautions for use.

Hypersensitivity reactions.

Due to the possibility of cross-hypersensitivity, it is necessary to establish whether the patient has a history of severe hypersensitivity reactions to cephalosporin or penicillin antibiotics before initiating therapy. If an allergic reaction to cefpodoxime occurs, the drug should be discontinued. Allergic reactions (especially anaphylaxis) observed during treatment with beta-lactam antibiotics may be severe and, in rare cases, may result in death (see section "Adverse reactions"). If exudative multiform erythema, Stevens-Johnson syndrome, or Lyell's syndrome develops, administration of the medicinal product must be discontinued.

Severe skin adverse reactions (SSARs).

Severe skin adverse reactions (SSARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported in association with cefpodoxime therapy, which may be life-threatening or lead to fatal outcomes.

Patients should be informed about the signs and symptoms of SSARs, and careful monitoring for skin reactions is required.

If signs or symptoms suggesting these reactions occur, cefpodoxime should be immediately discontinued and alternative therapy considered.

If a serious reaction such as SJS, TEN, DRESS, or AGEP develops during cefpodoxime treatment, re-administration of cefpodoxime is contraindicated under all circumstances.

Antibacterial activity spectrum.

Cefpodoxime is not the drug of choice for the treatment of staphylococcal pneumonia and should not be used in the treatment of atypical pneumonia caused by Legionella, Mycoplasma, or Chlamydia bacteria.

Effect on renal function.

Dosage regimen should be adjusted in patients with renal impairment according to creatinine clearance values (recommended doses are shown in Table 1). Concomitant use of Cefpodoxime with aminoglycosides or potent diuretics may lead to deterioration of renal function. Monitoring of renal function parameters is recommended during treatment.

Colitis/overgrowth of resistant microorganisms.

Gastrointestinal adverse reactions (e.g., vomiting, nausea, abdominal pain) may occur. Antibiotics should always be administered with caution in patients with gastrointestinal disorders, particularly those with colitis.

Treatment with cefpodoxime and other broad-spectrum antibiotics may disrupt the intestinal microflora balance, leading to diarrhea, colitis, including pseudomembranous colitis caused by Clostridium difficile toxin. These adverse reactions, which are more likely to occur in patients receiving high doses of cefpodoxime for prolonged periods, should be considered potentially severe.

Testing for Clostridium difficile should be performed. If colitis is suspected, the medicinal product should be discontinued immediately, diagnosis confirmed by sigmoidoscopy and/or rectoscopy, and, if clinically indicated, an alternative antibiotic (e.g., vancomycin) should be prescribed. Medicinal products that cause fecal retention should be avoided.

Prolonged use of cefpodoxime may lead to overgrowth of resistant microorganisms, including disruption of normal intestinal flora, resulting in overgrowth of Candida and development of oral mucosal candidiasis (see section "Adverse reactions"). In case of superinfections, the patient's condition should be evaluated and appropriate treatment initiated.

Effect on blood system.

Neutropenia and agranulocytosis may occur during treatment with beta-lactam antibiotics, particularly with prolonged use. If neutropenia develops, treatment with the medicinal product Cefpodoxime should be discontinued.

Effect on serological test results.

The Coombs test may yield false-positive results during cefpodoxime use. A decrease in hemoglobin levels may also occur; hemolytic anemia is possible, although very rare.

Use during pregnancy or breastfeeding.

The medicinal product is intended for use in children.

Ability to influence reaction rate when driving or operating machinery.

The medicinal product is intended for use in children.

Method of administration and dosage.

Cefodox suspension is intended for use in pediatrics. The prepared suspension should be taken orally during meals to enhance absorption.

For children aged from 5 months to 12 years, the recommended dose is 10 mg/kg body weight per day (maximum daily dose – 400 mg), administered in two doses every 12 hours (maximum single dose – 200 mg). The duration of treatment depends on the severity of the disease and is determined individually.

Hepatic impairment.

There is no need to adjust the dose in children with hepatic insufficiency.

Renal impairment.

There is no need to adjust the dose of Cefodox if creatinine clearance is ˃ 40 mL/min.

If creatinine clearance is below 40 mL/min, pharmacokinetic studies indicate an increased elimination half-life and maximum plasma concentration; therefore, the dose of the drug should be adjusted accordingly.

Table 1

For patients undergoing hemodialysis, a single dose calculated according to body weight should be administered after each dialysis session.

Preparation of the suspension

To prepare the suspension, turn the bottle upside down and shake vigorously to loosen the powder. Add boiled water cooled to room temperature in two portions up to the line (mark) on the bottle, shaking vigorously each time until a homogeneous suspension is formed. The volume of the final suspension should reach the line (mark) on the bottle. The suspension may be taken no earlier than 5 minutes after preparation. The prepared suspension must be shaken well before each administration. After preparation, the suspension should be stored for no longer than 14 days in a refrigerator.

A measuring spoon is provided for accurate dosing of the suspension.

Children.

The medicinal product is prescribed to children aged from 5 months to 12 years.

Overdose.

Symptoms: nausea, vomiting, abdominal pain, diarrhea. In cases of overdose, especially in patients with renal insufficiency, encephalopathy may occur. Episodes of encephalopathy are usually reversible with low plasma levels of cefpodoxime.

Treatment: hemodialysis, peritoneal dialysis. Symptomatic therapy.

Adverse Reactions

The following classification of adverse reaction frequencies is used: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).

Infections and infestations: rare – superinfection caused by some Candida species resistant to cefpodoxime; very rare – antibiotic-associated colitis.

Blood and lymphatic system disorders: rare – eosinophilia; very rare – leukopenia, hemorrhage, neutropenia, thrombocytopenia, thrombocytosis, agranulocytosis, serum sickness, decreased hematocrit, decreased hemoglobin concentration, hemolytic anemia, prolonged prothrombin and thrombin time, leukocytosis, lymphopenia, lymphocytosis.

Immune system disorders: rare – hypersensitivity, anaphylactic reactions, angioedema.

Metabolism and nutrition disorders: rare – dehydration, gout, peripheral edema, weight gain.

Musculoskeletal and connective tissue disorders: rare – myalgia, arthralgia.

Nervous system disorders: uncommon – headache; rare – vertigo; very rare – dizziness, gait instability, headache, weakness, insomnia, somnolence, sleep disturbance, neurosis, irritability, nervousness, anxiety, unusual dreams, visual disturbances, confusion, night terrors, paresthesia.

Respiratory, thoracic and mediastinal disorders: rare – asthma, bronchitis, cough, epistaxis, sneezing, rhinitis, wheezing, dyspnea, bronchospasm, sinusitis, pleural effusion, pneumonia.

Gastrointestinal disorders: uncommon – abdominal pain, nausea; rare – diarrhea, thirst, tenesmus, bloating, vomiting, dyspepsia, dry mouth, decreased appetite, sensation of pressure/fullness in stomach, constipation, candidiasis of the mouth, toothache, anorexia, belching, gastritis, mouth ulcers, pseudomembranous colitis.

Hepatobiliary disorders: rare – cholestatic liver injury, increased levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin.

Skin and subcutaneous tissue disorders: rare – rash, erythema, pruritus, urticaria, increased sweating, macular rash, fungal dermatitis, desquamation, dry skin, hair loss, vesicular rash, sunburn erythema, purpura, bullous reactions (including Stevens-Johnson syndrome), toxic epidermal necrolysis, erythema multiforme; frequency not known – acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS).

Renal and urinary disorders: rare – hematuria, urinary tract infections, metrorrhagia, dysuria, frequent urination, nocturia, infections of male genital organs, proteinuria, vaginal pain, vaginal candidiasis. Renal function impairment has been observed in isolated cases.

Cardiac disorders: rare – congestive heart failure, tachycardia, vasodilation, hematoma, migraine, arterial hypertension or hypotension.

Eye disorders: eye irritation.

Ear and labyrinth disorders: tinnitus.

General disorders: rare – discomfort, increased fatigue, asthenia, chills, drug fever, chest pain (pain may radiate to the back), fever, generalized pain, localized swelling, localized pain, taste disturbances, abscess, allergic reaction, facial swelling, candidiasis, bacterial infections, parasitic infections.

Biochemical tests: hyper- or hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperkalemia, hyponatremia.

Laboratory findings: increased levels of urea and creatinine, false-positive Coombs test.

Reporting suspected adverse reactions after marketing authorization is highly important. Cases of suspected adverse reactions and lack of drug efficacy should be reported to the physician or through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life.

2 years (unopened vial).

After reconstitution, the prepared suspension should be stored for no longer than 14 days in the refrigerator.

Storage conditions.

Store at temperatures not exceeding 30 °C.

Keep out of reach of children.

Packaging.

Dry powder in a vial. 1 vial with dosing spoon in a cardboard box.

Prescription status.

Prescription only.

Manufacturer/Marketing Authorization Holder.

Pharma International Company.

Address of manufacturer and its place of business.

Al Castal area, Airport Road, P.O. Box 334, Jubaiha 11941, Amman – Jordan.

Address of Marketing Authorization Holder.

P.O. Box 334 Al-Jubaiha 11941 Amman, Jordan.

Contact details of the manufacturer's/Marketing Authorization Holder's representative in Ukraine – LLC "MegaCom":

195B Klochkivska Street, Kharkiv, 61145, Ukraine; phone: +38 (057) 701 37 55.