Cefpotech® 200

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEFOTEK® 200

Composition:

Active substance: cefpodoxime;

1 tablet contains: cefpodoxime proxetil equivalent to cefpodoxime 200 mg;

Excipients: mixture of microcrystalline cellulose and sodium carboxymethylcellulose, sodium lauryl sulfate, hydroxypropylcellulose, colloidal anhydrous silicon dioxide, magnesium stearate, coating Sepifilm LP761 Blanс: 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.

Pharmacotherapeutic group. Antibacterial agents for systemic use. Third-generation cephalosporins. ATC code J01D D13.

Pharmacological properties.

Pharmacodynamics.

Cefpodoxime® 200 is a third-generation oral β-lactam antibiotic. Its bactericidal effect is due to inhibition of bacterial cell wall synthesis in microorganisms. The drug is active against many Gram-positive, Gram-negative, aerobic, and anaerobic microorganisms.

The antimicrobial spectrum of the drug 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 β-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, both penicillinase-producing and non-producing strains (S. aureus and S. epidermidis).

Bacteria resistant to cefpodoxime, 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 ingredient of the drug is absorbed in the small intestine and hydrolyzed to the active metabolite cefpodoxime. Maximum plasma concentration (Cmax) is achieved within 2–4 hours after a single dose administration. Cefpodoxime binds to plasma proteins (mainly albumins) in a non-saturable manner. The minimum inhibitory concentration (MIC) of cefpodoxime against most pathogens is observed in lung parenchyma, bronchial mucosa, pleural fluid, tonsils, interstitial fluid, and prostatic secretion.

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

Clinical characteristics.

Indications.

Infections caused by microorganisms sensitive to cefpodoxime:

• Otorhinolaryngological infections (including sinusitis, tonsillitis, pharyngitis); for the treatment of tonsillitis and pharyngitis, Cefpotek® 200 is indicated in cases of chronic or recurrent infection, as well as when resistance of the causative agent to commonly used antibiotics is known or suspected;
• respiratory tract infections (including acute bronchitis, recurrent or exacerbations of chronic bronchitis, bacterial pneumonia);
• uncomplicated infections of the upper and lower urinary tract (including acute pyelonephritis and cystitis);
• skin and soft tissue infections (abscesses, cellulitis, infected wounds, furuncles, folliculitis, paronychia, carbuncles, and ulcers);
• uncomplicated gonococcal urethritis.

Contraindications.

Hypersensitivity to cephalosporin antibiotics, penicillins, or to any other components of the drug.

Interaction with other medicinal products and other forms of interaction.

Concomitant administration of high doses of antacid agents (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.

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

Administration of cephalosporins may in some cases lead to a positive Coombs' test reaction (see section "Special precautions").

Bioavailability of the drug is reduced by approximately 30% when co-administered with agents that neutralize gastric pH or inhibit gastric secretion.

Cefpodoxime should be taken 2–3 hours after ranitidine administration.

The bioavailability of Cefpotek® 200 increases when the drug is taken with food.

When testing for glucosuria using copper reduction methods (Benedict's or Fehling's), a false-positive reaction may occur; however, cefpodoxime does not interfere with enzymatic methods for glucose detection in urine.

Concomitant use of the drug with loop diuretics may increase nephrotoxicity. Careful monitoring of renal function is recommended when Cefpotek® 200 is administered simultaneously with other nephrotoxic agents.

Plasma levels of cefpodoxime increase when the drug is administered concomitantly with probenecid.

Special precautions for use.

Cross-reactivity between penicillins and cephalosporins has been observed in approximately 5–10% of patients with penicillin allergy. Therefore, prior to prescribing cephalosporins, it is essential to determine whether the patient has a history of penicillin allergy and to ensure strict medical supervision from the first day of cefpodoxime administration. If signs of anaphylactic reaction occur, the drug must be discontinued immediately.

Cefpodoxime is not recommended for patients with known hypersensitivity to cephalosporin antibiotics. Allergic reactions (particularly anaphylaxis) associated with the use of β-lactam antibiotics may be severe and, in rare cases, fatal.

At the first signs of an allergic reaction during treatment with this medicinal product, administration must be stopped immediately and medical advice should be sought.

Cefpodoxime is not an antibiotic suitable for the treatment of staphylococcal pneumonia and should not be used for the treatment of atypical pneumonia caused by Legionella, Mycoplasma, and Chlamydia microorganisms.

Gastrointestinal adverse reactions, including nausea, vomiting, and abdominal pain, may occur during treatment. Therefore, cefpodoxime should be administered with caution to patients with a history of gastrointestinal disorders, particularly colitis. The use of cefpodoxime may lead to the development of diarrhea, antibiotic-associated colitis, and pseudomembranous colitis. These adverse effects, which are more likely to occur in patients receiving high doses of cefpodoxime for prolonged periods, should be considered potentially serious. Testing for Clostridium difficile should be performed. If colitis develops, cefpodoxime therapy must be discontinued immediately, rectosigmoidoscopy should be performed, and appropriate treatment (e.g., vancomycin) should be initiated if further therapy is required. Constipating foods should be avoided. Although any antibiotic may cause pseudomembranous colitis, the risk may be higher with broad-spectrum agents such as cephalosporins.

Neutropenia and agranulocytosis may occur during treatment with β-lactam antibiotics, particularly with prolonged therapy. If treatment duration exceeds 10 days, blood counts should be monitored, and cefpodoxime therapy should be discontinued if neutropenia develops.

Positive Coombs' test reactions may occur during cefpodoxime treatment, and hemolytic anemia is very rare. Cross-resistance between cephalosporins and penicillins may occur with these reactions.

Renal function alterations have been observed when cefpodoxime is used concomitantly with aminoglycosides or potent diuretics; in such cases, monitoring of renal function is required.

Prolonged use of cefpodoxime may result in overgrowth of non-susceptible microorganisms. If superinfection occurs, the patient's condition should be reassessed and appropriate therapy initiated.

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with an incidence of "unknown" in association with cefpodoxime therapy.

Patients should be informed about the signs and symptoms of these reactions and closely monitored for cutaneous reactions.

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

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

Use during pregnancy or breastfeeding.

Data on the safety of cefpodoxime use during pregnancy are lacking. Therefore, during pregnancy, the drug should be used only if the expected benefit to the mother outweighs the potential risk to the fetus, particularly during the first trimester.

Cefpodoxime is excreted in breast milk. If treatment is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

Dizziness may occur during treatment with cefpodoxime, which may impair the ability to drive or operate complex machinery.

Method of administration and dosage.

Tablets should be taken orally during meals to enhance absorption.

For adults and children aged 12 years and older with normal kidney function, the recommended doses are:

The duration of treatment depends on the severity of the disease and is determined individually.

Elderly patients

There is no need to adjust the dose in elderly patients with normal renal function.

Hepatic impairment

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

Renal impairment

There is no need to adjust the dose of Cefpoteck® 200 when creatinine clearance is > 40 mL/min.

If creatinine clearance is below 40 mL/min, the elimination half-life and Cmax increase, therefore the dose of the drug should be adjusted.

* Single dose – 100 mg or 200 mg depending on the type of infection.

Children.

The drug is prescribed to children aged 12 years and older.

Overdose.

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

Treatment. Hemodialysis, peritoneal dialysis. Symptomatic therapy.

Adverse Reactions

General disorders: fungal infections, malaise, increased fatigue, asthenia, fever, chest pain (pain may radiate to the back), back pain, chills, generalized pain, abscess, allergic reactions, facial swelling, bacterial infections, localized swelling, localized pain, growth of insensitive microorganisms.

Cardiovascular system: congestive heart failure, migraine, palpitations, vasodilation, hematomas, arterial hypertension or hypotension.

Gastrointestinal system: diarrhea, abdominal pain, bloating, nausea, tenesmus, abdominal distension, vomiting, dyspepsia, decreased appetite, constipation, anorexia, candidal stomatitis, toothache, belching, gastritis, dry mouth, thirst, oral ulcers, pseudomembranous colitis.

Diarrhea with blood may be a symptom of enterocolitis. In case of severe or persistent diarrhea occurring during or after treatment, pseudomembranous colitis should be suspected (see section "Special precautions for use").

Blood system: hemolytic anemia, decreased hemoglobin, decreased hematocrit, eosinophilia, leukocytosis, leukopenia, lymphocytosis, lymphopenia, agranulocytosis, thrombocytosis, neutropenia, thrombocytopenia, positive Coombs test, prolonged thrombin and prothrombin time.

Metabolic disorders: dehydration, gout, peripheral edema, weight gain.

Musculoskeletal system: myalgia.

Nervous system: headache, vertigo, dizziness, unsteady gait, headache, hemorrhages, anxiety, nervousness, neurosis, insomnia, sleep disturbances, dream abnormalities (unusual dreams, nightmares), paresthesia, confusion.

Respiratory system: bronchial asthma, cough, epistaxis, rhinitis, wheezing, sneezing, bronchospasm, dyspnea, pleural effusion, pneumonia.

Skin: rash, skin hyperemia, urticaria, pruritus, increased sweating, maculopapular and vesiculobullous rashes, fungal dermatitis, epithelial desquamation, dry skin, hair loss, sunburn, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS).

Sensory organs: taste alteration or loss, eye irritation, tinnitus.

Immune system: hypersensitivity reactions of all severity grades have been reported (see section "Special precautions for use"), anaphylactic reactions, angioneurotic edema, purpura, serum sickness, arthralgia, fever.

Urinary and reproductive system: hematuria, urinary tract infections, metrorrhagia, vaginal candidiasis, dysuria, frequent urination, proteinuria, increased urea and creatinine in urine; in isolated cases, renal function disturbances were observed, particularly when cefpodoxime was used concomitantly with aminoglycosides and/or potent diuretics.

Laboratory findings: increased liver function tests (AST, ALT), alkaline phosphatase, bilirubin, urea and creatinine levels; pseudopositive Coombs test.

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

Shelf life. 2 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

5 tablets in a blister; 2 or 4 blisters in a cardboard package.

7 tablets in a blister; 2 blisters in a cardboard package.

Prescription status. Prescription only.

Manufacturer.

NOBEL ILAC SANAYI VE TICARET A.S.

Manufacturer's address and place of business.

Sankaklar Quarter, Eski Akcakoca Avenue, No. 299, 81100 Duzce, Turkey.