Focerio

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FOKSERO® (FOXERO®)

Composition:

Active substance: cefpodoxime;

1 tablet contains cefpodoxime proxetil equivalent to cefpodoxime 100 mg or 200 mg;

Excipients: lactose monohydrate; magnesium stearate; calcium carmellose; low-substituted hydroxypropylcellulose; sodium lauryl sulfate; Opadry White 03A28718 (hypromellose (E 464); titanium dioxide (E 171); talc).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

100 mg tablets:

white to almost white, round, biconvex, film-coated tablets, with "100" imprinted on one side;

200 mg tablets:

white to almost white, round, biconvex, film-coated tablets, with "200" imprinted on one side.

Pharmacotherapeutic group. Antibacterials for systemic use. Other β-lactam antibiotics. Third-generation cephalosporins. ATC code J01D D13.

Pharmacological properties.

Pharmacodynamics.

Cefpodoxime proxetil is a third-generation oral cephalosporin β-lactam antibiotic and is a prodrug of cefpodoxime.

The mechanism of action of cefpodoxime is due to inhibition of bacterial cell wall synthesis in microorganisms. It is stable against numerous β-lactamases.

In vitro, cefpodoxime exerts a bactericidal effect against many Gram-positive and Gram-negative bacteria.

Cefpodoxime is highly active against Gram-positive microorganisms: Streptococcus pneumoniae; Group A (S. pyogenes), B (S. agalactiae), C, F, and G streptococci; other streptococci (S. mitis, S. sanguis, and S. salivarius); Corynebacterium diphtheriae.

Cefpodoxime is highly active against Gram-negative microorganisms: Haemophilus influenzae (strains producing and not producing β-lactamase); Haemophilus para-influenzae (strains producing and not producing β-lactamase); Branhamella catarrhalis (strains producing and not producing β-lactamase); Neisseria meningitidis; Neisseria gonorrhoeae; Escherichia coli; Klebsiella spp. (K. pneumoniae, K. oxytoca); Proteus mirabilis.

Cefpodoxime shows moderate activity against methicillin-susceptible staphylococci, both penicillinase-producing and non-producing strains (S. aureus and S. epidermidis).

Resistant to cefpodoxime are: enterococci; methicillin-resistant staphylococci (S. aureus and S. epidermidis); Staphylococcus saprophyticus; Pseudomonas aeruginosa and Pseudomonas spp.; Clostridium difficile; Bacteroides fragilis and related species.

If possible, susceptibility should be determined by in vitro testing.

Pharmacokinetics.

Absorption. Cefpodoxime proxetil is absorbed in the intestine and hydrolyzed to its active metabolite, cefpodoxime. After oral administration of cefpodoxime proxetil (tablet containing 100 mg of cefpodoxime) on an empty stomach, drug absorption is 51.1%. Food intake prolongs the absorption period.

Distribution. Volume of distribution is 32.3 L. Maximum plasma concentration of cefpodoxime is reached within 2–3 hours after administration. Maximum plasma concentration is 1.2 mg/L after a 100 mg dose and 2.5 mg/L after a 200 mg dose. After administration at doses of 100 mg and 200 mg twice daily for 14.5 days, pharmacokinetic parameters of cefpodoxime in plasma did not change.

Protein binding to serum proteins is 40%, mainly to albumin. Protein binding is non-saturable.

Cefpodoxime penetrates into lung parenchyma, bronchial mucosa, pleural fluid, tonsils, interstitial fluid, and prostate tissues. Good diffusion of cefpodoxime has also been observed in renal tissue.

It is predominantly excreted in urine, where high concentrations are achieved.

Metabolism. Cefpodoxime proxetil is a prodrug of cefpodoxime. Almost all of the absorbed drug undergoes de-esterification, presystemically in the small intestine, and is converted into its active form. Cefpodoxime undergoes negligible metabolism and is excreted unchanged, primarily in urine.

Excretion. The main route of elimination is via the kidneys; approximately 80% is excreted unchanged in urine. Elimination half-life is approximately 2.4 hours.

Clinical characteristics.

Indications.

Treatment of infections caused by microorganisms sensitive to the drug:

• infections of the ear, nose and throat organs (including sinusitis, tonsillitis, pharyngitis);
• paranasal sinus infections (including sinusitis);
• respiratory tract infections (including acute bronchitis, exacerbation of chronic bronchitis, bacterial pneumonia);
• upper urinary tract infections (including acute uncomplicated pyelonephritis);
• lower urinary tract infections (including acute uncomplicated cystitis);
• skin and soft tissue infections;
• acute uncomplicated gonococcal urethritis.

Contraindications.

Hypersensitivity to cefpodoxime, other cephalosporins, penicillins, or to any component of the drug.

Rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

Interaction with other medicinal products and other types of interactions.

Histamine H2-receptor antagonists and antacids reduce the bioavailability of cefpodoxime. Probenecid reduces the excretion of cephalosporins. Cephalosporins may enhance the anticoagulant effect of coumarins.

Isolated cases of positive Coombs' test have been reported (see section "Special precautions").

Concomitant administration of cefpodoxime with agents that neutralize gastric pH or inhibit gastric acid secretion reduces bioavailability by approximately 30%. Therefore, such agents as mineral-type antacids and H2-blockers, such as ranitidine, which may lead to an increase in gastric pH, should be taken 2–3 hours after administration of cefpodoxime.

Bioavailability increases when the drug is taken with food.

A false-positive reaction for glucose in urine may occur when using Benedict's or Fehling's solutions or copper sulfate; however, such a reaction has not been observed with tests based on enzymatic glucose-oxidase reactions.

Special precautions for use.

Before prescribing cephalosporins, it is necessary to review the patient's history of allergy to penicillins, since cross-allergic reactions to penicillins occur in 5–10% of cases.

For patients with allergic reactions to other cephalosporins, the possibility of cross-allergic reactions to cefpodoxime should be considered. Cefpodoxime should not be administered to patients with a history of immediate-type hypersensitivity reactions to cephalosporins.

Allergic reactions (anaphylaxis) to β-lactam antibiotics can be severe and sometimes even fatal.

If any signs of hypersensitivity occur, treatment should be discontinued immediately.

In cases of severe renal impairment, dose adjustment may be necessary depending on creatinine clearance.

Cefpodoxime is not the first-choice antibiotic for the treatment of staphylococcal pneumonia and therefore should not be used in the treatment of atypical pneumonia caused by microorganisms such as Legionella, Mycoplasma, and Chlamydia.

Possible adverse reactions include gastrointestinal disturbances such as nausea, vomiting, and abdominal pain. Antibiotics should be prescribed with caution to patients with a history of gastrointestinal disorders (particularly colitis).

Cefpodoxime may cause diarrhea, antibiotic-associated colitis, and pseudomembranous colitis. These adverse reactions, which occur more frequently in patients receiving high doses over a prolonged period, should be considered potentially serious.

Testing for C. difficile should be performed. If colitis is suspected, treatment should be discontinued immediately. Diagnosis should be confirmed by sigmoidoscopy and/or rectoscopy, and if clinically indicated, an alternative antibiotic (vancomycin) should be administered. Agents causing fecal retention should be avoided. When using broad-spectrum antibiotics such as cephalosporins, the risk of developing pseudomembranous colitis is increased.

As with other β-lactam antibiotics, neutropenia may develop, and agranulocytosis may occur less frequently, particularly during prolonged therapy. If treatment lasts longer than 10 days, a blood test should be performed, and treatment should be discontinued if neutropenia is detected.

Cephalosporins may adsorb onto the surface of erythrocyte membranes and react with antibodies directed against the drug. They may induce a positive Coombs test and very rarely lead to hemolytic anemia. Such a reaction may result in cross-reactivity with penicillins.

When used concomitantly with potentially nephrotoxic agents such as aminoglycosides and/or potent diuretics (e.g., furosemide), renal function should be monitored.

Prolonged use of cefpodoxime may lead to overgrowth of resistant microorganisms. Oral antibiotics may alter the normal microbial flora of the colon, leading to proliferation of Clostridium and subsequent pseudomembranous colitis. Re-evaluation of the patient is necessary; if superinfection occurs during therapy, appropriate measures should be taken.

One 100 mg tablet contains 9 mg of lactose monohydrate.

One 200 mg tablet contains 18 mg of lactose monohydrate.

Use during pregnancy or breastfeeding.

Focsoro® may be used during pregnancy only if clearly needed.

Cefpodoxime is excreted in breast milk; therefore, if its use is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

Cefpodoxime has generally been shown not to affect the ability to concentrate and react. However, rare adverse reactions such as hypotension or dizziness may occur, which could pose a risk when performing the aforementioned activities (see also section "Adverse reactions").

Dosage and Administration

For oral use. The tablets should be taken with food for optimal absorption.

Adults with normal renal function

Sinusitis: 200 mg twice daily.

Tonsillitis and pharyngitis: 100 mg twice daily.

Acute bronchitis, acute exacerbation of chronic bronchitis, and bacterial pneumonia: 100–200 mg twice daily, depending on the severity of the infection.

Uncomplicated lower urinary tract infections: 100 mg twice daily.

Uncomplicated upper urinary tract infections: 200 mg twice daily.

Skin and soft tissue infections: 200 mg twice daily.

Uncomplicated gonococcal urethritis: 200 mg as a single dose.

Elderly patients

Dose adjustment in elderly patients with normal renal function is not required.

Children

Tablets can be administered to children aged 12 years and older at a dose of 100 mg twice daily. For children under 12 years of age, Focséro**®** oral suspension powder is recommended.

Hepatic impairment

Dose adjustment is not required in patients with hepatic impairment.

Renal impairment

Dose adjustment is not required in patients with renal impairment and a creatinine clearance greater than 40 mL/min/1.73 m². If creatinine clearance is below this value, the dose should be adjusted accordingly (see table).

1The standard dose is 100 mg or 200 mg, depending on the type of infection.

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

Children.

Tablets are indicated for children aged 12 years and older. For children under 12 years of age, Focséro**®** oral suspension powder is recommended.

Overdose.

Symptoms: nausea, vomiting, abdominal pain, diarrhea. In cases of overdose, especially in patients with renal insufficiency, encephalopathy may develop. Encephalopathy is usually reversible and resolves with decreasing plasma levels of cefpodoxime.

Treatment: Hemodialysis, peritoneal dialysis. Supportive and symptomatic therapy.

Side effects

Side effects are classified by system organ class and frequency: very common (>1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

Infections and infestations:

Common – superinfection caused by certain Candida species resistant to cefpodoxime (see section "Special precautions");

Superinfection: as with other antibiotics, the use of cefpodoxime, especially prolonged use, may lead to overgrowth of non-susceptible organisms. Patient condition should be re-evaluated. If superinfection occurs during therapy, appropriate measures should be taken.

Very rare – antibiotic-associated colitis.

Blood and lymphatic system disorders:

Uncommon – thrombocytosis (usually reversible after discontinuation of treatment);

Very rare – anemia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, decreased hemoglobin concentration, hemolytic anemia, eosinophilia, lymphocytosis, leukocytosis.

Immune system disorders:

Rare – hypersensitivity, reactions of all severity grades, from bronchospasm and angioedema to life-threatening shock;

Very rare – anaphylactic reactions.

Metabolic and nutritional disorders:

Rare – dehydration, gout, peripheral edema, weight gain.

Musculoskeletal and connective tissue disorders:

Rare – myalgia.

Nervous system disorders:

Uncommon – headache, dizziness, paresthesia;

Rare – vertigo;

Very rare – insomnia, somnolence, neurosis, irritability, nervousness, unusual dreams, visual disturbances, confusion, night terrors.

Respiratory, thoracic and mediastinal disorders:

Rare – asthma, cough, epistaxis, rhinitis, wheezing, bronchitis, dyspnea, pleural effusion, pneumonia, sinusitis.

Gastrointestinal disorders:

Common – diarrhea, abdominal distension, abdominal pain, nausea, vomiting, decreased appetite;

Rare – thirst, tenesmus, dyspepsia, dry mouth, constipation, candidiasis stomatitis, anorexia, eructation, gastritis, oral ulcers, pseudomembranous colitis, blood in stools, acute pancreatitis.

In case of severe persistent diarrhea during or after completion of treatment, pseudomembranous enterocolitis should be considered (see section "Special precautions").

Hepatobiliary disorders:

Very rare – liver injury, cholestatic liver injury;

Rare – acute hepatitis.

Skin and subcutaneous tissue disorders:

Uncommon – rash, pruritus, urticaria, purpura;

Rare – increased sweating, maculopapular rash, fungal dermatitis, desquamation, dry skin, alopecia, vesicular rash, photosensitivity erythema, bullous reactions (including Stevens-Johnson syndrome), toxic epidermal necrolysis, erythema multiforme.

Renal and urinary disorders:

Rare – acute renal failure, hematuria, urinary tract infections, metrorrhagia, dysuria, increased urinary frequency, proteinuria, vaginal candidiasis.

Changes in renal function have been reported with antibiotics of the same class as cefpodoxime, particularly when used concomitantly with aminoglycosides and/or potent diuretics.

Cardiovascular disorders:

Rare – congestive heart failure, migraine, tachycardia, vasodilation, hematoma, arterial hypertension or hypotension (see section "Special precautions").

Ear and labyrinth disorders:

Uncommon – tinnitus;

Rare – taste disturbances, eye irritation.

General disorders and administration site conditions:

Rare – discomfort, malaise, fatigue, asthenia, drug fever, chest pain (pain may radiate to the back), fever, generalized pain, candidiasis, allergic reaction, facial swelling, bacterial infections, parasitic infections.

Investigations:

Uncommon – bilirubinemia;

Rare – increased levels in liver function tests (AST, ALT), alkaline phosphatase, blood urea, creatinine; pseudopositive Coombs test.

Biochemical tests:

Hyper- or hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperkalemia, hyponatremia.

Shelf life.

2 years. Do not use after the expiry date stated on the packaging.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 film-coated tablets in an aluminum foil blister.

1 or 2 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

ALKALOID AD Skopje.

Address of the manufacturer and location of business operations.

Boulevard Aleksandar Makedonski 12, Skopje, 1000, Republic of North Macedonia.