Cefma pediatric suspension

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEFMACHILD SUSPENSION (CEFMACHILD SUSPENSION)

Composition:

Active substance: cefpodoxime;

5 ml of oral suspension contains 52.219 mg of cefpodoxime proxetil, equivalent to 40 mg of cefpodoxime;

Excipients: silicon dioxide, iron oxide (E 172), talc, sorbitan trioleate, lemon flavor, anhydrous citric acid, sodium chloride, sodium benzoate (E 211), orange flavor, aspartame (E 951), guar gum (E 412), sucrose.

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties: powder – creamy to orange-yellow in color; ready-to-use suspension – orange-yellow in color. The powder and suspension have a fruity or slightly fruity odor.

Pharmacotherapeutic group.

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

Pharmacological Properties

Pharmacodynamics

Cefpodoxime exerts antibacterial activity by binding to and inhibiting specific enzymes involved in bacterial cell wall synthesis—namely penicillin-binding proteins. This leads to interruption of cell wall (peptidoglycan) biosynthesis, resulting in bacterial cell lysis and death.

In vitro, cefpodoxime exhibits bactericidal activity against numerous Gram-positive and Gram-negative bacteria.

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

Cefpodoxime is highly active against the following Gram-negative microorganisms: Haemophilus influenzae (both β-lactamase-producing and non-producing strains); Haemophilus parainfluenzae (both β-lactamase-producing and non-producing strains); Branhamella catarrhalis (both β-lactamase-producing and non-producing strains); Neisseria meningitidis; Neisseria gonorrhoeae; Escherichia coli; Klebsiella spp. (K. pneumoniae, K. oxytoca); Proteus mirabilis.

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

Organisms resistant to cefpodoxime include: Enterococci; methicillin-resistant staphylococci (S. aureus and S. epidermidis); Staphylococcus saprophyticus; Pseudomonas aeruginosa and other Pseudomonas spp.; Clostridium difficile; Bacteroides fragilis and related species.

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

Pharmacokinetics

Cefpodoxime proxetil is absorbed in the gastrointestinal tract and hydrolyzed to its active metabolite, cefpodoxime. Following oral administration of a 100 mg cefpodoxime-equivalent tablet given on an empty stomach, 51.1% is absorbed, and absorption increases when taken with food. The volume of distribution is 32.3 L, and peak plasma levels of cefpodoxime occur 2–3 hours after administration. Maximum plasma concentrations are 1.2 mg/L and 2.5 mg/L after 100 mg and 200 mg doses, respectively. After administration of 100 mg and 200 mg twice daily for 14.5 days, pharmacokinetic parameters of cefpodoxime in plasma remain unchanged. Plasma protein binding of cefpodoxime is 40%, primarily to albumin, and this binding is of a non-saturable type. Concentrations of cefpodoxime exceeding the minimum inhibitory concentrations (MICs) for common pathogenic microorganisms can be achieved in lung parenchyma, bronchial mucosa, pleural fluid, tonsils, interstitial fluid, and prostatic tissue. Studies in healthy volunteers show that median concentrations of cefpodoxime in total ejaculate 6–12 hours after a single 200 mg dose exceed the MIC₉₀ for N. gonorrhoeae. Since most of the cefpodoxime is excreted in urine, concentrations are high (urinary concentrations during 0–4, 4–8, and 8–12 hour intervals after a single dose exceed the MIC₉₀ for common urinary pathogens). Good penetration of cefpodoxime into renal tissue is also observed, with concentrations exceeding the MIC₉₀ for common urinary pathogens 3–12 hours after a single 200 mg dose (1.6–3.1 μg/g). Cefpodoxime concentrations in brain tissue and cerebral cortex are similar. The primary route of elimination is renal, with approximately 80% excreted unchanged in urine and a half-life of approximately 2.4 hours.

Children

Studies in children have shown that maximum plasma concentrations occur approximately 2–4 hours after dosing. A single dose of 5 mg/kg in children aged 4–12 years results in plasma concentrations similar to those observed in adults receiving a 200 mg dose.

In patients under 2 years of age receiving multiple doses of 5 mg/kg every 12 hours, mean plasma concentrations 2 hours after dosing range from 2.7 mg/L (1–6 months) to 2.0 mg/L (7 months–2 years).

In patients aged 1 month to 12 years receiving multiple doses of 5 mg/kg every 12 hours, trough plasma concentrations at steady state range from 0.2–0.3 mg/L (1 month–2 years) to 0.1 mg/L (2–12 years).

Clinical characteristics.

Indications.

Treatment of infections caused by pathogens sensitive to the drug:

• infections of the ear, nose and throat organs (including sinusitis, tonsillitis, pharyngitis, acute and middle otitis);
• respiratory tract infections (including pneumonia, bronchopneumonia, acute exacerbation of chronic bronchitis);
• uncomplicated infections of the upper and lower urinary tracts;
• skin and soft tissue infections.

Contraindications.

Hypersensitivity to cefpodoxime, cephalosporin group drugs, or to any component of the medicinal product.

Immediate-type or severe hypersensitivity reactions in history to penicillin or any other type of beta-lactam drugs.

Since the medicinal product contains aspartame, it should not be administered to children suffering from phenylketonuria.

For neonates under 28 days of age and infants from 4 weeks to 3 months of age with renal insufficiency, treatment with the drug is not recommended due to lack of experience.

Interaction with other medicinal products and other types of interactions.

H₂-histamine receptor antagonists and antacid agents reduce the bioavailability of cefpodoxime. Probenecid reduces the excretion of cephalosporins. Cephalosporins may potentiate the anticoagulant effect of coumarins and reduce the contraceptive effect of estrogens.

Isolated cases of positive Coombs test have been reported.

Studies have shown that bioavailability decreases by approximately 30% when cefpodoxime is administered simultaneously with agents that neutralize gastric pH or inhibit acid secretion. Therefore, such agents as mineral-type antacids and H₂-blockers, which may lead to increased gastric pH, should be taken 2–3 hours after administration of cefpodoxime.

Bioavailability increases when the drug is taken with food.

Cefpodoxime should not be used concomitantly with bacteriostatic antibiotics (e.g., chloramphenicol, erythromycin, sulfonamides, or tetracyclines), as the effect of cefpodoxime may be reduced.

A pseudopositive 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 starting therapy, it is necessary to determine whether the patient has had any hypersensitivity reactions to cefpodoxime, cephalosporins, penicillins, or other beta-lactam antibiotics in the past.

This medicinal product is contraindicated in patients with a history of immediate-type or severe hypersensitivity reactions to penicillin or other beta-lactam agents. Allergic reactions (anaphylaxis) to beta-lactam antibiotics can be serious and sometimes even fatal.

Patients with any other type of allergic reaction (e.g., hay fever or bronchial asthma) should also use cefpodoxime with special caution, as the risk of severe hypersensitivity reactions is increased in such cases.

In the case of severe acute hypersensitivity reactions, treatment with the drug should be discontinued immediately and appropriate emergency measures should be initiated without delay.

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

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 microorganisms such as Legionella, Mycoplasma, and Chlamydia.

Prolonged or repeated use of the medicinal product may lead to superinfection or colonization by resistant microorganisms or blastomycetes (e.g., candidiasis, vaginitis).

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

Administration of the drug is not recommended in cases of severe gastrointestinal disturbances accompanied by vomiting and diarrhea, as adequate absorption from the gastrointestinal tract cannot be ensured.

Antibiotic-associated diarrhea, colitis, and pseudomembranous colitis have been observed during cefpodoxime use. These diagnoses should be considered in any patient who develops diarrhea during or shortly after initiation of therapy. Cefpodoxime therapy should be discontinued in the event of severe and/or bloody diarrhea, and appropriate treatment should be initiated. Cefpodoxime should always be used with caution in patients with gastrointestinal disorders, especially colitis.

Testing for C. difficile should be performed. In case of suspected enterocolitis, treatment should be discontinued immediately. Diagnosis should be 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 and inhibit peristalsis should be avoided. When using broad-spectrum agents such as cephalosporins, there is an increased risk of developing pseudomembranous colitis.

As with all beta-lactam antibiotics, neutropenia and, more rarely, agranulocytosis may develop, especially during prolonged therapy. If treatment lasts longer than 10 days, blood counts should be monitored, and therapy should be discontinued if neutropenia is detected.

Cephalosporins may adsorb onto the surface of erythrocyte membranes and react with antibodies produced against the drug. This may result in a positive Coombs test and, very rarely, hemolytic anemia. Cross-reactivity with penicillin may occur in this reaction.

The Coombs test and non-enzymatic methods for measuring glucose in urine may yield false-positive results during treatment with cephalosporins.

Changes in renal function have been observed with cephalosporin antibiotics, particularly when administered concomitantly with potentially nephrotoxic agents such as aminoglycosides and/or potent diuretics (e.g., furosemide). In such cases, renal function should be monitored.

Dose adjustment is not required if creatinine clearance exceeds 40 ml/min. For patients with creatinine clearance less than 40 ml/min and for those undergoing hemodialysis, the dosing interval should be extended.

If exudative multiform erythema, Stevens-Johnson syndrome, or Lyell's syndrome occurs, the drug should be discontinued immediately.

As with other antibiotics, prolonged use of cefpodoxime may lead to overgrowth of non-susceptible organisms. Oral antibiotics may alter the normal microbial flora of the colon, leading to overgrowth of Clostridium and subsequent development of pseudomembranous colitis.

The product should not be administered to infants under 15 days of age, as there are no clinical trial data available in this age group.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this medicinal product. 5 ml of ready-to-use suspension contains 1.8 g of sucrose. This should be taken into account for patients with diabetes mellitus.

The medicinal product contains aspartame (E 951), a source of phenylalanine, and may be harmful to individuals with phenylketonuria.

Use during pregnancy or breastfeeding.

The drug is intended for use in children.

Ability to affect reaction speed when driving or operating machinery.

The drug is intended for use in children.

Dosage and Administration.

Children (from 4 weeks to 12 years of age).

The recommended dose for children is 8 mg/kg/day, administered in two divided doses at 12-hour intervals. A graduated syringe (10 mL) with 0.5 mL graduations is provided with the bottle to ensure accurate dosing.

5 mL of suspension contain the equivalent of 40 mg of cefpodoxime. 1 mL of suspension contains the equivalent of 8 mg of cefpodoxime.

The table below provides administration instructions:

For children with a body weight of at least 25 kg, the dose is 12.5 ml twice daily.

Cefpodoxime should not be used in infants under 15 days of age, as there is no experience with its use in this age group.

Patients with renal impairment.

Dose adjustment of cefpodoxime is not required if creatinine clearance is greater than 40 ml/min/1.73 m2. Pharmacokinetic studies show an increased elimination half-life from plasma when values are below this threshold. Therefore, the dose should be adjusted accordingly as specified in the table below.

Hepatic impairment.

Dose adjustment for patients with hepatic impairment is not required.

Duration

The duration of therapy depends on the patient, the indication, and the causative organism.

Instructions for preparation of the suspension:

The suspension is intended for oral use only. The dose should be taken with food to ensure optimal absorption.

Before preparing the suspension, the silica gel desiccant contained in the capsule inside the cap should be removed and discarded. The suspension is prepared by adding boiled, room-temperature water in two portions (first to 2/3 of the bottle, then to the calibration mark on the bottle), shaking the bottle each time until a thoroughly dispersed suspension is obtained.

For 50 mL of suspension, 20 g of powder and 37 mL of water are required.

For 100 mL of suspension, 40 g of powder and 74 mL of water are required.

SHAKE WELL BEFORE EACH DOSE.

Children.

The drug can be used in children aged from 4 weeks to 12 years. Treatment with the drug is not recommended in infants aged from 4 weeks to 3 months with renal impairment due to lack of experience.

Overdose.

Symptoms: nausea, vomiting, abdominal pain, diarrhea. In patients with renal impairment, overdose may lead to encephalopathy, which is usually reversible after reduction of cefpodoxime plasma levels.

Treatment.

In case of cefpodoxime overdose, supportive and symptomatic therapy should be administered. Hemodialysis, peritoneal dialysis.

Adverse Reactions

The following classification is used to determine the frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000, including isolated cases).

Gastrointestinal disorders:
Common – anorexia, epigastric pressure, gastrointestinal discomfort, nausea, vomiting, abdominal pain, flatulence, diarrhea. Bloody diarrhea may be a symptom of enterocolitis.
Rare – thirst, tenesmus, dyspepsia, dry mouth, decreased appetite, constipation, candidal stomatitis, belching, gastritis, oral ulcers, acute pancreatitis, pseudomembranous colitis.

Metabolism and nutrition disorders:
Common – loss of appetite.
Rare – dehydration, gout, peripheral edema, weight gain.

Immune system disorders:
Uncommon – hypersensitivity.
Rare – anaphylactic reactions, bronchospasm, angioneurotic edema, life-threatening shock.

Hepatobiliary disorders:
Uncommon – cholestatic liver injury.

Laboratory findings:
Uncommon – transient increases in liver transaminase activity (AST, ALT), alkaline phosphatase, and/or bilirubin, urea, and creatinine; pseudopositive Coombs test.
Rare – acute hepatitis.

Blood and lymphatic system disorders:
Rare – hematological disorders such as decreased hemoglobin.
Uncommon – thrombocytosis, thrombocytopenia, leukopenia, eosinophilia, hemolytic anemia, neutropenia, agranulocytosis, lymphocytosis, anemia, leukocytosis.

Respiratory system disorders:
Rare – asthma, cough, epistaxis, rhinitis, wheezing, bronchitis, dyspnea, pleural effusion, pneumonia, sinusitis.

Musculoskeletal system disorders:
Rare – myalgia.

Skin and subcutaneous tissue disorders:
Uncommon – rash, pruritus, urticaria, exanthema, increased sweating, maculopapular rash, fungal dermatitis, desquamation, dry skin, alopecia, vesicular rash, sunburn erythema, purpura, bullous reactions (including Stevens-Johnson syndrome), toxic epidermal necrolysis, exudative multiform erythema, Lyell's syndrome.

Renal and urinary system disorders:
Rare – hematuria, urinary tract infections, metrorrhagia, dysuria, frequent urination, proteinuria, vaginal candidiasis, acute renal failure, slight increases in blood urea and creatinine levels.

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

Cardiovascular system disorders:
Rare – congestive heart failure, migraine, tachycardia, vasodilation, hematoma, arterial hypertension or hypotension.

Nervous system disorders:
Uncommon – headache, paresthesia, dizziness.
Very rare – vertigo, insomnia, somnolence, neurosis, irritability, nervousness, unusual dreams, visual disturbances, confusion, night terrors.

Ear and labyrinth disorders:
Rare – taste disturbances, eye irritation.
Uncommon – tinnitus.

Infections and infestations:
Common – superinfection caused by Candida species resistant to cefpodoxime.
Very rare – antibiotic-associated colitis.

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

Shelf life. 3 years.

Storage conditions.
Store at a temperature not exceeding 25 °C.
The prepared suspension should be stored at 2–8 °C for no more than 14 days.
Keep the container tightly closed.
Keep out of reach of children.

Packaging.
1 bottle of 50 ml or 100 ml with a graduated syringe in a cardboard box.

Prescription category. Prescription only.

Manufacturer.
Sandoz GmbH – Production Division Anti-infectives GLZ and Chemical Operations Kundl (AIHO GLZ Kundl).

Manufacturer's address and site of operations.
Biochemiestrasse 10, 6250 Kundl, Austria.