Cefma

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

Composition:

Active substance: cefpodoxime;

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

Excipients: sodium lauryl sulfate, magnesium stearate, hydroxypropylcellulose, crospovidone, lactose monohydrate, calcium carboxymethylcellulose, titanium dioxide (E 171), talc, hypromellose.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, film-coated tablets with a score line on both sides, white to yellowish in color.

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

Pharmacological properties.

Pharmacodynamics.

The mechanism of antibacterial action of cefpodoxime is based on inhibition of bacterial cell wall synthesis (during the growth phase) by inhibiting penicillin-binding proteins (PBPs), such as transpeptidases. This leads to disruption of cell wall biosynthesis (peptidoglycan), resulting in lysis and death of bacterial cells.

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; Streptococci group A (S. pyogenes), B (S. agalactiae), 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 (strains producing and not producing β-lactamase); Haemophilus parainfluenzae (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 sensitivity against: methicillin-sensitive staphylococci, strains producing and not producing penicillinase (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.

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

Pharmacokinetics.

Cefpodoxime proxetil is absorbed in the intestine and hydrolyzed to its active metabolite, cefpodoxime. After oral administration of cefpodoxime proxetil on an empty stomach in tablet form equivalent to 100 mg of cefpodoxime, 51.1% is absorbed, and absorption increases when taken with food. The volume of distribution is 32.3 L, and peak levels of cefpodoxime are observed 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. Following administration of 100 mg and 200 mg doses twice daily for 14.5 days, the pharmacokinetic parameters of cefpodoxime in plasma remain unchanged. Protein binding of cefpodoxime to serum proteins, primarily albumin, is 40%. 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 prostate tissue. Studies in healthy volunteers show that mean 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, high concentrations are achieved (concentrations in urine fractions collected 0–4, 4–8, and 8–12 hours after a single dose exceed the MIC₉₀ for common urinary pathogens). Good diffusion of cefpodoxime is also observed in renal tissue, 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; approximately 80% of the dose is excreted unchanged in urine with a half-life of approximately 2.4 hours.

Clinical characteristics.

Indications.

Treatment of infections caused by pathogens sensitive to the drug:

• Infections of the ear, nose, and throat (including sinusitis, tonsillitis, pharyngitis); for the treatment of tonsillitis and pharyngitis, cefpodoxime should be prescribed in cases of chronic or recurrent infection, as well as in cases of known or suspected resistance of the pathogen to commonly used antibiotics;
• 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 cefpodoxime, cephalosporin-class drugs, or to any component of the medicinal product.

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

Rare hereditary conditions: 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 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 concomitantly with agents that neutralize gastric pH or inhibit acid secretion. Therefore, such agents as antacids and H₂-blockers, which may lead to increased gastric pH, should be taken 2–3 hours after administration of cefpodoxime.

The bioavailability of the drug increases when taken with food.

Cefpodoxime should not be used concomitantly with bacteriostatic antibiotics (e.g., chloramphenicol, erythromycin, sulfonamides, or tetracyclines), as the therapeutic 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, but such a reaction has not been observed with tests based on enzymatic glucose oxidase reactions.

Special precautions for use.

Before initiating therapy, it is necessary to determine whether the patient has had any history of hypersensitivity reactions to cefpodoxime, cephalosporins, penicillins, or other beta-lactam antibiotics.

This medicinal product is contraindicated in patients who have had 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 particular caution, as the risk of serious hypersensitivity reactions is increased in such cases.

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

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

Cefpodoxime is not the antibiotic of first 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.

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).

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

Testing for the presence of C. difficile should be performed. In case of suspected colitis, treatment should be stopped immediately. Diagnosis should be confirmed by sigmoidoscopy and/or rectoscopy, and if clinically indicated, an alternative antibiotic (e.g., vancomycin) should be prescribed. Medications that cause fecal retention should be avoided. When using broad-spectrum agents such as cephalosporins, the risk of developing pseudomembranous colitis is increased.

As with all beta-lactam antibiotics, neutropenia and, more rarely, agranulocytosis may develop, especially during prolonged treatment. If the treatment course lasts longer than 10 days, blood counts should be monitored, 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. This may lead to a positive Coombs test and, very rarely, to hemolytic anemia. Cross-reactivity with penicillin may occur in this reaction.

The Coombs test and non-enzymatic methods for measuring urinary glucose may yield false-positive results during cephalosporin therapy.

Changes in renal function have been observed during treatment with cephalosporin antibiotics, particularly when administered concomitantly with potentially nephrotoxic agents such as aminoglycosides and/or diuretics (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 below 40 mL/min and for patients undergoing hemodialysis, the dosing interval should be extended.

If exudative multiform erythema, Stevens-Johnson syndrome, or Lyell’s syndrome occur, 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 large intestine, leading to overgrowth of Clostridium species and subsequent development of pseudomembranous colitis.

This medicinal product contains lactose. If the patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding.

Clinical data on the effects of cefpodoxime during pregnancy are lacking. In animal studies, no teratogenic or fetotoxic effects of cefpodoxime have been observed. However, the safety of cefpodoxime during pregnancy has not been established; therefore, the drug should be used with caution only after careful assessment of the benefit-risk ratio, particularly during the first trimester of pregnancy.

Cefpodoxime passes into breast milk in very small amounts. Therefore, changes in intestinal flora, including diarrhea and colonization with yeast-like fungi, may occur in breastfed infants, which may necessitate discontinuation of breastfeeding. The possibility of sensitization should also be considered. Therefore, cefpodoxime should be used during breastfeeding only after careful assessment of the benefit-risk ratio.

Ability to affect reaction speed when driving or operating machinery.

Cefpodoxime has a weak or moderate effect on reaction speed when driving or operating machinery.

Dizziness or hypotension have been reported during cefpodoxime therapy, which may affect patients' reaction speed when driving or operating machinery.

Method of administration and dosage.

The drug should be administered orally. For optimal absorption, the tablet should be taken with food. The 200 mg tablet may be divided into two parts.

Adults and adolescents with normal renal function.

Sinusitis: 200 mg twice daily.

Tonsillitis and pharyngitis: 100 mg (½ tablet) twice daily.

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

Uncomplicated lower urinary tract infections: 100 mg (½ tablet) 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 is not required for elderly patients with normal renal function.

Hepatic impairment. Dose adjustment is not required for patients with hepatic impairment.

Renal impairment. Appropriate dose adjustment is required for patients with impaired renal function (creatinine clearance < 40 mL/min).

1. Single dose – 100 mg or 200 mg depending on the type of infection, as indicated above.

The duration of therapy depends on the patient, the indication, and the causative agent. Usually, the treatment duration is 5–10 days. When treating infections caused by Streptococcus pyogenes, therapy should last for 10 days.

Children.

Tablets are indicated for children aged 12 years and older at a dose of 100 mg (½ tablet) twice daily.

Overdose.

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

Treatment: in case of overdose, provide supportive and symptomatic therapy. Hemodialysis, peritoneal dialysis.

Adverse Reactions.

The following frequency classification was used to determine the incidence of adverse reactions: 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, 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 and angioedema; life-threatening shock.

Hepatobiliary disorders: uncommon – cholestatic liver injury; rare – acute hepatitis.

Laboratory findings: uncommon – transient increases in liver enzyme activity (alanine and aspartate aminotransferases), alkaline phosphatase, and/or bilirubin, urea, and creatinine; Coombs test pseudopositive reaction.

Blood and lymphatic system disorders: rare – hematological disorders such as agranulocytosis, hemolytic anemia, eosinophilia, lymphocytosis, anemia, leukopenia, neutropenia, leukocytosis, thrombocytopenia; uncommon – reversible thrombocytosis.

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

Musculoskeletal and connective tissue 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 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 the use of 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.

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

Eye and ear disorders: rare – taste disturbances, eye irritation; uncommon – tinnitus.

Infections and infestations: common – superinfection caused by some Candida species not sensitive 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.

If adverse effects or unwanted reactions occur, a physician must be informed immediately.

Shelf life. 3 years.

Storage conditions.

No special storage conditions required.

Store in the original packaging. Keep out of reach of children.

Incompatibility.

No data available.

Packaging.

10 tablets in a blister pack. 1 (10×1) or 2 (10×2) blister packs in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Sandoz GmbH – Production Division Anti-Infectives GLZ and Chemical Operations Kundl (AIC GLZ Kundl).

Manufacturer's address and location of business operations.

Biochemiestrasse 10, 6250 Kundl, Austria