Cefixime deva

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Cefixime Deva (Cefixime Deva)

Composition:

Active substance: cefixime;

One film-coated tablet contains cefixime (as cefixime trihydrate) 400 mg;

Excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose (PH 102), pregelatinized starch, magnesium stearate;

Film coating Opadry White OY-D-7233: hypromellose, titanium dioxide (E 171), talc, propylene glycol/macrogol, sodium lauryl sulfate.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, elongated film-coated tablets with a groove on one side.

Pharmacotherapeutic group.

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

ATC code J01DD08.

Pharmacological properties.

Pharmacodynamics.

Cefixime is an oral third-generation cephalosporin antibiotic. In vitro, it demonstrates potent bactericidal activity against a broad spectrum of gram-positive and gram-negative microorganisms.

It is clinically effective in the treatment of infections caused by the most common pathogenic microorganisms, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase-positive and beta-lactamase-negative strains), Branhamella catarrhalis (beta-lactamase-positive and beta-lactamase-negative strains), and Enterobacter species. It exhibits a high degree of stability in the presence of beta-lactamases.

Most strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase-positive, coagulase-negative, and methicillin-resistant strains) are resistant to cefixime. In addition, most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes, and Clostridia are resistant to cefixime.

Pharmacokinetics.

Absorption. Absolute bioavailability following oral administration of cefixime ranges from 22% to 54%. Since food does not significantly affect absorption, cefixime can be administered regardless of food intake.

The peak serum concentration after administration of recommended doses in adults or children ranges from 1.5 to 3 mcg/mL. With repeated dosing, accumulation of cefixime is minimal or absent. Pharmacokinetics of cefixime were compared in healthy elderly patients (aged >64 years) and young volunteers (aged 11–35 years) after administration of 400 mg cefixime once daily for 5 days. Mean Cmax and AUC values were slightly higher in elderly patients. However, dosage adjustment is not required in elderly patients, and the same dosage regimens as for adults are recommended.

Distribution. Cefixime is almost entirely bound to the albumin fraction, with the mean free fraction being approximately 30%.

Metabolism. Metabolites of cefixime have not been identified in human serum or urine.

Elimination. Cefixime is excreted predominantly unchanged in the urine. The primary mechanism is glomerular filtration.

There are no data available regarding the penetration of cefixime into breast milk.

Clinical characteristics.

Indications.

Infectious-inflammatory diseases caused by microorganisms sensitive to the drug:

• infections of the upper respiratory tract (including otitis media) and other upper respiratory tract infections (sinusitis, pharyngitis, tonsillitis of bacterial etiology) in cases of known or suspected resistance of the pathogen to other commonly used antibiotics, or in case of risk of treatment inefficacy;
• lower respiratory tract infections (including acute bronchitis and exacerbations of chronic bronchitis);
• urinary tract infections (including cystitis, cystourethritis, uncomplicated pyelonephritis).

Clinically effective in the treatment of infections caused by the most common pathogenic microorganisms, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase-positive and beta-lactamase-negative), Branhamella catarrhalis (beta-lactamase-positive and beta-lactamase-negative), and Enterobacter species. Exhibits high stability in the presence of beta-lactamases.

Most strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase-positive, coagulase-negative, and methicillin-resistant strains) are resistant to cefixime. In addition, most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes, and Clostridia are resistant to cefixime.

Contraindications.

• Confirmed hypersensitivity to cephalosporin antibiotics or to any other components of the medicinal product.
• Hypersensitivity to penicillins; porphyria.

Interaction with other medicinal products and other types of interactions.

As with other cephalosporins, increased prothrombin time has been observed in some patients; therefore, caution should be exercised in patients receiving anticoagulant therapy.

Cefixime should be used with caution in patients receiving anticoagulants such as coumarins, for example, potassium warfarin. Since cefixime may potentiate the effect of anticoagulants, an increase in prothrombin time, with or without clinical signs of bleeding, may occur.

Tubular secretion blockers (allopurinol, probenecid, diuretics) increase the maximum serum concentration of cefixime by slowing its renal excretion, which may lead to symptoms of overdose.

When cefixime is used concomitantly with potentially nephrotoxic substances (aminoglycosides, colistin, polymyxin, viomycin) or potent diuretics (ethacrynic acid, furosemide), there is an increased risk of developing renal failure.

Salicylic acid increases the level of free cefixime by 50% due to displacement of cefixime from protein-binding sites. This effect is concentration-dependent.

Concomitant use with carbamazepine may increase its plasma concentration; therefore, monitoring of plasma carbamazepine levels is advisable.

Nifedipine increases the bioavailability of cefixime, but clinical interaction has not been established.

Use of the medicinal product may reduce reabsorption of estrogens and decrease the effectiveness of combined oral contraceptives.

During treatment with cefixime, false-positive glucose in urine tests may occur when using copper sulfate tablets, Benedict's or Fehling's solutions. Glucose oxidase tests are recommended for determining glucose in urine.

Cephalosporin antibiotics may cause false-positive results in the direct Coombs test. Therefore, it should be noted that a positive Coombs test result may be due to the use of this medicinal product.

Special precautions for use.

Encephalopathy.

Beta-lactams, including cefixime, may increase the risk of encephalopathy (which may include seizures, confusion, impaired consciousness, movement disorders) in patients, particularly in cases of overdose and renal impairment.

Severe skin reactions.

Serious skin adverse reactions, such as toxic epidermal necrolysis, Stevens–Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported in some patients receiving cefixime. If severe skin adverse reactions occur, cefixime should be discontinued and appropriate treatment initiated and/or necessary preventive measures taken.

Anemia.

Cases of drug-induced hemolytic anemia, including severe cases with fatal outcomes, have been reported during treatment with cephalosporins. Hemolytic anemia has also been reported following re-administration of cephalosporins (including cefixime).

Effect on kidney function.

Cefixime should be administered with caution to patients with significant renal impairment (see "Dosage and administration. Renal failure").

As with other cephalosporins, cefixime may lead to acute kidney injury, including tubulointerstitial nephritis as the primary pathological condition. If acute kidney injury occurs, cefixime should be discontinued and appropriate therapy initiated and/or appropriate measures taken.

When cefixime is used in high doses concomitantly with aminoglycosides, polymyxin B, colistin, or loop diuretics (furosemide, ethacrynic acid), renal function should be closely monitored. After prolonged use of cefixime, hematopoietic function should be evaluated.

Hypersensitivity reactions.

Prior to initiating treatment with cefixime, it is essential to determine whether the patient has a history of hypersensitivity reactions to cephalosporins, penicillins, or other medicinal products.

Antibiotics, including cefixime, should be used with caution in patients with any type of allergic reaction, particularly to medicinal products.

If an allergic reaction occurs, the drug should be discontinued and appropriate treatment initiated. Allergic reactions (particularly anaphylaxis) associated with beta-lactam antibiotics may be severe and, in rare cases, fatal (see "Adverse reactions").

Colitis/overgrowth of non-susceptible microorganisms.

Adverse reactions affecting the gastrointestinal tract may occur during treatment; therefore, cefixime should be administered with caution in patients with a history of gastrointestinal bleeding, gastrointestinal disorders (particularly ulcerative colitis, regional colitis, or enteritis), or hepatic dysfunction.

Prolonged use of cefixime may lead to overgrowth of non-susceptible microorganisms, including disruption of normal intestinal flora, which may result in overgrowth of Candida albicans and development of oral mucosal candidiasis (see "Adverse reactions").

Pseudomembranous colitis.

Broad-spectrum antibiotics, particularly when used long-term, may lead to the development of pseudomembranous colitis. Symptoms of pseudomembranous colitis may develop during or after completion of antibiotic therapy.

The onset of severe diarrhea during treatment may indicate pseudomembranous colitis. In such cases, cefixime should be discontinued and appropriate diagnostic evaluation performed.

Effect on blood system.

Neutropenia and agranulocytosis may occur during treatment with beta-lactam antibiotics, particularly with prolonged therapy. If neutropenia develops, treatment with cefixime should be discontinued.

Blood counts should be monitored during prolonged treatment (more than 10 days).

Effect on serological test results.

Cefixime may cause false-positive results in the Coombs test. Cefixime may also lead to false-positive urine glucose tests (see "Adverse reactions").

Antibacterial spectrum.

For infections caused by group A beta-hemolytic streptococci, the treatment course should last at least 10 days to prevent acute rheumatic fever.

Interaction with alcohol.

Cephalosporins enhance the toxicity of alcohol; therefore, consumption of alcoholic beverages is not recommended during treatment with cefixime.

Use during pregnancy or breastfeeding.

There are no data on the use of cefixime during pregnancy. Cefixime crosses the placental barrier.

Breastfeeding should be discontinued during treatment with this drug.

The medicinal product should not be used during pregnancy or breastfeeding except in cases of extreme necessity and under medical supervision.

Ability to affect reaction speed when driving or operating machinery.

The possibility of central nervous system adverse reactions (e.g., dizziness) should be considered, as they may impair psychomotor performance. In such cases, patients should refrain from driving or operating machinery.

Dosage and Administration

The medicinal product can be taken independently of food intake.

The duration of treatment depends on the severity of the disease and is determined individually. Usually, the treatment course lasts 7 days, or 14 days if necessary. In infections caused by Streptococcus pyogenes, the treatment course should be at least 10 days. For treatment of uncomplicated cystitis, the treatment course is 3 days.

Adults and children aged 12 years and older: the recommended dose is 400 mg (1 tablet) once or twice daily.

For treatment of uncomplicated urethral or cervical gonococcal infections, a single dose of 400 mg is recommended.

Elderly patients: administer the drug at the recommended adult dose.

Renal impairment: cefixime can be used in patients with impaired renal function. For patients with a creatinine clearance of 20 mL/min or higher, the usual dose and dosing regimen should be used. For patients with creatinine clearance below 20 mL/min, the dose should not exceed 200 mg (half a tablet) once daily. This also applies to patients undergoing continuous ambulatory peritoneal dialysis or hemodialysis.

Children.

The drug is not recommended for children under 12 years of age; an alternative pharmaceutical form is recommended for this age group.

Overdose.

There is a risk of encephalopathy when administering beta-lactam antibiotics, including cefixime, especially in cases of overdose and renal impairment.

Adverse reactions observed with doses up to 2 g in healthy volunteers did not differ from those seen in patients receiving the drug at recommended doses.

Symptoms: intensification of adverse reactions.

Treatment: gastric lavage, symptomatic and supportive therapy. There is no specific antidote. Hemodialysis or peritoneal dialysis contributes only minimally to the elimination of cefixime from the body.

Adverse Reactions

Adverse reactions caused by cefixime are generally mild and occur infrequently. Possible disorders include:

Nervous system disorders: headache, dizziness, dysphoria; convulsions have been reported during treatment with cephalosporins, including cefixime (frequency unknown).

Beta-lactams, including cefixime, may increase the risk of encephalopathy (which may include convulsions, confusion, altered consciousness, and movement disorders) in patients, particularly in cases of overdose and renal impairment (frequency unknown).

Auditory and vestibular system disorders: hearing loss.

Respiratory system disorders: dyspnea.

Blood and lymphatic system disorders: eosinophilia, granulocytopenia, leukopenia, thrombocytopenia, thrombocytosis, neutropenia, hemolytic anemia, hypoprothrombinemia (bleeding and bruising without apparent cause), thrombophlebitis, prolonged thrombin and prothrombin time, agranulocytosis.

Gastrointestinal disorders: abdominal cramps, abdominal pain, diarrhea*, nausea, vomiting, oral candidiasis, pseudomembranous colitis, dry mouth, dyspepsia, flatulence, dysbacteriosis, stomatitis, glossitis (rare cases).

Metabolism and nutrition disorders: anorexia.

Hepatobiliary system disorders: hepatitis, cholestasis, transient increases in liver transaminase and alkaline phosphatase activity, hyperbilirubinemia, cholestatic jaundice, scleral icterus, skin icterus.

Renal and urinary system disorders: acute renal failure, including interstitial nephritis as the main pathological condition, hematuria.

Immune system, skin and subcutaneous tissue disorders: hypersensitivity reactions, including: rash, pruritus, angioneurotic edema, anaphylactic shock, anaphylactic reactions; serum sickness-like reactions; drug reaction with eosinophilia and systemic symptoms (DRESS); facial swelling, skin hyperemia, urticaria, erythema multiforme or Stevens–Johnson syndrome, serum sickness, purpura, arthralgia, fever, maculopapular and vesiculobullous rashes, fungal dermatitis, epithelial desquamation, dry skin, hair loss, sunburn, toxic epidermal necrolysis.

Reproductive system and breast disorders: genital pruritus, Candida-induced vaginitis.

Infections and infestations: vaginal candidiasis (vaginal itching or discharge).

Cases of diarrhea following cefixime administration may be associated with Clostridium difficile.

Laboratory findings: most laboratory changes are transient and not clinically significant. Possible increases in blood urea nitrogen and serum creatinine levels, false-positive Coombs test results. A positive ketone reaction in urine may occur with nitroprusside-based tests, but not with nitroferrocyanide. Cefixime may cause false-positive glucose in urine tests (therefore, enzymatic tests should be used). Changes in liver and kidney function test parameters may also occur.

General disorders: increased sweating, fatigue, weakness, mucosal inflammation.

* Diarrhea is usually associated with higher doses of the drug. Cases of diarrhea (from moderate to severe) have been reported; in such cases, discontinuation of therapy is warranted. If severe diarrhea occurs, cefixime should be discontinued.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after drug authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

5 film-coated tablets in a blister; 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Deva Holding A.Ş.

Manufacturer's address and location of operations.

Çerkezköy Organize Sanayi Bölgesi Karaağaç Mah. Atatürk Cad. No: 32 Kapaklı / Tekirdağ / Turkey.