CEFIXIME DEVA

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

Composition:

Active substance: cefixime;

100 mg of cefixime (as cefixime trihydrate) in 5 ml of suspension;

Excipients: sucrose, xanthan gum, sodium benzoate (E 211), raspberry flavor, colloidal silicon dioxide.

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties: white or almost white powder which forms a white to almost white suspension with a characteristic raspberry odor.

Pharmacotherapeutic group.

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

ATC J01D D08.

Pharmacological properties.

Pharmacodynamics.

Cefixime is an oral third-generation cephalosporin antibiotic. In vitro, it demonstrates significant 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 has 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 after oral administration of cefixime ranges from 22% to 54%. Since the presence of food does not significantly affect absorption, cefixime can be administered regardless of food intake.

The maximum 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 elderly patients (aged >64 years) and young volunteers (aged 11–35 years) after administration of 400 mg of cefixime once daily for 5 days. Mean Cmax and AUC values were slightly higher in elderly patients. However, elderly patients can be given the same dosage as adults.

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

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

Excretion. Cefixime is excreted primarily unchanged in the urine. The predominant 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, bacterial tonsillitis) in cases of known or suspected resistance of the causative agent 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. Highly stable 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 other components of the medicinal product.
• Hypersensitivity to penicillins; porphyria.

Interaction with other medicinal products and other forms of interaction.

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, e.g., potassium warfarin. Since cefixime may potentiate the effect of anticoagulants, an increase in prothrombin time may occur, with or without clinical signs of bleeding.

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

When cefixime is used concomitantly with potentially nephrotoxic agents (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 lead to increased plasma concentration of carbamazepine; therefore, monitoring of carbamazepine plasma 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 test is recommended for determination of 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.

Encephalopathy.

Beta-lactams, including cefixime, may increase the risk of encephalopathy (which may include seizures, confusion, impaired consciousness, movement disorders) in patients, especially 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 repeated administration of cephalosporins, including cefixime.

Effect on kidney function.

Cefixime should be administered with caution in patients with significant renal impairment (see "Dosage and administration. Dosing in renal impairment").

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 treatment initiated and/or necessary preventive 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. Hematopoietic function should be checked after prolonged use of cefixime.

Hypersensitivity reactions.

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

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

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

Colitis/overgrowth of resistant microorganisms.

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

Prolonged use of cefixime may lead to overgrowth of resistant 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, especially 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 the 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").

Spectrum of antibacterial activity.

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

Important information about certain excipients.

Cefixime Deva, powder for oral suspension, contains sucrose as an excipient. This should be taken into account in patients with diabetes mellitus.

The medicinal product should not be administered to patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency.

Cefixime Deva may be harmful to teeth. It is recommended to rinse the mouth with water after administration; children should drink sufficient water after taking the medication.

Use during pregnancy or breastfeeding.

There is no data available on the use of the drug during pregnancy. Cefixime crosses the placenta.

Breastfeeding should be discontinued during treatment with the drug.

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

Ability to affect reaction speed when driving or operating machinery.

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

Method of Administration and Dosage.

Food intake does not affect cefixime absorption. The duration of treatment depends on the severity of the disease and is determined individually. Usually, the treatment course lasts 7 days; if necessary, 14 days. In the treatment of uncomplicated cystitis, the treatment course is 3 days.

Children aged 6 months to 12 years: The recommended dose is 8 mg/kg once daily or 4 mg/kg every 12 hours, depending on the severity of the infection.

Adults and children aged 12 years and older: The recommended dose is 400 mg once daily or 200 mg every 12 hours, depending on the severity of the infection.

Elderly patients: No special precautions are required. Elderly patients may be given the same dose as adults, divided into two doses of 4 mg/kg every 12 hours.

Dosing in 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 administered. For patients with a creatinine clearance below 20 mL/min, the daily dose should be reduced by 50% (i.e., 200 mg once daily). This also applies to patients undergoing chronic ambulatory peritoneal dialysis or hemodialysis.

Dosing in hepatic impairment: Dose adjustment is not required.

Method of Suspension Preparation.

Before preparation, shake the bottle to loosen the powder.

Gradually add boiled, cooled water up to the 2/3 mark (line) on the bottle and shake thoroughly.

Allow to stand for 5 minutes to ensure complete dissolution.

Add boiled, cooled water up to the full mark (line) on the bottle (the remaining 1/3) and shake thoroughly again.

The recommended dose should be administered using the measuring spoon provided in the package.

Each 5 mL of prepared suspension (1 measuring spoon) contains 100 mg of cefixime.

The prepared suspension must be shaken well before each use.

Children.

The drug is indicated for children aged 6 months and older. The safety and efficacy of cefixime in children under 6 months of age have not been established; therefore, cefixime is not recommended for use in this patient group.

Overdose.

There is a risk of encephalopathy when using 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 were not different from those seen in patients receiving the drug at recommended doses.

Symptoms: Exaggeration of adverse reactions.

Treatment: Gastric lavage, symptomatic and supportive therapy. There is no specific antidote. Hemodialysis or peritoneal dialysis only slightly enhances cefixime elimination from the body.

Adverse Reactions

Adverse reactions caused by cefixime are generally mild and occur infrequently.

The following adverse events may occur:

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

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

Ear and labyrinth 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 prothrombin and thrombin time, agranulocytosis.

Gastrointestinal disorders: Spasms in the stomach and intestines, abdominal pain, diarrhea*, nausea, vomiting, oral candidiasis, pseudomembranous colitis, dry mouth, dyspepsia, flatulence, dysbacteriosis, and in isolated cases – stomatitis, glossitis.

Metabolism and nutrition disorders: Anorexia.

Hepatobiliary disorders: Hepatitis, cholestasis, transient increases in liver transaminase and alkaline phosphatase activity, hyperbilirubinemia, jaundice of the sclera, jaundice of the skin.

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 abnormalities are transient and clinically insignificant. Possible increases in blood urea nitrogen and serum creatinine levels, false-positive results in the Coombs test. A positive reaction for ketones in urine may also occur in tests using nitroprusside, but not nitroferricyanide. Cefixime intake may cause false-positive results in urine glucose 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 may be warranted.

Cefixime should be discontinued if severe diarrhea occurs.

Reporting of adverse reactions following marketing authorization of the medicinal product is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to 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 powder at a temperature not exceeding 25 °C.

Store the prepared suspension at a temperature not exceeding 25 °C and use within 14 days.

Keep out of the reach of children.

Packaging.

1 vial of powder (for 100 mL of suspension) with a plastic dosing spoon, in a 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