Iczim

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IKZYM (IXIME)

Composition:

Active substance: cefixime;

One tablet contains cefixime trihydrate equivalent to cefixime 400 mg;

Excipients: microcrystalline cellulose, pregelatinized starch, low-substituted hydroxypropyl cellulose, sodium croscarmellose, colloidal silicon dioxide, magnesium stearate; coating: Instacoat Universal- IC-U-1308.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets, white to almost white, oval-shaped, with a biconvex surface.

Pharmacotherapeutic group. Antibiotic of the third-generation cephalosporin group.

ATC code J01D D08.

Pharmacological Properties.

Pharmacodynamics.

Mechanism of action. Cefixime is a semi-synthetic antibiotic of the third-generation cephalosporin class for oral administration. It has bactericidal activity. Its mechanism of action is related to the inhibition of bacterial cell wall synthesis. Cefixime is stable against the action of beta-lactamases produced by many Gram-positive and Gram-negative bacteria.

Spectrum of activity.
Gram-positive bacteria: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae.
Gram-negative bacteria: Neisseria gonorrhoeae, Moraxella catarrhalis, Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella pneumoniae, Klebsiella oxytoca, Pasteurella multocida, Providencia spp., Salmonella spp., Shigella spp., Citrobacter amalonaticus, Citrobacter diversus.

Resistant to cefixime are Pseudomonas spp., Enterococcus spp., Listeria monocytogenes, most staphylococci (including methicillin-resistant strains), Bacteroides fragilis, and Clostridium spp. Activity against Enterobacter spp. and Serratia marcescens is variable.

In clinical practice, cefixime is active against the following Gram-positive bacteria: Streptococcus pneumoniae, Streptococcus pyogenes; and Gram-negative bacteria: Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, Escherichia coli, Proteus mirabilis, Neisseria gonorrhoeae.

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 μg/mL. With repeated administration, slight accumulation of cefixime may occur.

Distribution. Cefixime is almost completely 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 on the penetration of cefixime into breast milk.

Clinical characteristics.

Indications.

Infectious and inflammatory diseases caused by microorganisms sensitive to cefixime:

• respiratory tract infections;
• infections of the ear, nose, and throat (ENT);
• acute and chronic urinary tract infections.

Contraindications.

Hypersensitivity to cefixime or any other component of the medicinal product, as well as to other cephalosporins or penicillins (see section "Special precautions for use"). Porphyria.

Interaction with other medicinal products and other forms of interaction.

Probenecid (and other tubular secretion blockers) increases the maximum blood concentration of cefixime by slowing its renal excretion, which may lead to overdose.

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

Carbamazepine may cause an increase in cefixime plasma concentration; therefore, monitoring of plasma levels is advisable.

Nifedipine increases the bioavailability of cefixime.

Furosemide and aminoglycosides enhance the nephrotoxicity of the drug.

During the use of antibiotics, including cefixime, reduced reabsorption of estrogens and decreased efficacy of combined oral contraceptives may occur.

Coumarin-type anticoagulants.

Cefixime should be used with caution in patients receiving anticoagulant therapy, such as warfarin. Since cefixime can potentiate the effect of anticoagulants, prolongation of prothrombin time may occur, with or without clinical signs of bleeding.

Other forms of interactions: the use of cephalosporins may cause false-positive reactions when testing for glucose in urine using Benedict's or Fehling's solutions or Clinistix tablets. During cefixime administration, a false-positive result in the direct Coombs test is possible.

Special precautions.

Serious skin reactions

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

Hypersensitivity reactions

Prior to administration of cefixime, a careful evaluation of the patient's history regarding hypersensitivity reactions to penicillins, cephalosporins, or other drugs should be performed.

IKZIM should be administered with caution to patients with allergic reactions to penicillins. Evidence from both in vivo (in the human body) and in vitro studies has demonstrated cross-allergic reactions between penicillins and cephalosporins. Such cases are rare but may occur in an anaphylactic manner, particularly after parenteral administration.

Antibiotics should be used with caution in patients with a history of any type of hypersensitivity reactions, especially following administration of medicinal products. If an allergic reaction occurs, the drug should be discontinued immediately.

Alterations in intestinal flora

Prolonged use of antibacterial agents may lead to overgrowth of resistant microorganisms and disruption of normal intestinal flora, potentially resulting in overgrowth of Clostridium difficile and development of pseudomembranous colitis. In mild cases of antibiotic-associated pseudomembranous colitis, discontinuation of the drug may be sufficient. If colitis symptoms do not improve after discontinuation, oral vancomycin — the antibiotic of choice for pseudomembranous colitis — should be prescribed.

In cases of moderate to severe colitis requiring treatment, electrolyte and protein solutions should be added. Concomitant use of medicinal products that reduce intestinal peristalsis should be avoided. Broad-spectrum antibiotics should be prescribed with caution to patients with a history of gastrointestinal disorders, particularly colitis.

Laboratory test data

During treatment with the medicinal product IKZIM, reversible changes in liver and kidney function tests, as well as in blood parameters (thrombocytopenia, leukopenia, and eosinophilia), may occur.

Renal impairment

For patients with severe renal impairment and for patients undergoing hemodialysis or peritoneal dialysis, the dose of IKZIM should be appropriately reduced (see section "Dosage and administration").

Anemia

Cases of hemolytic anemia, including severe cases with fatal outcomes, have been reported following administration of cephalosporins, including cefixime. Recurrent episodes of hemolytic anemia have also been reported in patients who previously developed hemolytic anemia after initial exposure to cephalosporins, including cefixime.

Use during pregnancy or breastfeeding

The medicinal product should be used during pregnancy or breastfeeding only if clearly needed and under physician supervision. Data on embryotoxicity are lacking; however, use of the medicinal product during the first trimester of pregnancy should be avoided. It is unknown whether cefixime is excreted in human breast milk.

Ability to influence reaction rate while driving or operating machinery

Administration of the medicinal product IKZIM does not affect reaction speed while driving or operating machinery. However, if dizziness occurs, patients should avoid driving or operating machinery.

Dosage and Administration.

For adults and children aged 12 years and older, the daily dose is 400 mg given in 1 or 2 doses.

The medicinal product can be taken independently of food intake.

The duration of treatment depends on the nature of the disease course and the type of infection. After the disappearance of infection symptoms and/or fever, it is advisable to continue taking the drug for at least 48–72 hours.

To prevent complications, treatment with cefixime for upper respiratory tract or urinary tract infections should usually last 5–10 days, and for lower respiratory tract infections — 10–14 days.

Treatment of otitis media usually lasts 10–14 days.

For infections caused by group A beta-hemolytic streptococci, to prevent the development of late complications (acute rheumatic fever, glomerulonephritis), treatment should last at least 10 days.

For uncomplicated lower urinary tract infections in women, the drug may be administered for 1–3 days.

The medicinal product should be administered with caution in patients with renal impairment; when creatinine clearance is ≤ 20 mL/min, the daily dose should be reduced to 200 mg.

For elderly patients, there are no dosage precautions related to age.

Children.

IKZIM in film-coated tablets should be administered to children aged 12 years and older (for younger children, a suspension is recommended — for accurate dosing).

Overdose.

It has been shown that in healthy volunteers, administration of doses up to 2 g per day has the same safety profile as recommended therapeutic doses.

Symptoms: intensification of adverse reactions.

Treatment: gastric lavage; symptomatic and supportive therapy.

Hemodialysis and peritoneal dialysis are ineffective. There is no specific antidote.

Adverse reactions

Gastrointestinal disturbances are the most commonly observed adverse effects during the use of cephalosporins.

Hypersensitivity reactions occur rarely, mostly in patients who have previously experienced hypersensitivity reactions, as well as in patients with a history of allergies, hay fever, urticaria, or bronchial asthma with an allergic component.

Rare adverse reactions reported with cefixime use include:

Gastrointestinal system: glossitis, nausea, vomiting, heartburn, abdominal pain, diarrhea, dyspepsia, oral candidiasis, stomatitis, flatulence. Switching to 200 mg twice daily may alleviate diarrhea. Severe, prolonged diarrhea may be associated with the use of certain classes of antibiotics. In such cases, pseudomembranous colitis should be considered in the differential diagnosis. If the diagnosis is confirmed by colonoscopy, all antibiotic therapy must be discontinued immediately and oral vancomycin should be initiated. Medicinal products that reduce intestinal peristalsis are contraindicated.

Immune system: serum sickness-like reactions, anaphylaxis, arthralgia, drug fever, interstitial nephritis.

Blood system: transient leukopenia, agranulocytosis, pancytopenia, transient neutropenia, granulocytopenia, thrombocytopenia, eosinophilia. Hemolytic anemia has been observed in patients receiving cephalosporins. Isolated cases of impaired blood coagulation have also been reported.

Liver: jaundice, transient elevations in transaminase levels (aspartate aminotransferase, alanine aminotransferase), alkaline phosphatase, and total bilirubin; isolated cases of hepatitis.

Urinary system: transient increases in blood urea and serum creatinine levels; acute renal failure, including tubulointerstitial nephritis.

Respiratory system: dyspnea.

Skin: urticaria, skin rashes, pruritus, erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS).

Nervous system: headache, dizziness, dysphoria.

Ear and vestibular system: hearing loss.

General disorders: fever, facial swelling.

Other: anorexia, Candida-induced vaginitis, genital pruritus.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 30 °C.

Packaging. 10 tablets in a blister pack, 1 blister pack in a cardboard box.

Prescription status. Prescription only.

Manufacturer:

Sens Laboratory Pvt. Ltd.

Manufacturer's address and location of operations:

VI/51B, Postcode No. 2, Kozhuvanal, Pala, Kottayam – 686 573, Kerala, India.