Iczim

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

Composition:

Active substance: cefixime;

5 ml of suspension contain cefixime trihydrate equivalent to 100 mg of anhydrous cefixime;

Excipients: xanthan gum, sodium benzoate (E 211), flavour (strawberry) 052311 AR0551, colloidal silicon dioxide anhydrous, sucrose.

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties: powder from almost white to light yellow colour, forming a suspension from almost white to yellow colour, with a characteristic fruity odour.

Pharmacotherapeutic group. Antibacterials for systemic use. Beta-lactam antibiotics. Third-generation cephalosporins. ATC code J01D D08.

Pharmacological Properties.

Pharmacodynamics.

Cefixime is a third-generation cephalosporin antibiotic for oral administration. It demonstrates significant bactericidal activity in vitro against a broad spectrum of Gram-positive and Gram-negative microorganisms.

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

Most strains of enterococci (Streptococcus faecalis, Streptococci group D) 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 22–54%. Since food does not significantly affect absorption, cefixime can be administered independently of food intake. Maximum serum concentrations after administration of recommended doses for adults or children range from 1.5 to 3 mcg/mL. With repeated dosing, there is minimal or practically no accumulation of cefixime.

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 on the penetration of cefixime into breast milk.

Clinical characteristics.

Indications.

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

• upper respiratory tract infections (including otitis media) and other upper respiratory tract infections (sinusitis, pharyngitis, tonsillitis of bacterial etiology) in cases of known or suspected resistance of the causative agent to other commonly used antibiotics or in case of risk of ineffective treatment;
• 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, E. coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase-positive and negative), Branhamella catarrhalis (beta-lactamase-positive and negative), and Enterobacter species. Exhibits high stability in the presence of beta-lactamases.

Most strains of enterococci (Streptococcus faecalis, Streptococci group D) 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 types of interactions.

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

Salicylic acid increases the amount 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 its plasma levels is advisable.

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.

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

Antacids containing magnesium or aluminum hydroxide delay drug absorption.

Like other antibiotics, cefixime may reduce the reabsorption of estrogens and decrease the effectiveness of combined oral contraceptives.

With the use of cefixime, as with other cephalosporins, an increased prothrombin time has been observed in some patients; therefore, caution should be exercised if the patient is receiving anticoagulant therapy.

Cefixime should be used with caution in patients receiving anticoagulants of the coumarin type, such as potassium warfarin. Since cefixime may potentiate the effects of anticoagulants, an increase in prothrombin time with or without clinical signs of bleeding is possible.

During treatment with cefixime, a false-positive direct Coombs' test and a false-positive test for glucose in urine using copper sulfate tablets, Benedict's or Fehling's solutions may occur. For determination of glucose in urine, a glucose oxidase test is recommended.

Special precautions.

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

Severe 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.

Hypersensitivity reactions.

Prior to initiating cefixime therapy, 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 administered with caution in patients with any type of allergic condition, particularly drug allergies.

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

Cefixime should be used with caution in patients with significant renal impairment (see "Dosage in renal impairment").

As with other cephalosporins, cefixime may lead to acute renal failure, including tubulointerstitial nephritis as the underlying pathological condition. If acute renal failure develops, cefixime should be discontinued and appropriate therapy and/or interventions initiated.

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

Caution should be exercised when prescribing the drug to patients with a history of bleeding disorders, gastrointestinal diseases, particularly ulcerative colitis, regional enteritis, or antibiotic-associated colitis, as well as in patients with impaired liver function.

The safety of cefixime use in preterm infants or newborns has not been established.

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 resolve after discontinuation, oral vancomycin—considered the drug of choice for pseudomembranous colitis—should be administered.

In cases of moderate to severe colitis, treatment should also include electrolyte and protein solutions. Concomitant use of drugs that reduce intestinal peristalsis should be avoided.

Anemia.

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

Effects on blood system.

Neutropenia and agranulocytosis may occur during treatment with beta-lactam antibiotics, especially with prolonged therapy. Cefixime therapy should be discontinued if neutropenia develops.

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

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.

A positive direct Coombs' test and false-positive urine glucose tests may occur during treatment.

Cephalosporins increase alcohol toxicity; therefore, consumption of alcoholic beverages is not recommended during cefixime therapy.

Important information about certain excipients.

5 mL of reconstituted suspension contains 2.325 g of sucrose. 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.

Izim 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.

Reproduction studies in mice and rats receiving doses nearly 400 times higher than the human dose showed no effects on fertility or fetal abnormalities due to cefixime. In rabbits, at doses up to 4 times the human dose, no evidence of teratogenic effects was observed; however, a high incidence of abortions and maternal mortality occurred, which is an expected consequence of the known sensitivity of rabbits to antibiotic-induced changes in intestinal flora.

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

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

Ability to influence reaction speed when driving or operating machinery.

No effect. However, patients who experience adverse reactions affecting the central nervous system (e.g., dizziness) during Izim use should refrain from driving or operating machinery during treatment.

Dosage and Administration

Food intake does not affect cefixime absorption. The usual duration of treatment is 7 days; if necessary, up to 14 days. For treatment of uncomplicated cystitis, the treatment course is 3 days.

Children aged 6 months to 10 years with body weight below 50 kg: 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 10 years or older (or with body weight above 50 kg): the recommended dose is 400 mg once daily, or 200 mg every 12 hours, depending on the severity of the infection.

Elderly patients: administer the drug at the usual adult dose. Renal function should be monitored and the dose adjusted in cases of severe renal impairment (see "Dosage in Renal Impairment").

Dosage in Renal Impairment: cefixime can be used in patients with impaired renal function. For patients with creatinine clearance of 20 mL/min or higher, administer the standard dose and dosing regimen. For patients with creatinine clearance below 20 mL/min, the daily dose should be reduced by 50%. This also applies to patients undergoing continuous ambulatory peritoneal dialysis or hemodialysis.

Preparation of Suspension.

For oral use only.

Before preparation, invert and shake the bottle to loosen the powder. Add boiled, cooled water up to the mark indicated on the bottle in two portions, shaking the bottle thoroughly each time to form a uniform suspension.

The suspension may be taken no sooner than 5 minutes after preparation.

The prepared suspension must be shaken well before each dose.

Children.

The medicinal product can be used in children aged 6 months and older. 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.

Cases of overdose have not been reported. Adverse reactions observed with cefixime administration at doses up to 2 g in healthy study participants did not differ from those observed 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 contribute only minimally to cefixime elimination from the body.

Adverse Reactions.

Blood and lymphatic system disorders: eosinophilia, hyper-eosinophilia, agranulocytosis, leukopenia, neutropenia, granulocytopenia, hemolytic anemia, thrombocytopenia, thrombocytosis, hypoprothrombinemia, thrombophlebitis, prolonged thrombin and prothrombin time (bleeding and unexplained bruising), purpura.

Gastrointestinal disorders: stomach cramps, abdominal pain, diarrhea*, dyspepsia, nausea, vomiting, flatulence, dysbacteriosis, mucosal candidiasis, stomatitis, glossitis.

Hepatobiliary disorders: jaundice, hepatitis, cholestasis.

Infections and infestations: pseudomembranous colitis.

Laboratory findings: increased aspartate aminotransferase, increased alanine aminotransferase, increased blood bilirubin, increased blood urea, increased serum creatinine.

Metabolism and nutrition disorders: anorexia (loss of appetite).

Nervous system disorders: headache, dizziness, dysphoria; seizures have been reported during treatment with cephalosporins, including cefixime.

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

Ear and labyrinth disorders: hearing loss.

Respiratory, thoracic and mediastinal disorders: dyspnea.

Renal and urinary disorders: acute renal failure, including tubulointerstitial nephritis as the primary pathological condition, hematuria.

Immune system and skin and subcutaneous tissue disorders: anaphylactic reaction; serum sickness-like reactions; drug rash with eosinophilia and systemic symptoms (DRESS); fever; facial swelling, hypersensitivity reactions such as rash, pruritus, drug-induced urticaria, and arthralgia, including rare cases of hives or angioneurotic edema. These reactions usually resolved after discontinuation of therapy; erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

Reproductive system and breast disorders: genital itching, candidal vaginitis.

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

* Diarrhea is usually associated with the use of the drug at the highest doses. Cases of moderate to severe diarrhea have been reported; in such cases, discontinuation of therapy is justified. If severe diarrhea occurs, cefixime should be discontinued.

Shelf life.

2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in a dry, light-protected place.

Keep out of reach of children.

The reconstituted suspension should be stored at a temperature not exceeding 25 °C and used within 14 days.

Packaging.

One 50 ml vial containing powder, together with a measuring cup, in a cardboard package.

Prescription status.

Prescription only.

Manufacturer.

Lupin Limited.

Manufacturer's address and location of operations.

198-202, New Industrial Area No. 2, Mandideep (Unit-1) – 462046, Dist. Raisen, M.P., India.

Marketing Authorization Holder.

Sky Pharma VZ LLC.

Address of the Marketing Authorization Holder.

Unit 708S, 7th Floor, Dubai Science Park (DSP), South Tower, Dubai Science Park, Dubai, United Arab Emirates.