Insym - 100

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IНСІМ - 100 (INCIM - 100)

Composition:

Active ingredient: cefixime;

5 ml of oral suspension contain cefixime trihydrate equivalent to 100 mg of cefixime;
Excipients: sucrose, xanthan gum, colloidal anhydrous silicon dioxide, pineapple flavor, banana flavor, tartrazine lake (E 102).

Pharmaceutical form. Powder for oral suspension.

Main physicochemical characteristics: free-flowing powder, from almost white to yellow in color, with a characteristic odor. After reconstitution according to the instructions for medical use, a yellow-colored suspension is formed.

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. In vitro, it demonstrates significant bactericidal activity against a broad spectrum of Gram-positive and Gram-negative microorganisms.

Clinically effective in the treatment of infections caused by commonly encountered 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 the presence of food does not significantly affect absorption, cefixime can be administered independently of food intake. Maximum serum concentrations after administration of recommended doses in adults or children range from 1.5 to 3 mcg/mL. With repeated dosing, slight accumulation of cefixime may occur.

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 isolated from human serum or urine.

Excretion. Cefixime is excreted primarily in unchanged form in the urine. The predominant mechanism is glomerular filtration.

There are no data on the excretion 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 causative agent to other commonly used antibiotics, or in case of risk of treatment inefficacy;
• infections of the lower respiratory tract (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 pathogenic microorganisms most commonly encountered, 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 drug; hypersensitivity to penicillins; porphyria.

Interaction with other medicinal products and other forms of interactions.

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.

Salicylic acid increases 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. 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 bioavailability, but clinical interaction has not been established.

Potentially, as with other antibiotics, use of the drug may lead to reduced efficacy of combined oral contraceptives.

Antacids containing magnesium or aluminium hydroxide delay absorption of the drug.

As with other cephalosporins, prolonged prothrombin time has been observed in some patients; therefore, caution is advised in patients receiving anticoagulant therapy.

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

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

Special precautions for use.

Beta-lactams, including cefixime, may increase the risk of encephalopathy (which may include seizures, confusion, impaired consciousness, and motor disturbances) in patients, particularly 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 immediately and appropriate treatment initiated.

Before initiating cefixime therapy, patients' medical history should be carefully evaluated for hypersensitivity reactions to penicillins, cephalosporins, or other drugs.

Cefixime should be used with caution in patients with a history of allergic reactions to penicillins. Cross-allergic reactions between penicillins and cephalosporins have been demonstrated both in vivo (in the human body) and in vitro. Such cases are rare but may occur in an anaphylactic pattern, especially following parenteral administration.

Antibiotics should be used with caution in patients with a history of any type of hypersensitivity reaction, particularly following drug administration. If an allergic reaction occurs, the drug should be discontinued immediately and appropriate therapy initiated.

Allergic reactions (especially anaphylaxis) associated with the use of beta-lactam antibiotics may be severe and, in rare cases, may be fatal (see section "Adverse reactions").

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 after repeated administration of cephalosporins, including cefixime.

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

Acute renal failure.

As with other cephalosporins, cefixime may lead to acute renal failure, with tubulointerstitial nephritis being the primary pathological condition. If acute renal failure occurs, cefixime should be discontinued and appropriate therapy and/or measures initiated.

Renal impairment.

Dosage adjustment is required for patients with severe renal impairment and for patients undergoing hemodialysis or peritoneal dialysis (see section "Dosage and administration").

Caution should be exercised when prescribing the drug to patients with a history of bleeding disorders, gastrointestinal disorders (particularly ulcerative colitis, regional enteritis, or antibiotic-associated colitis), or hepatic dysfunction.

The safety of cefixime use in premature 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 pseudomembranous colitis associated with antibiotic use, discontinuation of the drug may be sufficient. If colitis symptoms do not improve after discontinuation, oral vancomycin — the drug of choice for pseudomembranous colitis — should be administered.

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

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

During treatment, a positive direct Coombs' test and false-positive urine glucose tests may occur.

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

Important information about excipients

5 mL of reconstituted suspension contains 2.5 g of sucrose. Use with caution in patients with diabetes mellitus. The product should not be administered to patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency. This product 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.

Reproductive studies in mice and rats receiving doses nearly 400 times higher than the human dose showed no adverse effects on fertility or fetal development 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 adequate data on the use of cefixime during pregnancy. Cefixime crosses the placenta.

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

Effect on ability to drive and operate machinery.

Patients who experience central nervous system adverse reactions (e.g., dizziness, impaired consciousness, motor disturbances) while taking the drug should refrain from driving or operating machinery.

Method of Administration and Dosage

Food intake does not affect the absorption of cefixime. The usual duration of treatment is 7 days; if necessary, up to 14 days. For treatment of uncomplicated cystitis, the duration of treatment 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 and 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 recommended adult dose. Renal function should be monitored and the dose adjusted in cases of severe renal impairment (see "Renal impairment").

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 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.

Method of Suspension Preparation

For oral use only.

Before preparation, shake the bottle to loosen the powder. Add boiled, cooled water up to the mark on the bottle; add additional water up to the mark if necessary. The reconstituted suspension must be shaken well before each use.

Children

The drug is indicated for use 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 population.

Overdose

There is a risk of encephalopathy when beta-lactam antibiotics, including cefixime, are used, particularly in cases of overdose and renal impairment. Adverse reactions observed with doses up to 2 g in healthy volunteers were consistent with those seen at recommended doses.

Symptoms: intensification of adverse reactions.

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

Adverse Reactions

When cephalosporins are used, gastrointestinal disturbances are most commonly observed, while hypersensitivity reactions occur less frequently.

Hypersensitivity reactions are more commonly observed in patients who have previously experienced such reactions, as well as in patients with a history of allergies, hay fever, urticaria, or bronchial asthma with an allergic component.

The following adverse reactions have been reported rarely during the use of cefixime:

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

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

Hepatobiliary disorders: jaundice, hepatitis, cholestasis.

Infections and infestations: pseudomembranous colitis.

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

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

Nervous system disorders: headache, dizziness, dysphoria; cases of convulsions have been reported with cephalosporins, including cefixime (frequency unknown). Beta-lactams, including cefixime, may increase the risk of encephalopathy (which may include convulsions, confusion, impaired consciousness, and movement disorders) in patients, particularly in cases of overdose or renal impairment (frequency unknown).

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 disorders: anaphylactic reaction, serum sickness-like reactions, drug fever, arthralgia.

Skin and subcutaneous tissue disorders: urticaria, skin rashes, pruritus, fever, facial swelling, angioneurotic edema, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

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

General disorders and administration site conditions: weakness, fatigue, increased sweating, mucosal inflammation.

*Diarrhea is usually associated with higher doses of the drug. Cases of moderate to severe diarrhea have been reported. If severe diarrhea occurs, cefixime should be discontinued.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is of great importance. It allows continuous 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 Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging. Keep out of reach of children. The reconstituted suspension should be stored in a refrigerator at 2–8 °C for up to 14 days.

Packaging.

1 vial containing powder for the preparation of 100 ml of suspension. Each vial with a measuring cup in a cardboard package.

Prescription status.

Prescription only.

Manufacturer.

Sens Laboratories Pvt. Ltd.

Manufacturer's address and location of its business operations.

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