Cefinac

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEFINAK® (CEFINAK®)

Composition:

Active substance: cefixime;

5 ml of suspension contains cefixime trihydrate equivalent to 100 mg of cefixime;

Excipients: sucrose, xanthan gum, sodium benzoate (E 211), colloidal anhydrous silicon dioxide, strawberry-guarana flavor 586997 AR0551.

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties:

for the dry powder: granular powder from almost white to light yellow in color with a characteristic odor;

for the reconstituted suspension: light yellow suspension with a characteristic odor.

Pharmacotherapeutic group.

Antibacterials for systemic use. Other β-lactam antibiotics. Third-generation cephalosporins. ATC code 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.

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 (β-lactamase-positive and negative), and Enterobacter species. Exhibits high stability in the presence of β-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% to 54%. Since the presence of food does not significantly affect absorption, cefixime can be administered regardless of food intake. Peak serum concentrations after administration of recommended doses in adults or children range from 1.5 to 3 μg/mL. With repeated dosing, there is minimal or virtually no accumulation of cefixime.

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

Metabolism. Metabolites of cefixime have not been isolated from human serum or urine.

Excretion. Cefixime is primarily excreted unchanged in 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:

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

Contraindications.

Hypersensitivity to cefixime or to other components of the drug, other cephalosporins or penicillins (see section "Special precautions"). Porphyria.

Interaction with other medicinal products and other forms of interaction.

Anticoagulants

As with other cephalosporins, prolonged prothrombin time has been reported 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, prolongation of prothrombin time with or without clinical signs of bleeding may occur.

Other forms of interactions

During treatment with cefixime, false-positive glucose in urine reactions 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 a false-positive direct Coombs' test result. Therefore, it should be borne in mind that a positive Coombs' test result may be due to administration 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, and movement disorders) in patients, particularly in cases of overdose and renal impairment.

Severe skin reactions

Severe cutaneous adverse reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP) have been reported in some patients receiving cefixime. Patients should be informed about the signs and symptoms of serious skin reactions and should be closely monitored. Treatment should be discontinued at the first appearance of skin rash, mucosal lesions, or any other signs of skin hypersensitivity.

The drug should be administered with caution to patients with known hypersensitivity to other drugs.

Hypersensitivity to penicillins

As with other cephalosporins, cefixime should be used with caution in patients with a history of penicillin hypersensitivity, as there is some evidence of partial cross-allergenicity between penicillins and cephalosporins.

Serious reactions (including anaphylaxis) have been observed with both drug classes. If an allergic reaction occurs, the drug should be discontinued immediately and appropriate therapy initiated.

Hemolytic anemia

Cases of hemolytic anemia, including severe cases with fatal outcomes, have been reported following the use of cephalosporins. Hemolytic anemia has also been reported after re-administration of cephalosporins (including cefixime).

Acute renal failure

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

Renal impairment

Cefixime should be used with caution in patients with significant renal dysfunction (see section "Dosage and administration").

Pediatric use

The safety of cefixime in premature infants or neonates has not been established (see section "Special precautions for use").

Antibiotic-associated colitis

Prolonged use of antibacterial agents may disrupt the normal intestinal flora, leading to overgrowth of Clostridium difficile. Studies indicate that the toxin produced by C. difficile is a primary cause of antibiotic-associated diarrhea. Pseudomembranous colitis has been associated with the use of broad-spectrum antibiotics (including macrolides, semisynthetic penicillins, lincosamides, and cephalosporins); therefore, this diagnosis should be considered in patients who develop diarrhea during or after antibiotic therapy.

Symptoms of pseudomembranous colitis may occur during or after discontinuation of antibiotic treatment.

Treatment of pseudomembranous colitis should include sigmoidoscopy, appropriate bacteriological testing, and administration of fluids, electrolytes, and protein solutions. If colitis symptoms do not improve after discontinuation of the drug, oral vancomycin should be administered. Vancomycin is the drug of choice for pseudomembranous colitis caused by C. difficile. Other causes of colitis must be ruled out.

Important information about certain excipients.

5 ml of reconstituted suspension contains 2.338 g of sucrose. Use with caution in patients with diabetes mellitus. The drug 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 animals administered doses nearly 400 times the human dose showed no adverse effects on fertility or fetal development due to cefixime. In animal studies at doses up to 4 times the human dose, no evidence of teratogenicity was observed. However, a high incidence of abortions and maternal mortality was noted, which is an expected consequence of the known sensitivity of animals to antibiotic-induced changes in intestinal flora.

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

The drug should not be used during pregnancy or breastfeeding except when clearly needed and prescribed by a physician.

Ability to affect driving performance and operating machinery.

If adverse reactions such as encephalopathy (which may include seizures, confusion, impaired consciousness, and movement disorders) occur, patients should avoid 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, it may be extended 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 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: The drug should be administered at the standard adult dose. Renal function should be monitored and dosage adjusted in cases of severe renal impairment (see "Dosage in Renal Impairment").

In Renal Impairment: Cefixime can be used.

For patients with a creatinine clearance of 20 mL/min or higher, the standard 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, invert and shake the bottle to loosen the powder, then add boiled cooled water (see table).

After reconstitution, store the suspension in the refrigerator for 14 days. Do not freeze. The vial should be kept tightly closed.

Before each administration, shake the vial well to thoroughly mix the reconstituted suspension.

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 developing encephalopathy when using beta-lactam antibiotics, including cefixime, particularly in cases of overdose or impaired renal function.

Study data have shown that cefixime has a similar safety profile at doses up to 2 g per day as with recommended therapeutic doses. Dialysis contributes only minimally to the elimination of cefixime from the body.

There is no specific antidote. General supportive therapy is recommended.

Side effects

Side effects caused by cefixime are mild and occur rarely.

Blood and lymphatic system disorders: eosinophilia, hyper-eosinophilia, agranulocytosis, leukopenia, neutropenia, granulocytopenia, hemolytic anemia, thrombocytopenia, thrombocytosis.

Gastrointestinal disorders: abdominal pain, diarrhea*, dyspepsia, nausea, vomiting, flatulence.

Hepatic disorders: jaundice.

Infections and infestations: pseudomembranous colitis, vaginitis.

Laboratory findings: increased levels of transaminases (AST, ALT), bilirubin, urea, and creatinine in blood serum.

Nervous system disorders: headache, dizziness; 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, particularly in cases of overdose and renal impairment (frequency unknown)**.

Respiratory system disorders: dyspnea.

Renal and urinary system disorders: acute renal failure, including tubulointerstitial nephritis (see section "Special precautions for use").

Immune system disorders: anaphylactic reactions, angioneurotic edema, serum sickness-like reactions.

Skin and subcutaneous tissue disorders: drug rash with eosinophilia and systemic symptoms (DRESS syndrome), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, skin rashes, pruritus, acute generalized exanthematous pustulosis (AGEP) (see section "Special precautions for use").

General disorders: fever, arthralgia, facial swelling, genital pruritus.

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

**Cannot be estimated from available data.

Reporting suspected adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the drug. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life

For dry powder (prior to reconstitution) – 3 years.

For prepared suspension (after reconstitution) – 14 days.

Storage conditions

For dry powder (prior to reconstitution)

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

Keep out of reach of children.

For prepared suspension (after reconstitution)

Store in a refrigerator (do not freeze).

Keep out of reach of children.

Packaging

1 vial of powder for preparation of 50 mL of suspension or 1 vial of powder for preparation of 100 mL of suspension. Each vial with a measuring cup and a measuring spoon, packed in a cardboard box.

Prescription status – Prescription only.

Manufacturer

Nectar Lifesciences Limited - Unit VI.

Manufacturer's address and location of operations

Village Bhatolikalan, near Jharmajri, EPIP, P.O. Barotiwala, Tehsil Baddi, District Solan, Himachal Pradesh, 174103, India.