Sorcef

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

Composition:

Active substance: cefixime;

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

Excipients: sodium benzoate (E 211), sucrose, xanthan gum, orange flavor.

Pharmaceutical form. Granules for oral suspension.

Main physicochemical properties:

Granules: nearly white to pale yellow granules and crystals with a pleasant orange odor;

Suspension: viscous liquid ranging from nearly white to pale yellow in color with a pleasant orange odor.

Pharmacotherapeutic group. Antibacterials for systemic use. Beta-lactam antibiotics. Third-generation cephalosporins. ATC code J01DD08.

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 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% to 54%. Since the presence of food does not significantly affect absorption, cefixime can be administered independently 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 dosing, minimal or no accumulation of cefixime occurs.

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 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 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 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 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.

Contraindications.

Confirmed hypersensitivity to cephalosporin antibiotics or to other components of the drug; increased sensitivity to penicillins; porphyria.

Interaction with other medicinal products and other types of interactions.

Tubular secretion blockers (allopurinol, probenecid, diuretics, etc.) 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 increase its plasma concentration; therefore, monitoring of carbamazepine plasma levels is advisable.

When cefixime is used in combination with potentially nephrotoxic substances (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 is not established.

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

As with other cephalosporins, prolonged 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 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 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 detection of glucose in urine, a glucose oxidase test is recommended.

Special precautions for use.

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 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.

Cefixime should be administered with caution to patients who have previously experienced hypersensitivity reactions to other drugs. Severe reactions (including anaphylactic shock) to cefixime have been reported. If an allergic reaction to cefixime develops, the drug should be discontinued and appropriate therapy initiated.

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 impairment (see "Dosage in renal impairment").

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

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 hepatic impairment.

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

Treatment with broad-spectrum antibiotics may disrupt the normal intestinal microflora, leading to overgrowth of Clostridium difficile, which produces toxins and is the primary cause of antibiotic-associated diarrhea. Pseudomembranous colitis has been associated with the use of broad-spectrum antibiotics (including macrolides, semi-synthetic penicillins, lincosamides, and cephalosporins). Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after antibiotic therapy. Symptoms of pseudomembranous colitis may develop during or after discontinuation of antibiotic treatment.

Treatment of pseudomembranous colitis should include sigmoidoscopy, appropriate bacteriological investigations, and rehydration with fluids, electrolytes, and proteins. If symptoms do not improve after discontinuation of the drug or become severe, oral vancomycin should be administered. Vancomycin is the drug of choice for treating antibiotic-associated pseudomembranous colitis caused by C. difficile. Other potential causes of colitis should be excluded.

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 use of cefixime, hematopoietic function should be evaluated.

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

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

Important information about some components of the medicinal product.

5 ml of reconstituted suspension contains 2.517 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. This medicinal product may be harmful to teeth. It is recommended to rinse the mouth with water after administration; children should drink sufficient water afterwards.

Use during pregnancy or breastfeeding.

In reproductive studies in mice and rats, administration of doses nearly 400 times higher than the human dose did not reveal any 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 was noted, which is an expected consequence of the known sensitivity of rabbits to antibiotic-induced changes in intestinal microflora.

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

The medicinal product should not be used during pregnancy or breastfeeding except in cases of extreme necessity and only under a physician's prescription.

Ability to affect the speed of reactions while driving or operating machinery.

Patients who experience adverse reactions from the central nervous system (e.g., dizziness, impaired consciousness, movement disorders) during treatment with Sorcef® should refrain from driving or operating machinery during treatment.

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 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 of 50 kg and above): 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 dosage 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 usual 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.

Method of Suspension Preparation

For oral use only.

For 60 mL of suspension (100 mg/5 mL): shake the bottle several times before reconstitution. Using the measuring cup provided, add 40 mL of purified water in two portions and shake well until a uniform suspension is formed.

For 100 mL of suspension (100 mg/5 mL): shake the bottle several times before reconstitution. Using the measuring cup provided, add 66 mL of purified water in two portions and shake well until a uniform suspension is formed.

The prepared suspension should be shaken well before each use.

The suspension should be dosed using the graduated pipette supplied. The measuring cup is intended only for measuring the amount of water required for reconstitution of the suspension.

A plastic graduated pipette provided with the product should be used to measure the required volume of suspension.

How to Use the Graduated Pipette:

1. Shake the bottle well before use and remove the cap.
2. Remove the cap from the pipette and insert the pipette into the bottle.
3. Pull the plunger upwards along the barrel until the edge of the barrel aligns with the mark on the plunger corresponding to the required dose.

1. Remove the pipette from the bottle.
2. While holding the pipette vertically, place the tip directly into the mouth, directing it towards the inner cheek.
3. Slowly press the pipette plunger to dispense the medication gradually, avoiding choking. DO NOT inject the medication as a jet stream.
4. Repeat steps 2–6 in the same manner until the entire dose has been administered.
5. After administration, close the bottle with the cap. Disassemble the pipette and thoroughly rinse it with drinking water. Allow the plunger and barrel to air-dry naturally.

Children.

The drug can be administered to 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.

Cases of overdose have not been reported. Adverse reactions observed when the drug was administered at doses up to 2 g in healthy study participants did not differ from those seen in patients receiving the drug at recommended doses.

Symptoms: intensification of adverse reactions.

Treatment: gastric lavage; administer symptomatic and supportive therapy.

There is no specific antidote. Hemodialysis or peritoneal dialysis only slightly enhances the elimination of cefixime from the body.

Side effects.

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 bruising without apparent cause), purpura.

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

Hepatobiliary and biliary tract disorders: jaundice, hepatitis, cholestasis.

Infections and infestations: pseudomembranous colitis.

Laboratory test abnormalities: increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased blood bilirubin, increased blood urea, increased serum creatinine.

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

Nervous system disorders: headache, dizziness, dysphoria, hyperactivity; 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, impaired consciousness, motor disturbances) in patients, particularly in cases of overdose and 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 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 fever, and arthralgia, including rare cases of urticaria 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 pruritus, Candida vulvovaginitis.

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

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

Shelf life.

3 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store granules at a temperature not exceeding 25 °C.

Store the reconstituted suspension for up to 14 days at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

For 60 mL suspension

32 g of granules in a dark glass bottle with an aluminum screw cap with a polyethylene liner and a tamper-evident seal, with a plastic graduated pipette and a measuring cup, in a cardboard box.

For 100 mL suspension

53 g of granules in a dark glass bottle with an aluminum screw cap with a polyethylene liner and a tamper-evident seal, with a plastic graduated pipette and a measuring cup, in a cardboard box.

Prescription category.

Prescription only.

Manufacturer.

ALKALOID AD Skopje.

Manufacturer's address and place of business.

Boulevard of Alexander the Great, 12, Skopje, 1000, Republic of North Macedonia.