Sorcef

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

Composition:

Active substance: cefixime;

One film-coated tablet contains 400 mg of cefixime (as cefixime trihydrate 447.630 mg);

Excipients: gelatin; calcium hydrogen phosphate dihydrate; corn starch; pregelatinized starch; magnesium stearate; sodium lauryl sulfate; microcrystalline cellulose; hypromellose; macrogol 4000; titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, biconvex, film-coated tablets, white to slightly cream-colored, with a break line on one side.

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 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, group D streptococci) 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. Maximum serum concentrations after administration of recommended doses in adults or children range from 1.5 to 3 mcg/mL. With repeated dosing, there is either slight accumulation of cefixime or practically no accumulation at all.

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 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 and inflammatory diseases caused by microorganisms sensitive to the drug:

• upper respiratory tract infections (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 treatment inefficacy;
• 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 drug; increased sensitivity to penicillins; porphyria.

Interaction with other medicinal products and other forms of interaction.

Tubular secretion blockers (allopurinol, probenecid, diuretics, and other tubular secretion blockers) increase the maximum serum concentration of cefixime by slowing renal excretion of cefixime, 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 concomitantly 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 has not been 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, false-positive direct Coombs' test reactions and false-positive urine glucose reactions with copper sulfate tablets, Benedict's or Fehling's solutions may occur. Glucose in urine should be determined using a glucose oxidase test.

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 and appropriate treatment initiated.

Cefixime should be administered with caution in patients with a history of hypersensitivity reactions to other drugs.

Severe reactions (including anaphylactic shock) to cefixime have been reported. If an allergic reaction to cefixime occurs, the drug should be discontinued immediately 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 renal failure, including tubulointerstitial nephritis as the underlying pathological condition. If acute renal failure occurs, cefixime should be discontinued and appropriate therapy and/or interventions initiated.
Caution should be exercised when prescribing the drug in patients with a history of bleeding disorders, gastrointestinal diseases, particularly ulcerative colitis, regional enteritis, or antibiotic-associated colitis, as well as in patients with hepatic dysfunction.

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

Treatment with broad-spectrum antibiotics may disrupt normal intestinal flora, potentially leading to overgrowth of Clostridium difficile, which produces toxins and is a major 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, 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 replacement of 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 loop diuretics (furosemide, ethacrynic acid) in high doses, 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 tests may occur.

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

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 adverse effects on fertility or fetal abnormalities attributable 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 only under a physician's supervision.

Ability to affect reaction speed when driving or operating machinery.

No effect. However, patients who experience central nervous system adverse reactions (e.g., dizziness) while taking Sorcef® should refrain from driving or operating machinery during treatment.

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. In the treatment of uncomplicated cystitis, the course of treatment is 3 days.

Adults and children aged 12 years and older with body weight over 50 kg: the recommended dose is 400 mg (one tablet) once daily or 200 mg (half a tablet) 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 case 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, the usual dose and dosing regimen should be administered. For patients with creatinine clearance below 20 mL/min, the dose should not exceed 200 mg (half a tablet) once daily. This also applies to patients undergoing continuous ambulatory peritoneal dialysis or hemodialysis.

Children.

Cefixime is not recommended for children under 12 years of age in tablet form; another pharmaceutical formulation should be used.

Overdose.

Cases of overdose have not been reported. Adverse reactions observed with 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 contributes only minimally to the elimination of cefixime 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 and bile duct disorders: jaundice, hepatitis, cholestasis.

Infections and parasitic disorders: 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 therapy 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).

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-induced vaginitis.

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

*Diarrhea, usually associated with higher doses of the drug. Cases of mild to severe diarrhea have been reported; in such cases, discontinuation of therapy may be 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 at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

Film-coated tablets, 400 mg.

5 tablets per blister, 1 or 2 blisters per cardboard box.

7 tablets per blister; 1 blister per cardboard box.

Prescription category.

Prescription only.

Manufacturer.

ALKALOID AD Skopje.

Manufacturer's address and place of business.

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