Opticef

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

Composition:

Active substance: cefixime;

5 ml of the preparation contain cefixime 100 mg (as cefixime trihydrate – 111.9 mg);

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

Pharmaceutical form. Granules for oral suspension.

Main physicochemical properties:

Granules: granules from almost white to light yellow in color;

Suspension: viscous liquid from almost white to light yellow in color.

Pharmacotherapeutic group. Antibacterials for systemic use.
Beta-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 (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 regardless of food intake. The maximum serum concentration after administration of recommended doses in adults or children ranges 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 average free fraction being approximately 30%.

Metabolism. Cefixime metabolites have not been isolated from human serum or urine.

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

There are no data regarding the penetration of cefixime into breast milk.

Clinical characteristics.

Indications.

Infectious and 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 ineffective treatment;
• 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 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; hypersensitivity to penicillins; porphyria.

Interaction with other medicinal products and other forms of interaction.

Tubular secretion blockers (allopurinol, probenecid, diuretics) 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 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, reduced effectiveness of combined oral contraceptives may occur during treatment with this drug.

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 may occur.

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. Glucose oxidase test is 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 movement disorders) in patients, particularly in cases of overdose and renal impairment.

Severe skin 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. If severe skin adverse reactions occur, cefixime should be discontinued immediately and appropriate therapy initiated.

Prior to administration of cefixime, a careful patient history regarding hypersensitivity reactions to penicillins, cephalosporins, or other drugs should be obtained.

Cefixime should be administered with caution to patients with a history of allergic reactions to penicillins. Cross-sensitivity between penicillins and cephalosporins has been demonstrated both in vivo (in the human body) and in vitro. Although such cases are rare, they may occur in an anaphylactic manner, especially following parenteral administration.

Antibiotics should be used cautiously in patients with a history of any type of hypersensitivity reaction, particularly to drugs. If an allergic reaction 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 with cephalosporin therapy. Hemolytic anemia has also been reported following re-administration of cephalosporins (including cefixime).

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

In patients receiving prolonged treatment (more than 10 days), blood parameters should be monitored regularly.

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

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 interventions 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 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 the development of pseudomembranous colitis. In mild cases of pseudomembranous colitis induced by antibiotics, discontinuation of the drug may be sufficient. If symptoms of colitis do not resolve after discontinuation, oral vancomycin should be administered, as it is the antibiotic of choice for pseudomembranous colitis.

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.

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.

For infections caused by group A beta-hemolytic streptococci, the treatment course should last at least 10 days to prevent acute rheumatic fever.

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

Cephalosporins increase alcohol toxicity; therefore, consumption of alcoholic beverages is 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 after taking the medication.

Use during pregnancy or breastfeeding.

Reproductive studies in mice and rats administered 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 only under medical supervision.

Ability to influence reaction speed when driving or operating machinery.

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

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 (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 standard 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 creatinine clearance of 20 mL/min or higher, the standard dose and dosing regimen should be used. 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.

For 60 mL of suspension (100 mg/5 mL): shake the bottle several times before reconstitution; add 40 mL of cooled boiled water at room temperature in two portions, and shake well until a homogeneous suspension is formed.

For 100 mL of suspension (100 mg/5 mL): shake the bottle several times before reconstitution; add 66 mL of cooled boiled water at room temperature in two portions, and shake well until a homogeneous suspension is formed.

The reconstituted suspension should be shaken well before each use. The suspension should be administered using a dosing spoon.

Pediatric use.

The drug can be administered to children aged 6 months and older. The 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.

There is a risk of encephalopathy when beta-lactam antibiotics, including cefixime, are used, especially in cases of overdose and renal impairment.

Adverse reactions observed with doses up to 2 g in healthy volunteers were no different 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 only slightly enhances 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 prothrombin and thrombin time, purpura.

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

Hepatobiliary and biliary disorders: jaundice, hepatitis, cholestasis.

Infections and infestations: pseudomembranous colitis.

Laboratory findings: 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; convulsions have been reported during treatment with cephalosporins, including cefixime (frequency unknown).

Beta-lactams, including cefixime, may increase the risk of encephalopathy (which may include convulsions, confusion, altered consciousness, and movement disorders) in patients, especially 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 main 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, acute generalized exanthematous pustulosis (AGEP) (see section "Special precautions").

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

General disorders: 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 adverse reactions following marketing authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. 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 Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Reconstituted suspension should be stored for up to 14 days at a temperature not exceeding 25 °C.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

32 g or 53 g of granules in a brown glass bottle, 1 bottle with a measuring spoon in a carton.

Prescription status.

Prescription only.

Manufacturer.

Limited Liability Company "Agrofarm".

Limited Liability Company "Natur+".

Manufacturer's address and place of business.

Ukraine, 08200, Kyiv region, city of Irpin, Central Street, 113-A.

Ukraine, 08200, Kyiv region, city of Irpin, Taras Shevchenko Street, 3.