OPTICEF

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

Composition:

Active substance: cefixime;

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

Excipients: microcrystalline cellulose (type 101), calcium hydrogen phosphate dihydrate, pregelatinized starch, microcrystalline cellulose (type 102), magnesium stearate;

Film-coating Opadry Y-1-7000 white: hypromellose, macrogol/PEG 400, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, biconvex film-coated tablets of white to light cream color with a score line on one side.

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. 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.

Pharmacokinetics.

Absorption. Absolute bioavailability after oral administration of cefixime ranges from 22% to 54%. Since food does not significantly affect absorption, cefixime can be administered independently of food intake. Peak serum concentrations following 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 average free fraction being 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 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, 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; 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 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 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 has not been established.

Potentially, similar to other antibiotics, reduced effectiveness of combined oral contraceptives may occur during treatment with the drug.

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

As with other cephalosporins, increased prothrombin time has been observed in some patients; therefore, caution is recommended for 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 glucose in urine reactions 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.

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

Prior to initiating therapy with cefixime, patients should be carefully questioned regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.

Cefixime should be administered with caution to 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 organism) and in vitro. Although such cases are rare, they may occur in an anaphylactic manner, particularly after parenteral administration.

Antibiotics should be used cautiously in patients with a history of any type of hypersensitivity reaction, especially 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 during cephalosporin therapy. Hemolytic anemia has also been reported after repeated administration of cephalosporins, including cefixime.

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

Blood parameters should be monitored during prolonged treatment (more than 10 days).

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 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 in patients with 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—considered the drug of choice for pseudomembranous colitis—should be administered.

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

When cefixime is used concomitantly with aminoglycosides, polymyxin B, colistin, or loop diuretics (furosemide, ethacrynic acid) at high doses, 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 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.

Reproductive function studies in mice and rats receiving doses nearly 400 times higher than the human dose showed no evidence of 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 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.

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

Dosage and Administration

Food intake does not affect the absorption of cefixime. The usual duration of treatment is 7 days, and if necessary, up to 14 days. For the treatment of uncomplicated cystitis, the treatment course 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 dosage 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 usual dose and dosing regimen are recommended. 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. An alternative dosage form should be used for this age group.

Overdose.

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

Adverse reactions observed following administration of doses up to 2 g in healthy volunteers did not differ from those seen in patients receiving the 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 spasms, abdominal pain, diarrhea*, dyspepsia, nausea, vomiting, flatulence, dysbacteriosis, oral mucosal candidiasis, stomatitis, glossitis.

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

Infections and parasitic disorders: 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; 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, movement disorders, and impaired consciousness) 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 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 after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical 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.

3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

7 tablets per blister, 1 or 2 blisters per carton.

Prescription status.

Prescription only.

Manufacturer.

Limited Liability Company "Agrofarm".

Limited Liability Company "Natur+".

Manufacturer's address and location of business activity.

113-A Centralna Street, Irpin, Kyiv region, 08200, Ukraine

3 Tarasa Shevchenka Street, Irpin, Kyiv region, 08200, Ukraine