Instructions Cefinac film-coated tablets 400 mg blister No. 10
Composition
active ingredient: cefixime;
1 film-coated tablet contains cefixime trihydrate equivalent to cefixime 200 mg or 400 mg;
excipients: microcrystalline cellulose (PH 102), calcium hydrogen phosphate dihydrate, pregelatinized starch, magnesium stearate; film coating Opadry White 03G58632: hypromellose, titanium dioxide (E 171), macrogol 3350, triacetin.
Dosage form
Film-coated tablets.
Main physicochemical properties:
200 mg tablets: round, biconvex, film-coated tablets, white to off-white, embossed with “A 11” on one side and plain on the other;
400 mg tablets: oblong, film-coated tablets from white to almost white, with a break line on both sides, embossed with "A" and "10" on one side and plain on the other.
Pharmacotherapeutic group
Antibacterials for systemic use. Other β-lactam antibiotics. Third-generation cephalosporins. ATX code J01D D08.
Pharmacological properties
Pharmacodynamics
Cefixime is a third-generation cephalosporin antibiotic for internal use. In vitro, it exhibits significant bactericidal activity against a wide range of gram-positive and gram-negative microorganisms.
Clinically effective in the treatment of infections caused by the most common pathogens, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase positive and negative), Moraxella (Branhamella) catarrhalis (beta-lactamase positive and negative) and Enterobacter species. 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
The absolute bioavailability of cefixime after oral administration is 22-54%. Since the presence of food does not significantly affect absorption, cefixime can be administered regardless of food intake.
In vitro studies have shown that serum or urine concentrations of 1 μg/mL or greater have been considered adequate for most common pathogens against which cefixime is active. Peak serum levels after administration of recommended doses for adults or children range from 1.5 to 3 μg/mL. There is little or no accumulation of cefixime with repeated administration.
The pharmacokinetics of cefixime were compared in healthy elderly subjects (aged > 64 years) and young volunteers (aged 11–35 years) after administration of 400 mg cefixime once daily for 5 days. The mean maximum concentration (Cmax) and area under the pharmacokinetic curve (AUC) were slightly higher in elderly subjects. Elderly subjects can be given the same doses as adults.
Cefixime is excreted mainly unchanged in the urine. The predominant mechanism is glomerular filtration. Metabolites of cefixime have not been isolated from human serum or urine.
Serum protein binding is well characterized for human and animal serum. Cefixime is almost completely bound to the albumin fraction, with a mean free fraction of approximately 30%. Protein binding of cefixime is dependent only on human serum concentration at very high concentrations not observed after clinical dosing.
The transfer of 14C-labeled cefixime from lactating rats to their offspring via breast milk was quantitatively small (approximately 1.5% of the maternal cefixime content in the offspring). There is no data on the penetration of cefixime into breast milk. Penetration of cefixime across the placenta was negligible in pregnant rats treated with labeled cefixime.
Indication
Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:
upper respiratory tract infections (including otitis media, sinusitis, pharyngitis, tonsillitis of bacterial etiology), in case of known or suspected resistance of the pathogen to other commonly used antibiotics, or in case of risk of ineffectiveness of their use;
lower respiratory tract infections (including bronchitis);
urinary tract infections (including cystitis, cystourethritis, uncomplicated pyelonephritis).
Contraindication
Hypersensitivity to cefixime or to any of the excipients, other cephalosporins or penicillins (see section "Special warnings and precautions for use"). Porphyria.
Interaction with other medicinal products and other types of interactions
Anticoagulants
As with other cephalosporins, increases in prothrombin time have been reported in some patients, therefore caution should be exercised in patients receiving anticoagulant therapy.
Other forms of interactions
During treatment with cefixime, a false-positive reaction for glucose in the urine may occur when using copper sulfate tablets, Benedict's or Fehling's solutions. It is recommended to use a glucose oxidase test to determine glucose in the urine.
Cephalosporin antibiotics may cause a false-positive direct Coombs test. Therefore, it should be borne in mind that a positive Coombs test may be due to the use of this medicinal product.
Application features
Encephalopathy
Beta-lactams, including cefixime, increase the risk of encephalopathy (which may include convulsions, confusion, impaired consciousness, movement disorders) in patients, especially in cases of overdose and renal failure.
Severe skin reactions
Severe cutaneous adverse reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS syndrome) and acute generalized exanthematous pustulosis (AGEP) have been reported in some patients with cefixime. Patients should be informed of the signs and symptoms of serious skin reactions and such patients 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 prescribed with caution to patients with hypersensitivity to other drugs.
Hypersensitivity to penicillins
As with other cephalosporins, cefixime should be used with caution in patients with hypersensitivity to penicillins, as there is some evidence of partial cross-allergy between penicillins and cephalosporins.
Serious reactions (including anaphylaxis) have been reported in patients with both classes of drugs. If an allergic reaction occurs, the drug should be discontinued immediately and appropriate treatment should be initiated.
Hemolytic anemia
Cases of hemolytic anemia, including severe cases with fatal outcome, have been described following the use of cephalosporins. Hemolytic anemia has also been reported following repeated use of cephalosporins (including cefixime).
Acute renal failure
As with other cephalosporins, cefixime may cause 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 measures should be taken.
Kidney failure
Cefixime should be used with caution in patients with significant renal impairment (see section "Method of administration and dosage").
Use in pediatrics
The safety of cefixime in premature or newborn infants has not been established (see section "Special warnings and precautions for use").
Antibiotic-associated colitis
Prolonged use of antibacterial drugs can disrupt the normal intestinal flora, which can lead to overgrowth of Clostridium difficile. Studies suggest that a toxin produced by Clostridium difficile is the 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), so it is important to consider this diagnosis in patients with antibiotic-associated diarrhea. Symptoms of pseudomembranous colitis may occur during or after discontinuation of antibiotic therapy.
Treatment of pseudomembranous colitis should include sigmoidoscopy, appropriate bacteriological studies, fluids, electrolytes, and protein solutions. If symptoms of colitis do not improve after discontinuation of the drug, oral vancomycin should be administered, which is the antibiotic of choice in the case of pseudomembranous colitis caused by C. difficile. Other causes of colitis should be excluded.
Use during pregnancy or breastfeeding
In reproductive studies in animals given doses approximately 400 times the human dose, no effect on fertility or foetal harm was observed due to cefixime. In animals given doses up to 4 times the human dose, there was no evidence of teratogenic effects; a high incidence of abortions and maternal mortality was observed, which is an expected consequence of the known sensitivity of animals to changes in the gut microbiota caused by antibiotics.
There are no data on the use of the drug during pregnancy. Cefixime crosses the placenta.
The drug should not be used during pregnancy or breastfeeding, except when prescribed by a doctor in case of urgent need.
Ability to influence reaction speed when driving vehicles or other mechanisms
In case of adverse reactions such as encephalopathy (which may include seizures, confusion, impaired consciousness, movement disorders), the patient should avoid driving or operating other machinery.
Method of administration and doses
Food intake does not affect the absorption of cefixime. Usually the course 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: The recommended dose for adults is 200-400 mg per day, depending on the severity of the infection, given as a single dose or in two divided doses.
Elderly patients. The drug is prescribed in the recommended adult dose. Kidney function should be monitored and the dose adjusted in severe renal failure.
Children weighing more than 50 kg or aged 10 years and over. Treatment is carried out according to the recommended dose for an adult (200 - 400 mg per day depending on the severity of the infection).
The safety and effectiveness of cefixime have not been established in children under 6 months of age.
Dosage in renal failure. Cefixime can be used in cases of impaired renal function. For patients with creatinine clearance of 20 ml/min or higher, the usual dose and dosing regimen should be prescribed. For patients with creatinine clearance below 20 ml/min, it is not recommended to exceed a dose of 200 mg once daily. This also applies to patients on continuous ambulatory peritoneal dialysis or hemodialysis.
Children
Children under 10 years of age are recommended to use the drug in a different dosage form.
Overdose
There is a risk of encephalopathy with the use of beta-lactam antibiotics, including cefixime, especially in cases of overdose or renal impairment. Data from studies have shown that cefixime has the same safety profile at doses up to 2 g per day as at the recommended therapeutic doses.
Dialysis only slightly helps to remove cefixime from the body. There is no specific antidote. General supportive therapy is recommended.
Side effects
Adverse reactions caused by cefixime are minor and occur rarely.
From the blood and lymphatic system: eosinophilia, hypereosinophilia, agranulocytosis, leukopenia, neutropenia, granulocytopenia, hemolytic anemia, thrombocytopenia, thrombocytosis.
Gastrointestinal: abdominal pain, diarrhea*, dyspepsia, nausea, vomiting, flatulence.
Liver: jaundice.
Infections and infestations: pseudomembranous colitis, vaginitis.
Laboratory indicators: increased levels of transaminases (AST, ALT), bilirubin, urea, and creatinine in blood serum.
Nervous system: headache, dizziness, cases of convulsions have been reported with the use of cephalosporins, including cefixime (frequency unknown).
Beta-lactams, including cefixime, increase the risk of encephalopathy (which may include seizures, confusion, impaired consciousness, movement disorders) in patients, especially in cases of overdose and renal failure (frequency unknown)**.
Respiratory system: dyspnea
Renal and urinary disorders: acute renal failure, including tubulointerstitial nephritis (see section "Special warnings and precautions for use").
Immune system disorders: anaphylactic reactions, angioedema, 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 warnings and precautions for use").
General disorders: fever, arthralgia, facial edema, genital itching.
*Diarrhea is usually associated with higher doses. Cases of diarrhea (moderate to severe) have been reported, warranting discontinuation of therapy. Cefixime should be discontinued if severe diarrhea occurs.
**Cannot be estimated based on available data.
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 30 °C in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister; 1 blister in a cardboard box.
Vacation category
According to the recipe.
Producer
Nectar Life Sciences Limited-Unit VI.
Location of the manufacturer and address of its place of business
Bhatolikalan Village, Near Jharmajri, E.P.I.P., P.V. Barotiwala, Tehsil Baddi, District Solan, Himachal Pradesh, 174103, India.
