Zinnat
Use during pregnancy and breastfeeding
Zinnat® should be used if the expected benefit to the mother outweighs the potential risk to the child.
There is no experimental evidence of embryopathic or teratogenic effects of cefuroxime axetil, but as with other drugs, caution must be exercised when prescribing it in early pregnancy.
Caution must be exercised when prescribing it to nursing mothers, since the drug is detected in breast milk.
Use for renal impairment
Caution should be exercised when prescribing to patients with impaired renal function.
Use in children
Contraindicated in children under 3 months of age (for oral suspension); for tablets - children under 3 years of age (for children from 3 months to 3 years, the drug Zinnat® should be used in the form of a suspension).
special instructions
Caution should be exercised when prescribing the drug to patients with a history of an allergic reaction to beta-lactam antibiotics.
During treatment, it is necessary to monitor renal function, especially in patients receiving the drug in high doses.
During the period of taking Zinnat®, a false positive urine reaction to glucose is possible.
As with other antibiotics, long-term use of Zinnat® can lead to overgrowth of Candida fungi. Long-term use may cause the growth of other resistant microorganisms (Enterococcus and Clostridium difficile), which may require discontinuation of treatment.
Pseudomembranous colitis has been observed with the use of broad-spectrum antibiotics, and the differential diagnosis of pseudomembranous colitis should be considered in patients with severe diarrhea that occurs during or after a course of antibiotic treatment.
The Jarisch-Herxheimer reaction was observed in borreliosis (Lyme disease) when taking the drug Zinnat® and is due to the bactericidal activity of the drug against the causative agent of the disease, the spirochete Borrelia burgdorferi. Patients should be informed that these symptoms are a typical consequence of antibiotic use for this disease.
If the clinical effect is not achieved within 72 hours from the start of treatment, the parenteral course of therapy should be continued.
Before starting step therapy, you should consult available references regarding cefuroxime sodium salt (Zinacef®).
Zinnat® tablets should not be broken or crushed. Therefore, this dosage form is not used to treat patients with swallowing difficulties, incl. small children who cannot swallow a whole tablet.
The sucrose content in the Zinnat® suspension should be taken into account when treating patients with diabetes mellitus.
5 ml of prepared Zinnat® suspension contains 0.25 bread units (XE).
Impact on the ability to drive vehicles and operate machinery
Since cefuroxime axetil may cause dizziness, patients should be warned to take precautions when driving or operating moving machinery.
Zinnat granules for the preparation of suspension for oral administration 125 mg/5 ml No. 1
Name
Zinnat gran.d/prig.susp.d/pr.vn.125mg/5ml in bottle in pack No. 1
Description
White or almost white free-flowing granules. When reconstituted with water, a white or pale yellow suspension is formed with a characteristic fruity odor.
Main active ingredient
Cefuroxime
Release form
Granules
Dosage
125mg/5ml
pharmachologic effect
Pharmacodynamics
Pharmacodynamics Mechanism of action Cefuroxime axetil is hydrolyzed by esterase enzymes into the active antibiotic, cefuroxime. Cefuroxime inhibits bacterial cell wall synthesis after binding to penicillin binding proteins (PBPs). This leads to interruption of the biosynthesis of the cell wall (peptidoglycans), which ultimately leads to lysis and death of the bacterial cell. Mechanism of resistance Bacterial resistance to cefuroxime may be a consequence of one or more of the following mechanisms: - hydrolysis by beta-lactamases; including (but not limited to) extended spectrum beta-lactamases (ESBLs), and AmpC enzymes that can be induced or persistently activated in certain species of aerobic gram-negative bacteria; - reduced affinity of penicillin-binding proteins for cefuroxime; - impermeability of the outer shell, which limits the access of cefuroxime to penicillin-binding proteins in gram-negative bacteria; — mechanisms of bacterial efflux. Microorganisms that have become resistant to other injectable cephalosporins are expected to be resistant to cefuroxime. Depending on the mechanism of resistance, microorganisms with acquired resistance to penicillins may demonstrate reduced sensitivity or resistance to cefuroxime. Cefuroxime axetil breakpoints The minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are given below: European Committee on Antimicrobial Susceptibility Testing. Table of limit values for interpreting MIC values. Version
2
,
2012
; www.eucast.org. Microorganism - Limit Values
mg/l
H — P Enterobacteriaceae1, 2 — ≤8 — >8 Staphylococcus spp. — Note3 — Note3 Streptococcus A, B, C and G — Note4 — Note4 Streptococcus pneumoniae — ≤0.25 — >0.5 Moraxella catarrhalis — ≤0.125 — >4 Haemophilus influenzae — ≤0.125 — >1 Boundary values not related to specific bacterial species1 ND5 ND5 1 Cephalosporin breakpoints for Enterobacteriaceae will detect all clinically relevant resistance mechanisms (including ESBL and plasmid-mediated AmpC). Some strains that produce beta-lactamases are susceptible or intermediately susceptible to 3rd or 4th generation cephalosporins and should be reported as discovered, i.e. The presence or absence of ESBL does not in itself affect the determination of the sensitivity category. In many areas, detection and characterization of ESBL is recommended or mandatory for infection control purposes. 2 Uncomplicated urinary tract infection (cystitis) only (see section “Indications for use”). 3 The conclusion about the sensitivity of staphylococci to cephalosporins is based on sensitivity to methicillin, with the exception of ceftazidime, cefixime and ceftibuten, which do not have borderline values and should not be used for staphylococcal infections. 4 The conclusion about sensitivity to beta-lactams of beta-hemolytic streptococci of groups A, B, C and G is based on sensitivity to penicillin. 5 There is insufficient evidence that the species in question are good targets for drug therapy. May be reported to the IPC with commentary, but without an accompanying classification as P or R. R=susceptible, R=resistant Microbiological susceptibility Prevalence of acquired resistance may vary geographically and over time for selected species, so local information regarding resistance is desirable, especially when treating severe infections . If necessary, expert advice should be sought if the local prevalence of resistance is such that the use of the drug in at least some types of infections is controversial. Cefuroxime is generally active against the following microorganisms in vitro. Sensitive microorganisms Gram-positive aerobes: Staphylococcus aureus (methicillin-sensitive)* Coagulase negative staphylococcus (methicillin-sensitive) Streptococcus pyogenes Streptococcus agalactiae Gram-negative aerobes: Haemophilus influenzae Haemophilus parainfluenzae Moraxella catarrhalis Spirochetes: Borrelia burgdorferi Micro organisms for which acquired resistance is possible Gram-positive aerobes: Streptococcus pneumoniae Gram-negative aerobes: Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Proteus mirabilis Proteus spp. (other than P. vulgaris) Providencia spp. Gram-positive anaerobes: Peptostreptococcus spp. Propionibacterium spp. Gram-negative anaerobes: Fusobacterehum spp. Bacteroides spp. Naturally resistant microorganisms Gram-positive aerobes: Enterococcus faecaiis Enterococcus faecium Gram-negative aerobes: Acinetobacter spp. Campylobacter spp. Morganella morganii Proteus vulgaris Pseudomonas aeruginosa Serratia marcescens Gram-negative anaerobes: Bacteroides fragilis Others: Chlamydia spp. Mycoplasma spp. Legionella spp. *All methicillin-resistant S. aureus are resistant to cefuroxime.
Pharmacokinetics
Pharmacokinetics Absorption: after oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and is rapidly hydrolyzed in the intestinal mucosa and blood, releasing cefuroxime into the bloodstream. Cefuroxime axetil is optimally absorbed when taken immediately after meals. Following administration of cefuroxime axetil tablets, peak serum concentrations (2.1 mcg/mL for the 125 mg dose, 4.1 mcg/mL for the 250 mg dose, 7.0 mcg/mL for the 500 mg dose, and 13.6 mcg/mL for the 1000 mg dose) are achieved after approximately 2 -3 hours after taking the dose with food. The extent of absorption of cefuroxime from suspension is reduced compared to tablets, resulting in later and lower peak serum levels and reduced systemic bioavailability (4-17% less). Cefuroxime axetil oral suspension was not bioequivalent to cefuroxime axetil tablets when tested in healthy volunteers and therefore they are not interchangeable on a milligram-for-milligram basis (see Dosage and Administration section). The pharmacokinetics of cefuroxime are linear over the oral dose range from 125 to 1000 mg. Cefuroxime does not accumulate after repeated oral doses of 250 to 500 mg. Distribution: Protein binding ranges from 33 to 50%, depending on the methodology used. After a single dose of cefuroxime axetil, 500 mg tablets, was administered to 12 healthy volunteers, the volume of distribution was 50 L (CV%=28%). Concentrations of cefuroxime exceeding the minimum inhibitory concentrations for common pathogens can be achieved in the tonsils, sinus tissue, bronchial mucosa, bone, pleural fluid, intraarticular fluid, synovial fluid, interstitial fluid, bile, sputum and aqueous humor. Cefuroxime penetrates the blood-brain barrier during inflammation of the meninges. Biotransformation: cefuroxime is not metabolized. Elimination: The serum half-life is 1 to 1.5 hours. Cefuroxime is eliminated by glomerular filtration and tubular secretion. Renal clearance ranges from 125 to 148 ml/min/1.73 m2. Special groups of patients Gender: There were no differences in the pharmacokinetics of cefuroxime between men and women. Elderly Patients: No special precautions are required in elderly patients with normal renal function when using doses up to the usual limit of 1 g per day. Elderly patients are more likely to have decreased renal function, so the dose should be adjusted according to the renal function of elderly patients (see section "Dosage and Administration"). Children: In infants over 3 months of age and in children, the pharmacokinetics of cefuroxime are similar to those in adults. There are no clinical trial data on the use of cefuroxime axetil in children under 3 months of age. Renal impairment: The safety and effectiveness of cefuroxime axetil in patients with renal impairment have not been established. Cefuroxime is excreted primarily by the kidneys. Accordingly, as with the use of all similar antibiotics, in patients with significant impairment of renal function (i.e. creatinine clearance MIC).
Indications for use
Zinnat is indicated for the treatment of the following infectious diseases in adults and children over 3 months of age (see sections “Precautions” and “Pharmacodynamics”): - Acute streptococcal tonsillitis and pharyngitis; — Acute bacterial sinusitis; — Acute otitis media; — Exacerbation of chronic bronchitis; - Cystitis; - Pyelonephritis; — Uncomplicated infections of the skin and soft tissues; — Treatment of Lyme disease at an early stage. Official guidelines on the rational use of antibacterial agents should be considered.
Directions for use and doses
Dosage regimen The standard course of therapy is seven days (from five to ten days). Table 1. Adults and children (≥40 kg) Indication - Dosage regimen Acute tonsillitis and pharyngitis, acute bacterial sinusitis 250 mg twice daily Acute otitis media 500 mg twice daily Exacerbation of chronic bronchitis 500 mg twice daily Cystitis 250 mg twice daily Pyelonephritis 250 mg twice daily Uncomplicated skin and soft tissue infections 250 mg twice daily Lyme disease 500 mg twice daily for 14 days (10 to 21 days) Table 2. Children (
Use during pregnancy and lactation
Pregnancy Data on the use of cefuroxime in pregnant women are limited. Animal studies have shown no harmful effects on pregnancy, embryonic or fetal development, childbirth or postnatal development. Zinnat should be prescribed to pregnant women only if the benefits outweigh the risks. Breastfeeding Cefuroxime is excreted into breast milk in small quantities. Adverse events are not expected when using therapeutic doses, although the risk of diarrhea and fungal infection of the mucous membranes cannot be excluded. Due to these effects, discontinuation of breastfeeding may be necessary. The possibility of sensitization should be considered. During breastfeeding, cefuroxime should be used only after an assessment of the benefits and risks by your healthcare professional. Fertility There are no data on the effects of cefuroxime axetil on fertility in humans. Reproductive studies in animals have demonstrated no effect on fertility.
Precautionary measures
Hypersensitivity reactions Particular caution should be exercised when prescribing the drug to patients with a history of an allergic reaction to penicillins or other beta-lactam antibiotics due to the risk of cross-sensitivity. As with other beta-lactam antibiotics, serious and sometimes fatal hypersensitivity reactions have been reported. In case of severe hypersensitivity reactions, treatment with cefuroxime should be stopped immediately and adequate emergency treatment should be provided. Before starting therapy, it should be established whether the patient has a history of severe hypersensitivity reactions when using cefuroxime, other cephalosporins or other beta-lactam antibiotics. Caution should be exercised when prescribing cefuroxime to patients with a history of mild hypersensitivity to other beta-lactam antibiotics. Jarisch-Herxheimer reaction Some patients may experience increased temperature (fever), chills, headache, muscle pain, and skin rash while taking Zinnat to treat Lyme disease. This reaction is known as the Jarisch-Herxheimer reaction. It is directly due to the bactericidal activity of cefuroxime axetil against the causative agent of Lyme disease, the spirochete Borrelia burgdorferi. Symptoms usually last from several hours to one day. Patients should be informed that these symptoms are a typical consequence of the use of antibiotics for this disease and, as a rule, resolve without treatment (see section "Side effects"). Overgrowth of non-susceptible microorganisms As with other antibiotics, the use of cefuroxime axetil may lead to overgrowth of Candida fungi. Long-term use may also lead to overgrowth of other non-susceptible organisms (eg, enterococci and Clostridium difficile), which may require discontinuation of treatment (see Side Effects section). Pseudomembranous colitis, which can range in severity from mild to life-threatening, has been reported with the use of virtually all antibacterial agents, including cefuroxime. This diagnosis should be considered in patients with diarrhea occurring during or after use of cefuroxime (see section "Side effects"). Consideration should be given to discontinuing treatment with cefuroxime and initiating treatment against Clostridium difficile. You should not prescribe medications that inhibit peristalsis (see section “Side effects”). Impact on diagnostic tests A positive Coombs test associated with the use of cefuroxime may interfere with the cross-matching test (see section "Side effects"). When performing a ferrocyanide test, a false negative result may be observed, therefore, it is recommended to use glucose oxidase or hexokinase methods to determine the level of glucose in the blood or plasma of patients taking cefuroxime axetil. Important information about excipients The sucrose content of cefuroxime axetil suspension should be taken into account when treating patients with diabetes and appropriate recommendations should be given. Contains 3 g of sucrose per 5 ml dose. Contains 6 mg of propylene glycol (E1520) per 5 ml dose, which is equivalent to 60 mg in 50 ml of the finished suspension (contained in the “Tutti-frutti” flavor). The drug should not be used in patients with congenital fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency. With long-term use (two weeks or more), sucrose can cause damage to teeth. Cefuroxime axetil suspension contains 21 mg of aspartame per 5 ml dose, which is equivalent to 210 mg in 50 ml of the finished suspension. Aspartame is a source of phenylalanine and may be harmful to the health of patients with phenylketonuria, a rare inherited disease in which phenylalanine accumulates due to impaired excretion of phenylalanine from the body. Therefore, this drug should be prescribed with caution to patients with phenylketonuria. There are no clinical or preclinical data available to evaluate the use of aspartame in infants less than 12 weeks of age.
Interaction with other drugs
Drugs that reduce gastric acidity may reduce the bioavailability of cefuroxime when compared with that observed after taking the drug on an empty stomach, and also reduce the effect of increased absorption of the drug after meals. Cefuroxime axetil can affect the intestinal microflora, which leads to a decrease in the reabsorption of estrogens and, as a result, a decrease in the effectiveness of oral hormonal combined contraceptives. If oral contraceptives are used during treatment with Zinnat, patients should also use barrier methods of contraception (for example, a condom) and consult a doctor for appropriate recommendations. Cefuroxime is eliminated by glomerular filtration and tubular secretion. Concomitant use of probenecid is not recommended. Concomitant use of probenecid significantly increases the peak concentration, area under the serum concentration curve, and half-life of cefuroxime. Concomitant use with oral anticoagulants may lead to an increase in INR.
Contraindications
Hypersensitivity to cefuroxime or any excipient. Hypersensitivity to cephalosporin antibiotics. History of severe hypersensitivity reaction (eg, anaphylactic reaction) to any other type of beta-lactam antibacterial agent (eg, penicillins, monobactams, or carbapenems).
Compound
Component - Amount in % (wt/wt) - Amount per dose (g/5 ml) Active ingredient: Cefuroxime axetil1 - 3.553 - 0.1502 Excipients: Stearic acid1 - 20.19 - 0.852 Sucrose - 72.56 - 3.062 Tutti-frutti flavoring - 2.37 - 0.100 Acesulfame potassium - 0.50 - 0.021 Aspartame - 0.50 - 0.021 Povidone-K30 - 0.31 - 0.013 Xanthan gum - 0.02 - 0.001 1. Cefuroxime axetil and stearic acid are present in the form of a complex stearic acid - cefuroxime axetil 15% (SACA), the amount of which depends on the quantitative content of cefuroxime axetil in the original substance. 2. Equivalent to 125 mg of cefuroxime. 3. Equivalent to 2.96% (w/w) cefuroxime.
Overdose
Overdose may result in neurological effects including encephalopathy, seizures and coma. Symptoms of overdose may occur if the dose is not appropriately reduced in patients with renal impairment (see Dosage and Administration and Precautions). Serum concentrations of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.
Side effect
The most common adverse reactions are Candida overgrowth, eosinophilia, headache, dizziness, gastrointestinal disturbances, and transient increases in liver enzyme levels. The frequency categories assigned to the adverse reactions listed below are approximate because for most reactions, appropriate data (eg, from placebo-controlled studies) for frequency calculations are not available. In addition, the incidence of adverse reactions associated with cefuroxime axetil may vary depending on the indication for use. Data from large clinical trials were used to determine the frequency of adverse effects from very common to rare. The frequency assigned to all other unwanted effects (for example, those occurring with frequency
Storage conditions
At a temperature not exceeding 30 °C. Store the prepared suspension in the refrigerator at a temperature of 2-8 °C for no more than 10 days. Keep out of the reach of children.
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