I N S T R U C T S I I
for medical use of the medicinal product
Zinnat™
(Zinnat™)
Storage:
active substance: cefuroxime;
1 tablet contains cefuroxime (in the form of cefuroxime axetil) 125 mg or 250 mg or 500 mg;
auxiliary substances: microcrystalline cellulose, croscarmellose sodium (type A), sodium lauryl sulfate, hydrogenated vegetable oil, colloidal anhydrous silicon dioxide, hypromellose, propylene glycol, methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), Opaspray White M-1-7120J (contains sodium benzoate (E 211)).
Medicinal form. Coated tablets.
The main physicochemical properties: tablets, covered with a shell, biconvex in the form of a capsule, white or almost white in color; marked "GX ES5" on one side for tablets of 125 mg;
Tablets covered with a shell, biconvex in the form of a capsule, white or almost white in color; marked "GX ES7" on one side for tablets of 250 mg;
Tablets covered with a shell, biconvex in the form of a capsule, white or almost white in color; marked "GX EG2" on one side for 500 mg tablets.
Pharmacotherapeutic group. Antimicrobial agents for systemic use. Beta-lactam antibiotics. ATX code J01D C02.
Pharmacological properties.
Pharmacodynamics.
Cefuroxime axetil is an oral form of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to the action of most beta-lactamases and exhibits activity against a wide range of gram-positive and gram-negative microorganisms.
The bactericidal effect of cefuroxime is the result of inhibiting the synthesis of the cell membrane of microorganisms.
Acquired resistance to an antibiotic varies between regions and can change over time, and can vary significantly for individual strains. Local antibiotic susceptibility data should be consulted, if available, especially when treating severe infections.
Cefuroxime usually has activity against the following microorganisms in vitro:
Sensitive microorganisms:
Gram-positive aerobes:
Staphylococcus aureus (methicillin-susceptible)*
Coagulase-negative staphylococcus (methicillin-susceptible)
Streptococcus pyogenes
Streptococcus agalactiae
Gram-negative aerobes:
Haemophilus influenzae
Haemophilus parainfluenzae
Moraxella catarrhalis
Spirochetes:
Borrelia burgdorferi
Microorganisms whose acquired resistance may pose a problem:
Gram-positive aerobes:
Streptococcus pneumoniae
Gram-negative aerobes:
Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Proteus strains (other than P. vulgaris)
Providencia strains
Gram-positive anaerobes:
Peptostreptococcus strains
Propionibacterium strains
Gram-negative anaerobes:
Fusobacterium strains
Bacteroides strains
Resistant microorganisms:
Gram-positive aerobes:
Enterococcus faecalis
Enterococcus faecium
Gram-negative aerobes:
Acinetobacter strains.
Campylobacter strains
Morganella morganii
Proteus vulgaris
Pseudomonas aeruginosa
Serratia marcescens
Gram-negative anaerobes:
Bacteroides fragilis
Others:
Chlamydia strains
Mycoplasma strains
Legionella strains
*All methicillin-resistant S. aureus are nonsusceptible to cefuroxime.
Pharmacokinetics.
After oral administration of cefuroxime, axetil is absorbed in the intestine, hydrolyzed on the mucous membrane of the latter, and enters the bloodstream in the form of cefuroxime.
The optimal level of absorption is observed immediately after eating. The maximum level of cefuroxime in blood serum is observed approximately 2-3 hours after taking the drug. The half-life of the drug is approximately 1-1.5 hours. The level of protein binding is 33-55% depending on the method of determination. Cefuroxime is excreted unchanged by the kidneys by tubular secretion and glomerular filtration.
Simultaneous use of probenecid increases the area under the curve of the average serum concentration by 50%.
The level of cefuroxime in blood serum decreases due to dialysis.
Clinical characteristics.
Indication.
Zinnat is indicated for the treatment of infections listed below in adults and children aged 3 months and older.
– Acute streptococcal tonsillitis and pharyngitis.
– Acute bacterial sinusitis.
– Acute otitis media.
– Exacerbation of chronic bronchitis caused by pathogens sensitive to cefuroxime axetil.
- Cystitis.
– Pyelonephritis.
– Uncomplicated skin and soft tissue infections.
– Early manifestations of Lyme disease.
Contraindication.
Hypersensitivity to cephalosporin antibiotics, cefuroxime and any of the components of the drug. History of severe hypersensitivity reactions (for example, anaphylactic reactions) to any other type of beta-lactam antibiotics (penicillins, monobactams and carbapenems).
Interaction with other medicinal products and other types of interactions.
Drugs that reduce the acidity of gastric juice can reduce the bioavailability of Zinnat and have the property of eliminating the effect of improved absorption after taking food
Like other antibiotics, Zinnat can have an effect on the intestinal flora, which will lead to a decrease in the reabsorption of estrogens and a decrease in the effectiveness of combined oral contraceptives.
Since the ferrocyanide test can be falsely negative, it is recommended to use glucose oxidase or hexokinase methods to determine blood and plasma glucose levels in patients treated with cefuroxime axetil. Cefuroxime does not affect the alkaline-picrate analysis of creatinine.
Simultaneous use with probenecid leads to a significant decrease in the maximum concentration, the area under the curve "concentration in serum - time" and the half-life of cefuroxime. Therefore, simultaneous use with probenecid is not recommended.
Simultaneous use with oral anticoagulants can lead to an increase in the INR (international normalized ratio).
The level of cefuroxime in blood serum is reduced by dialysis.
There have been reports of a positive Coombs test during treatment with cephalosporins. This phenomenon can affect cross blood compatibility testing.
Features of application.
Hypersensitivity reactions
Particular care should be taken in patients with a history of allergic reactions to penicillins or other beta-lactam antibiotics, as there is a risk of cross-sensitivity. As with all beta-lactam antimicrobial medicinal products, serious and isolated fatal cases of hypersensitivity reactions have been reported. In the event of severe hypersensitivity reactions, treatment with cefuroxime should be stopped immediately and the patient provided with appropriate emergency medical care.
Before starting therapy, it is necessary to determine whether the patient has a history of severe hypersensitivity reactions to cefuroxime, other cephalosporins, or beta-lactam drugs of other types. Cefuroxime should be used with caution in patients with a history of mild hypersensitivity reactions to other beta-lactam drugs.
The use of cefuroxime axetil (as well as other antibiotics) can lead to Candida overgrowth. Long-term treatment may also lead to overgrowth of other non-susceptible organisms (eg Enterococci, Clostridium difficile), which may in turn require discontinuation of treatment.
With the use of antibiotics, pseudomembranous colitis can be observed, which can manifest itself from a mild form to a life-threatening condition. Therefore, it is important to keep this in mind if patients develop severe diarrhea during or after antibacterial therapy. If prolonged or severe diarrhea occurs or the patient experiences sharp, cramp-like abdominal pain, treatment should be discontinued immediately and the patient should be carefully examined.
During the treatment of Lyme disease with Zinnat, a Yaris-Herxheimer reaction was observed, which occurs directly due to the bactericidal effect of Zinnat on the microorganism that causes Lyme disease, the spirochete Borrelia burgdorferi. Patients should be advised that this is a common side effect of antibiotic therapy for Lyme disease that resolves without treatment.
During sequential therapy, the time of transition from parenteral to oral therapy is determined by the severity of the infection, the patient's clinical condition, and the sensitivity of the pathogen. In the absence of clinical improvement within 72 hours, parenteral therapy should be continued. Before starting sequential therapy, you should familiarize yourself with the relevant Instructions for the medical use of cefuroxime sodium.
Zinnat tablets contain parabens, which can cause allergic reactions (possibly of the delayed type).
Use during pregnancy or breastfeeding.
Pregnancy
There are limited data on the use of cefuroxime in pregnant women. In animal studies, no adverse effects of cefuroxime axetil on pregnancy, embryo and fetal development, childbirth, and postnatal development of the child were found. Zinnat should be prescribed to pregnant women only in cases where the benefit of using the medicine outweighs the possible risks.
Breast-feeding
Cefuroxime passes into breast milk in small amounts. When using therapeutic doses of the drug, the development of adverse reactions is not expected, but the risk of diarrhea or fungal infection of the mucous membranes cannot be excluded. Therefore, breast-feeding may need to be discontinued due to these reactions. The possibility of a sensitizing effect of the medicinal product should also be taken into account. Cefuroxime is prescribed during breastfeeding only after the doctor has evaluated the ratio of benefits and risks of its use.
Fertility
There are no data on the effect of cefuroxime axetil on human fertility. In studies of reproductive function on animals, no effect of this medicinal product on fertility was recorded.
The ability to influence the speed of reaction when driving vehicles or other mechanisms.
Because the drug can cause memory loss ration, patients should be warned that driving a car and working with other mechanisms should be done with caution.
Method of application and dosage.
Antibiotic susceptibility varies by region and may change over time. If necessary, local antibiotic susceptibility data should be consulted.
Usually, the duration of treatment is 7 days (it can be from 5 to 10 days).
For better absorption, the drug is recommended to be taken after a meal.
The dosage of the drug for adults and children depending on the infection is shown in tables 1, 2.
Adults and children ( 40 kg) Table 1
Indications for use Dose
Acute tonsillitis and pharyngitis, acute bacterial sinusitis 250 mg 2 times a day
Acute otitis media 500 mg 2 times a day
Exacerbation of chronic bronchitis 500 mg 2 times a day
Cystitis 250 mg 2 times a day
Pyelonephritis 250 mg 2 times a day
Uncomplicated skin and soft tissue infections 250 mg 2 times a day
Lyme disease 500 mg 2 times a day for 14 days (therapy can last from 10 to 21 days)
Children (< 40 kg) Table 2
Indications for use Dose
Acute tonsillitis and pharyngitis, acute bacterial sinusitis 10 mg/kg 2 times a day, maximum dose – 125 mg 2 times a day
Children aged 2 years and older with otitis media or, if necessary, with more serious infections 15 mg/kg 2 times a day, the maximum dose is 250 mg 2 times a day
Cystitis 15 mg/kg 2 times a day, maximum dose – 250 mg 2 times a day
Pyelonephritis 15 mg/kg 2 times a day, maximum dose – 250 mg 2 times a day for 10-14 days
Uncomplicated skin and soft tissue infections 15 mg/kg 2 times a day, the maximum dose is 250 mg 2 times a day
Lyme disease 15 mg/kg 2 times a day, maximum dose – 250 mg 2 times a day for 14 days (from 10 to 21 days)
Zinnat tablets cannot be broken, so they are not prescribed to patients who cannot swallow them. Children are recommended to prescribe the drug in the form of a suspension.
Cefuroxime acetyl tablets and cefuroxime acetyl granules for suspension are not bioequivalent, so these dosage forms are not interchangeable when calculated in milligrams.
Cefuroxime is also available as a sodium salt for parenteral use. This makes it possible to carry out sequential therapy with one antibiotic when switching from parenteral administration to oral administration, if there are clinical indications for this.
Zinnat is effective for sequential treatment of exacerbations of chronic bronchitis after previous parenteral use of "Zinacef" (cefuroxime sodium).
Sequential therapy
Exacerbation of chronic bronchitis: 750 mg of cefuroxime 2-3 times a day (intravenously or intramuscularly) for 48-72 hours followed by Zinnat 500 mg 2 times a day orally for 5-10 days.
The duration of both parenteral and oral treatment should be determined taking into account the severity of the infection and the patient's condition.
Patients with renal failure
Cefuroxime is excreted mainly by the kidneys. In patients with severe renal impairment, it is recommended to reduce the dose of cefuroxime to compensate for its slower excretion (see table below).
Creatinine clearance T1/2 (hours) Recommended dosage
≥ 30 ml/min
1.4 – 2.4 Dose adjustment is not required (use a standard dose of 125 mg to 500 mg 2 times a day)
10 – 29 ml/min 4.6 Standard individual dose every 24 hours
<10 ml/min 16.8 Standard individual dose every 48 hours
During hemodialysis
2 – 4 One additional standard dose should be administered after each dialysis
Patients with liver failure
There are no data on the use of this medicine in patients with impaired liver function. Cefuroxime is excreted mainly by the kidneys, therefore, it is expected that the presence of impaired liver function will not affect the pharmacokinetics of cefuroxime.
Children.
There is no experience of using cefuroxime axetil for the treatment of children under 3 months of age.
Zinnat tablets cannot be broken, so they are not prescribed to patients who cannot swallow them. Children are recommended to prescribe the drug in the form of a suspension.
Overdose.
Cephalosporin overdose can cause brain irritation and neurological complications, including encephalopathy, convulsions, and coma. Overdose symptoms may occur if the dose of the drug has not been appropriately adjusted for patients with impaired renal function (see sections "How to use and dosage" and "Particulars of use").
Cefuroxime serum levels can be reduced by hemodialysis and peritoneal dialysis.
Adverse reactions.
Side effects when using cefuroxime axetil are expressed moderately and are mostly reversible.
Adverse reactions, information about which is given below, are classified by organs and systems and by the frequency of their occurrence. According to the frequency of occurrence, they are divided into the following categories:
very common ≥ 1 in 10, often ≥ 1 in 100 and < 1 in 10, uncommon ≥ 1 in 1,000 and < 1 in 100, rarely ≥ 1
in 10,000 and < 1 in 1,000, very rarely < 1 in 10,000.
Infections and infestations
Common: Candida overgrowth.
Not known: Clostridium difficile overgrowth.
From the blood and lymphatic system
Often: eosinophilia.
Infrequent: positive Coombs test, thrombocytopenia, leukopenia (sometimes profound).
Very rare: hemolytic anemia.
Cephalosporins as a class have the property of being absorbed on the surface of the erythrocyte membrane and interacting there with antibodies, which can lead to a positive Coombs test (affecting the determination of blood compatibility) and (very rarely) to hemolytic anemia.
From the side of the immune system
Hypersensitivity reactions, including
Infrequent: skin rashes.
Rarely: urticaria, itching.
Very rarely: medicinal fever, serum sickness, anaphylaxis.
Unknown: Yarysh-Herxheimer reaction.
From the side of the nervous system
Often: headache, dizziness.
From the side of the digestive tract
Common: Gastroenterological disorders, including diarrhea, nausea, abdominal pain.
Uncommon: vomiting.
Rarely: pseudomembranous colitis (see section "Particulars of use").
From the hepatobiliary system
Often: transient increase in the level of liver enzymes (ALT, AST, LDH).
Very rarely: jaundice (mainly cholestatic), hepatitis.
From the side of the skin and subcutaneous tissue
Very rarely: polymorphic erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (exanthematous necrolysis).
Not known: angioedema.
Children.
The safety profile of cefuroxime in children corresponds to a similar profile in adult patients.
Expiration date. 3 years.
Storage conditions.
Store at a temperature not higher than 30 C. Keep out of the reach of children.
Packaging. Blisters of 10 tablets in a cardboard package.
Leave category. By prescription.
Producer. Glaxo Operations UK Limited (Great Britain)/
Glaxo Operations UK Limited (United Kingdom).
The location of the manufacturer and the address of the place of its activity.
Glaxo Operations UK Limited, Harmere Road, Barnard Castle, Durham, DL12 8DT, United Kingdom/
