Zinnat - instructions for use, dose, side effects, contraindications

Name of components	Amount, mg
	Dosage of 125 mg		Dosage of 250 mg
Active substance
Cefuroxime axetil¹	150,36		300,72
(in terms of cefuroxime)	125		250
Excipients
Microcrystalline cellulose²	47,51		95,03
Croscarmellose sodium	20,00		40,00
Sodium lauryl sulfate	2,25		4,50
Vegetable oil, hydrogenated	4,25		8,50
Silica colloidal dioxide	0,63		1,25
Tablet core weight	225,00		450,00
Film sheath
Hypromellose	5,55		7,40
Propylene glycol	0,33		0,44
Methylparahydroxybenzoate	0,06		0,07
Propyl parahydroxybenzoate	0,04		0,06
Dye Oprasprey	1,52		2,03
Nominal Film Sheath Weight		7,5	10,0
Weight of a tablet		232,5	460

Dyestuff composition

Colour	Name of components	Amount, %
White	Hypromellose	3,0
	Titanium dioxide	36,0
	Sodium benzoate	0,1

Notes:

¹- the amount of cefuroxime axetil is adjusted depending on the purity of the substance series used.

²- the amount of microcrystalline cellulose is adjusted to maintain the constant mass of the core.

Description:

Tablets coated with a film coating, 125 mg: tablets of the oval form, biconcave, film-coated, white or almost white, on one side of which engraved "GXES5 ".The cross section of the nucleus is white or almost white.

Film-coated tablets, 250 mg: tablets of the oval form, biconcave, film-coated, white or almost white, on one side of which engraved "G ES7 ".The cross section of the nucleus is white or almost white.

Pharmacotherapeutic group:Antibiotic-cephalosporin

ATX: & nbsp

J.01.D.C.02 Cefuroxime

Pharmacodynamics:

Mechanism of action

Cefuroxime axetil is a prodrug of cefuroxime, an antibiotic of the second generation cephalosporins with bactericidal action. Cefuroxime is active against a wide range of pathogens, including strains producing beta-lactamases.

Cefuroxime has resistance to the action of bacterial beta-lactamases, therefore it is effective against ampicillin-resistant and amoxicillin-resistant strains.

The bactericidal effect of cefuroxime is associated with the suppression of bacterial cell wall synthesis as a result of binding to the main target proteins.

Pharmacodynamic effects

The prevalence of acquired bacterial resistance to cefuroxime varies depending on the region and over time, in certain types of microorganisms, resistance can be very high. It is preferable to have local sensitivity data, especially when treating severe infections.

Cefuroxime is usually active in vitro against the following microorganisms.

Bacteria, usually sensitive to cefuroxime

Gram-positive aerobes

Staphylococcus aureus (strains sensitive to methicillin)¹

Coagulase-negative staphylococci (strains sensitive to methicillin)

Streptococcus pyogenes1

Beta-hemolytic streptococci

Gram-negative aerobes

Naeophilus influenzae¹, including ampicillin-resistant strains

Naeophilus parainfluenzae¹

Moraxella catarrhalis¹

Neisseria gonorrhoeae¹, including strains that produce and do not produce penicillinase

Gram-positive anaerobes

Pertostreptococcus spp.

Рropionibacterium spp.

Spirochetes

Vorelia burgdorferi¹

Bacteria for which the acquired resistance to cefuroxime is likely

Gram-positive aerobes

Streptococcus pneumoniae¹

Gram-negative aerobes

Citobacter spp., with the exception of C. freundii

Enterobacter spp, with the exception of E. aerogenes and E. colacae

Escherichia coli¹

Clebsily spp., including Kiebsiella pneuomonidae¹

Рroteus mirabilis

Рroteus srp., with the exception of P. renieri and P. vulgaris

Rovidencia srr.

Gram-positive anaerobes

Сlostridium srp.. with the exception of C. difficile

Gram-negative anaerobes

Vateroides spp., With the exception of V. fragilis

Fusobacterium spp.

Bacteria that have natural resistance to cefuroxime

Gram-positive aerobes

Enterococcus spp., including E. faecalis and E. faecium

Listeria monocytogenes

Gram-negative aerobes

Acinetobacter spr.

Virkholderia cepacia

Saprubobacter spp.

Citrobacter freundii

Epterobacter aerogenes

Enterobacter cloacae

Morganella morganii

Рroteus penneri

Рroteus vulgaris

Pseudomonas spp. Including Pseudomonas aeruginosa

Serratia spp.

Stenotrophomonas maltophilia

Gram-positive anaerobes

Сlostridium difficile

Gram-negative anaerobes

Vateroides fragilis

Other

Chlamydia spp.

Musorhassa spp.

Legionella spp.

¹ - for these bacteria, the clinical efficacy of cefuroxime has been demonstrated in clinical studies.

Pharmacokinetics:

Suction

After oral administration of cefuroxime, the auxetil is absorbed from the gastrointestinal tract and quickly hydrolyzed in the mucosa of the small intestine and in the blood with the release of cefuroxime. Optimum absorption of cefuroxime axetil in the form of tablets coated with a film coat is achieved on condition that the drug is taken immediately after a meal. Maximum whey concentrations of cefuroxime (2.1 mg / L for a dosage of 125 mg, 4.1 mg / L for a dosage of 250 mg, 7.0 mg / L for a dosage of 500 mg) are observed after approximately 2-3 hours when taking the drug while eating.

Distribution

The connection with plasma proteins is approximately 33-50% and depends on the technique of determination.

Metabolism

Cefuroxime is not metabolized.

Excretion

The half-life is 1-1.5 hours. Cefuroxime Excreted by glomerular filtration and tubular secretion. With simultaneous administration of probenecid, the area under the concentration-time curve increases by 50%.

Patients with impaired renal function

The pharmacokinetics of cefuroxime were studied in patients with renal dysfunction of varying severity. The half-life of cefuroxime increases as the function of the kidneys decreases, which is the basis for the recommendations for correcting the dosing regimen for this group of patients (see the "Application and dose" section). Patients on hemodialysis have at least 60% of the total amount of cefuroxime present in the body at the time of dialysis start, will be removed within a 4-hour dialysis period. Thus, an additional single dose of cefuroxime should be administered after completion of the hemodialysis procedure.

Indications:

The drug is indicated for the treatment of infections caused by susceptible to cefuroxime bacteria:

- upper respiratory tract infections, ENT organs such as otitis media, sinusitis, tonsillitis and pharyngitis;

- infections of the lower respiratory tract, for example, pneumonia, acute bacterial bronchitis and exacerbation of chronic bronchitis;

- urinary tract infections, for example, pyelonephritis, cystitis and urethritis;

- infections of the skin and soft tissues, for example, furunculosis, pyoderma and impetigo;

- gonorrhea: acute uncomplicated gonorrhea urethritis and cervicitis;

- treatment of borreliosis (Lyme disease) at an early stage and with the subsequent prevention of late stages of the disease in adults and children over 12 years of age.

Cefuroxime is also available as a sodium salt (Zinacef® preparation) for parenteral administration. This allows for stepwise therapy, using a transition from the parenteral form to the oral form of cefuroxime, if there is a clinical indication for this.

If necessary, stepwise therapy is indicated in the treatment of pneumonia and exacerbation of chronic bronchitis. The sensitivity of bacteria to cefuroxime varies depending on the region and over time. Wherever possible, local sensitivity data should be taken into accountsection "Pharmacological properties").

Contraindications:

- Hypersensitivity to beta-lactam antibiotics (in particular, to cephalosporin antibiotics, penicillins and carbapenems in history);

- Children under 3 years of age (for children from 3 months to 3 years, use Zinnat®, pellets for the preparation of a suspension for oral administration).

Carefully:Caution should be exercised when used in patients with impaired renal function; diseases of the gastrointestinal tract (including in the history, as well as ulcerative colitis); pregnant women, during breastfeeding.

Pregnancy and lactation:

Zinnat® should be used if the potential benefit to the mother exceeds the potential risk to the fetus and the baby.

Pregnancy

Experimental There is no evidence of embryopathic or teratogenic effects of cefuroxime axetil, but as with other medications, caution should be exercised when prescribing it in the early stages of pregnancy.

Breastfeeding period

Care should be taken when prescribing it to nursing mothers, since the drug is excreted in breast milk.

Dosing and Administration:

The standard course of therapy is 7 days (can vary from 5 to 10 days).

For optimal absorption, the drug should be taken after meals.

Adults

Most infections	250 mg twice daily
Urinary tract infections (cystitis, urethritis)	125 mg twice daily
Pyelonephritis	250 mg twice daily
Light and medium-heavy infection lower respiratory paths, for example, bronchitis	250 mg twice daily
Heavier infection lower respiratory ways or suspicion of pneumonia	500 mg twice a day
Uncomplicated gonorrhea	Single dose 1 g
Borreliosis (Lyme disease) in adults and children over 12 years of age	500 mg twice a day for 20 days

Stepwise therapy

Cefuroxime is also available as a sodium salt (preparation Zinacef®) for parenteral administration, which allows you to assign the same antibiotic consistently, when you need to switch from parenteral to oral therapy. Zinnat® is effective after the parenteral use of Zinacef® for the treatment of pneumonia and exacerbation of chronic bronchitis. The duration of parenteral and oral treatment is determined by the severity of the infection and the clinical picture.

Pneumonia

The drug Zinacef® (cefuroxime in the form of sodium salt) at a dose of 1.5 g 2-3 times per day (intravenously or intramuscularly) for 48-72 hours, then the preparation Zinnat ® (cefuroxime axetil) inside at a dose of 500 mg 2 times a day for 7- 10 days.

Exacerbation of chronic bronchitis

The drug Zinacef® (cefuroxime in the form of sodium salt) at a dose of 750 mg 2-3 times per day (intravenously or intramuscularly) for 48-72 hours, then the preparation Zinnat ® (cefuroxime axetil) orally at a dose of 500 mg twice a day for 5-10 days .

Children from 3 years old

Most infections

125 mg (1 tablet of 125 mg) twice a day The maximum daily dose is 250 mg

Otitis media or more serious infections

250 mg (1 tablet of 250 mg or 2 tablets of 125 mg) twice a day

The maximum daily dose is 500 mg

Tablets of Zinnat® can not be broken and crushed. Therefore, this dosage form is not used to treat patients with difficulty swallowing, including small children who can not swallow the whole pill. For children, a Zinnat® preparation in the form of granules for cooking suspensions for oral administration.

Patients with impaired renal function

Excretion cefuroxime occurs mainly kidneys. Recommended reduce the dose cefuroxime in patients with severe violation of kidney function for compensation delayed excretion (see table below).

Clearance creatinine	T_1/2(hours)	Recommended dose
> 30 ml / min	1,4- 2,4	No dose adjustment is required.
10- 29 ml / min	4,6	The standard single dose every 24 hours.
<10 ml / min	16,8	The standard single dose is every 48 hours.
During hemodialysis	2-4	At the end of each dialysis session, take one additional standard single dose.

Side effects:

Undesirable reactions when applied cefuroxime aksetila usually expressed slightly, short-term and reversible.

Unwanted reactions presented below, are listed in accordance with the defeat of organs and organ systems and frequency occurrence. The frequency of occurrence is defined as follows: very often (≥ 1/10), often (≥ 1/100 and < 1/10), infrequently (≥ 1/1000 and <1/100), rarely (≥ 1/10 000 and <1/1 000), very rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.

Frequency of occurrence of undesirable reactions

Infectious and parasitic diseases

Often: excessive growth of the fungi of the genus Sandida.

Violations of the blood and lymphatic system

Often: eosinophilia.

Infrequent: Coombs positive test, thrombocytopenia, leukopenia (sometimes severe).

Very rarely: hemolytic anemia.

Cephalosporins are absorbed on the surface of the cell membrane of erythrocytes, binding to antibodies to cephalosporins, which leads to a positive result of the Coombs reaction (which may affect cross-compatibility) and, in very rare cases, hemolytic anemia.

Immune system disorders

Hypersensitivity reactions, including:

Infrequent: skin rash.

Rarely: hives, itching.

Very rarely: drug fever, serum sickness, anaphylaxis.

Disturbances from the nervous system

Often: headache, dizziness.

Disorders from the gastro- intestinal tract

Often: gastrointestinal disorders, including diarrhea, nausea, abdominal pain.

Infrequently: vomiting.

Rarely: pseudomembranous colitis (see section "Special instructions").

Disorders from the liver and bile ducts

Often: transient increase in the activity of "hepatic" enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase).

Rarely: jaundice (mostly cholestatic), hepatitis.

Disturbances from the skin and subcutaneous tissue

Rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (necrotic nephrolysis).

See also "Immune system disorders".

Overdose:

Symptoms

An overdose of cephalosporins can cause an increase in the excitability of the brain, leading to the development of seizures.

Symptomatic treatment

Serum concentrations of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.

Interaction:

Drugs that reduce the acidity of gastric juice can reduce the bioavailability of cefuroxime axetil when compared with the observed after taking the drug on an empty stomach, and also level the effect of increased absorption of the drug after ingestion. Like other antibiotics, Zinnat ® can affect the intestinal microflora, which leads to a decrease in the reabsorption of estrogens and, consequently, to a decrease in the effectiveness of oral combined contraceptives.

When carrying out a ferrocyanide test, a false negative result can be observed,therefore glucose oxidase or hexokinase methods are recommended to determine the level of glucose in the blood and / or plasma. The drug Zinnat ® does not affect the quantitative determination of creatinine by the alkaline-picrate method. Simultaneous treatment with the "loop" diuretics slows tubular secretion and reduces renal clearance, increases the concentration in plasma and increases the half-life of cefuroxime.

With simultaneous administration with aminoglycosides and diuretics, the risk of nephrotoxic effects increases.

Special instructions:Before use, you must carefully collect allergic history.

In the process of treatment, it is necessary to monitor kidney function, especially in patients receiving the drug in a high dose.

During the period of taking Zinnat®, a false positive urine reaction to glucose is possible.

As with other antibiotics, taking Zinnat® can lead to excessive growth of the fungi of the genus Sandida. Long-term use can cause the growth of insensitive microorganisms (for example, enterococci and Clostridium difficile), which may require discontinuation of treatment.There are cases of pseudomembranous colitis occurring when taking antibiotics, the severity of which can range from mild to life-threatening. Therefore, it is necessary to conduct differential diagnosis of pseudomembranous colitis in patients with diarrhea that occurred during or after a course of antibiotic treatment. If diarrhea is prolonged or severe, or the patient experiences abdominal cramps, treatment with Zinnat® should be stopped immediately and the patient should be examined.

The Yarisch-Gerxheimer reaction was observed in borreliosis (Lyme disease) with the administration of Zinnat® and is due to the bactericidal activity of the drug against the causative agent of spirochaete Vörrelia burgdorferi. Patients should be informed that these symptoms are a typical consequence of the use of antibiotics in this disease.

With stepwise therapy, the time for switching to oral therapy is determined by the severity of the infection, the clinical condition of the patients and the sensitivity of the pathogen. If the clinical effect is not achieved within 72 hours from the start of treatment, the parenteral course of therapy should be continued.Before the start of the stepwise therapy, carefully read the instruction for the use of the sodium salt of cefuroxime for parenteral administration (preparation Zinacef®).

Effect on the ability to drive transp. cf. and fur:Since cefuroxime axetil may cause dizziness, it is necessary to warn patients about precautions when driving a vehicle or working with moving machinery.

Form release / dosage:

Tablets, film-coated, 125 mg, 250 mg.

Packaging:For 10 tablets in A1 / PVC-A1 blister. For 1 blister, along with instructions for use in a cardboard bundle.

Storage conditions:At a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015531 / 01

Date of registration:06.03.2009 / 12.02.2014

Expiration Date:Unlimited

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GLAXO OPERATIONS UK, Limited United Kingdom

Information update date: & nbsp14.10.2017

Illustrated instructions

Instructions

Zinnat® (Zinnat®)