Orpin

General characteristics. Structure:

Active ingredient: 1 g of cefazolin (in the form of sodium salt).

Pharmacological properties:

Pharmacodynamics. Cefazolin is a tsefalosporinovy antibiotic of the I generation for parenteral use; possesses a wide range of antimicrobic action; works bakteritsidno, breaking synthesis of components of a cell wall of microorganisms by blocking of the enzymes which are taking part in synthesis of a mukopeptid which is a part of a cellular membrane.

In vitro cefazolin is active concerning gram-positive microorganisms: Staphylococcus aureus (which both are producing, and not producing a penicillinase), Staphylococcus epidermidis; majority of strains of Streptococcus spp., including Streptococcus pneumoniae and beta and hemolitic streptococci of group A; gram-negative microorganisms: Salmonella spp., Escherichia coli, Shigella spp., Proteus mirabilis, Klebsiella spp., Haemophilus influenzae, Neisseria gonorrhoeae, Enterobacter aerogenes, Treponema spp.

Cefazolin is inefficient concerning Pseudomonas aeruginosa, indolpositive strains of Proteus spp. (including Proteus vulgaris), Providencia rettgeri, Enterobacter cloacae, Morganella morganii, Serratia spp., Staphylococcus spp strains., steady against Methicillinum, many strains of Enterococcus spp.

Pharmacokinetics. The maximum concentration (Cmax) after intramuscular introduction of 1 g of cefazolin is observed in 1 h and makes about 64 mkg/ml; Cmax after intravenous administration is observed in 5 min. and makes about 188 mkg/ml.

Cefazolin quickly gets into the majority of fabrics and liquids of an organism (bones, joints, tissues of heart and vessels, into an abdominal cavity, kidneys and urinary tract, a middle ear, airways, skin and soft tissues, and also into synovial, peritoneal and pericardiac liquids, a pleural exudate, into bile, a phlegm and urine), reaching in them therapeutic concentration; passes through a placenta and in small amounts it is allocated with breast milk.

Distribution volume - 0,12 l/kg. Communication with proteins of plasma - 85%.

Cefazolin is not metabolized. It is removed preferential by kidneys in not changed look (during the first 24 h - about 80%), and also with bile.

Elimination half-life at normal function of kidneys - about 1,8-2,0 h.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to cefazolin:
- upper and lower respiratory tracts;
- LOR-bodies, including average otitis;
- urinary tract and bodies of small gas;
- biliary tract;
- skin and soft tissues, including wound and burn fevers;
- bones and joints, including osteomyelitis;
- sepsis;
- peritonitis;
- mastitis;
- syphilis, gonorrhea;
- endocarditis.
Prevention of surgical infections in before - and the postoperative period.

Route of administration and doses:

Enter intramusculary or intravenously (struyno or kapelno).

Adults. The recommended doses for adults depending on the nature of an infection are specified in table 1.

Table 1.

 

Nature of an infection	Single dose	Introduction frequency
Moderately severe infections and heavy	0,5-1 g	Each 6-8 h
Easy form of the infection caused by sensitive gram-positive cocci	0,25-0,5 g	Each 8 h
Acute uncomplicated infection of urinary tract	1 g	Each 12 h
Pneumococcal pneumonia	0,5 g	Each 12 h
Heavy, zhizneugrozhayushchy infections, (for example, sepsis, endocarditis)	1-1,5 g	Each 6 h

The maximum daily dose - 6 g. The average duration of treatment - 7-10 days.

Prevention of surgical infections. Enter 1 g for 0,5-1 h before operation. At long operations - 0,5-1 g during operation. If necessary each 6-8 h within the first days after operation enter 0,5-1 g.

Adults with a renal failure. Change of the mode of dosing according to value of clearance of creatinine (table 2) after an initial dose which has to correspond to character and weight of an infection is required (see table 1).

Table 2.

Clearance of creatinine, ml/min.	Concentration of creatinine in plasma, % mg	% of a daily dose	Interval between introductions, hour
55 and more	1,5 and less	100	6-8
35-54	1,6-3,0	100	8
11-34	3,1-4,5	50	12
10 and less	4,6 and more	50	18-24

Children. An average daily dose for children (is more senior than month) - 25-50 mg/kg; at the heavy course of an infection the dose can be increased to 100 mg/kg/days. Frequency rate of introduction - 3-4 times a day.

Children with dysfunction of nights. Correction of the mode of dosing will see off depending on values of clearance kreati-Nin (table 3). All recommended doses enter after an initial dose which has to correspond to character and weight of an infection (see table 1).

Table 3.

Clearance of creatinine, ml/min.	% of a daily dose	Interval between introductions, hour
70-40	60	12
39-20	25	12
19-5	10	24

Preparation of solution and way of introduction. Intramusculary. 1 g of drug dissolve in 2,5 ml of water for injections or 0,9% of solution of sodium of chloride and enter deeply into a muscle (for example, into an upper outside quadrant of a gluteus). The approximate final volume and approximate final concentration of the received solution are specified in table 4.

Table 4.

Dosage	Solvent volume	Approximate final volume	Approximate final concentration
1 g	2,5 ml	3,0 ml	330 mg/ml

Intravenously. Struyno: 1 g dissolve in 10 ml of water for injections or 0,9% of solution of sodium of chloride; enter slowly within 3-5 min.

Kapelno: 1 g dissolve 5% of solution of glucose (dextrose) or 0,9% of a rastyovor of sodium of chloride in 100-250 ml; enter within 20-30 min. with a speed of 60-80 thaws into min.

During cultivation the bottle needs to be stirred up vigorously to a full rastvoyoreniye of powder.

Solution discoloration to yellowish does not mean loss of activity of drug. 

Features of use:

At emergence in the patient during treatment of diarrhea it is impossible to exclude the diagnosis of pseudomembranous colitis; in case of confirmation of such diagnosis treatment is stopped and appoint therapy according to severity of a complication.

At patients with a renal failure or a liver, at patients with disturbance of food, at patients, it is long accepting antibiotics, and at the patients who underwent treatment by anticoagulants it is necessary to control a prothrombin time. Administration of vitamin K can be required by such patients.

Purpose of drug in the absence of a bacterial infection or with the unjustified preventive purpose increases risk of development of resistant microorganisms.

Safety of use of cefazolin for premature children and children of the first year of life is not established.

Side effects:

Allergic reactions: skin rash, an itch, fever, an eosinophilia, a hyperthermia, a small tortoiseshell, it is rare - an acute anaphylaxis, a Quincke's edema, a bronchospasm, a multiformny exudative erythema (including Stephens-Johnson's syndrome).

From a nervous system: spasms.

From an urinary system: a renal failure at patients with diseases of kidneys at treatment by high doses (6 g/days); renal failure.

From the alimentary system: nausea, vomiting, diarrhea, an abdominal pain, anorexia, bleeding, a glossitis, oral candidiasis, it is rare - pseudomembranous colitis, hepatitis, cholestatic jaundice.

From bodies of a hemopoiesis: leukopenia, neutropenia, trombotsitopeiiya, thrombocytosis, hemolitic anemia.

Local reactions: seldom - morbidity in an injection site at an intramuscular vveyodeniye; at intravenous administration - phlebitis.

Laboratory indicators: tranzitorny increase in activity of "hepatic" transaminases and an alkaline phosphatase, a giperkreatininemiya, increase in a prothrombin time, false positive reaction to glucose in urine when using solution of Benedict or solution of Felinga, positive direct and indirect tests of Koombs.

Others: at prolonged treatment - dysbacteriosis, superinfection; genital candidiasis, colpitis.

Interaction with other medicines:

The concomitant use with anticoagulants and diuretics is not recommended. At simultaneous use of cefazolin and "loopback diuretics" there is a blockade of its canalicular secretion that leads to increase in concentration of cefazolin in blood.

The drugs blocking canalicular secretion increase concentration of cefazolin in blood, slow down its removal and increase risk of development of toxic reactions.

Aminoglycosides increase risk of damage of kidneys. Cefazolin pharmaceutical is incompatible with aminoglycosides (a mutual inactivation).

At simultaneous use with ethanol disulfiramopodobny reactions can be observed (spastic abdominal pains, nausea, vomiting, a headache, sudden rush of blood to the person).

Not to apply together with the antibacterial drugs having the bacteriostatic mechanism of action (tetracycline, streptocides, erythromycin, chloramphenicol) as between them and cefazolin there is an antagonism.

Solution of cefazolin is not recommended to be mixed in one syringe with other antibiotics.

Contraindications:

Hypersensitivity to antibiotics of a tsefalosporinovy row and another beta лактамным to antibiotics; pregnancy; children up to 1 month.

With care. At a renal failure and at intestines diseases, including colitis in the anamnesis; in the period of a lactation; at children till 1 year.

Overdose:

Symptoms: pain, inflammatory reactions and phlebitis in an injection site; dizziness, a headache, paresthesias, is possible development of spasms (especially at patients with renal failures).

Laboratory indicators: the increased level of creatinine, an urea nitrogen of blood, enzymes of a liver and bilirubin; positive reaction of Koombs; thrombocytosis and thrombocytopenia, eosinophilia, leukopenia, and also increase in a prothrombin time.

Treatment: to immediately stop administration of drug, to carefully control vital signs of an organism and the corresponding laboratory indicators; therapy - symptomatic. In hard cases carrying out a hemodialysis is possible. Peritoneal dialysis is not effective.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the term specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 1 g of cefazolin in the bottle from colourless glass corked by a rubber bung and which is rolled up by an aluminum cap with a plastic lid. On 1 bottle together with the application instruction or 50 bottles with 3-5 application instructions in a cardboard pack.