Cefazolin

General characteristics. Structure:

Active ingredient: 1 g of cefazolin of sodium salt.

Bactericidal antibiotic of a wide range of antibacterial action.

Pharmacological properties:

Pharmacodynamics. The Tsefalosporinovy antibiotic of the I generation for parenteral use. Works bakteritsidno, breaking synthesis of a cell wall of microorganisms. Has a broad spectrum of activity, it is active concerning gram-positive (Staphylococcus spp., Staphylococcus aureus (which are not producing and producing a penicillinase; including Streptococcus pneumoniae), Corynebacterium diphtheriae, Bacillus anthracis) and gram-negative (Neisseria menmghidis, Neisseria gonorrhoeae, Shigella spp., Salmonella spp., Escherichia coli, Klebsiella spp., Treponema spp., Leptospira spp.) microorganisms. It is active concerning Haemophilus influenzae, some strains of Enterobacter and Enterococcus. It is not effective concerning Pseudomonas aeruginosa, indolpositive strains of Proteus spp., Mycobacterium tuberculosis, Serratia spp., anaerobic microorganisms, metitsillinrezistentny strains of Staphylococcus spp

Pharmacokinetics. At oral administration cefazolin is not soaked up. The cefazolin entered intramusculary or intravenously creates high concentration in serum.

At intramuscular introduction (in oil) cefazolin is quickly soaked up from the place of an injection. After introduction of concentration in oil to blood higher and remain longer, than after introduction of the majority of other cephalosporins.

Peak concentration: after introduction of 0.5 g and 1 g to blood the following concentration are reached:

Dose in oil	Time after an injection (in hours) and concentration in blood (in mkg/ml)
	1/2	1.00	2.00	4.00	6.00	8.00	10:00
0.5	32.20	36.80	37.90	15:50	6.30	3.00	-
1,0 g	60.10	63.80	64.30	29.80	13:20	7.10	<4.1

Duration of plasma elimination half-life makes about two hours.

After 1 g, intravenous (in/in) introductions, the maximum concentration in serum in 188.4 mkg/ml is reached in 5 minutes, decreasing in 4 hours to 16.5 mkg/ml.

Thanks to high and long levels cefazolin it is possible to enter into blood in a dose 1 g with an interval of 12 hours, using the convenient scheme of double introduction in days.

About 70-90% of the entered dose contact proteins of plasma.

Cefazolin easily (gets into various fabrics and bodies, including and into almonds, a wall of a gall bladder and an appendix. Cefazolin is also found in high concentration in physiological liquids. For lack of obstruction of biliary tract in 4 hours after introduction of its concentration in bile surpass those in serum. Cefazolin reaches therapeutic concentration in ascitic and pleural liquid, inflammatory exudate, lungs, a liver, skin and soft tissues, joints, heart and a peritoneum, a middle ear. Very high concentration of cefazolin are created in kidneys - after introduction of 1 g of cefazolin its concentration in urine makes up to 4000 mkg/ml. Cefazolin passes through capillary membranes in bones and reaches bactericidal concentration in liquid of intersticial space of the healthy and affected with an osteomelitis bone.

In the absence of an infection of a meninx cefazolin is found in cerebrospinal fluid in extremely insignificant concentration therefore it is possible to consider that it does not pass through a blood-brain barrier.

Concentration of cefazolin in a blood-groove of a fruit is similar to that mother in a blood-groove. Cefazolin is found in milk of the feeding women in very low concentration.

Cefazolin is not metabolized in a liver and removed from an organism in not changed look.

Cefazolin is removed from an organism mainly with urine due to glomerular filtering and canalicular secretion. The amount of the cefazolin removed with urine makes during the first 6 h - 60–90%, in 24 h - 70–95% of the entered dose. Removal of cefazolin together with bile happens only in insignificant degree.

T1/2 from plasma increases at patients with renal failures to 20–40 h.

Indications to use:

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

Route of administration and doses:

Cefazolin is intended only for parenteral administration - intramusculary and intravenously (struyno or kapelno). Doses establish individually, taking into account weight of a current and localization of an infection, sensitivity of the activator.

Preparation of solutions and use. Intramusculary. Solution for injections in oil prepares by dissolution of dry matter in 0,5% solution of lidocaine or in 2-3 ml of water for injections.

For intravenous jet administration powder is dissolved in 10 ml of sterile water for injections (not less than 4 ml of solvent on 1 gram of dry matter).

In both cases after solvent addition the bottle needs to be stirred up intensively for full dissolution of powder.

Doses to 1 g of cefazolin can be entered in the form of slow intravenous injection (in 3-5 minutes). When using higher doses it is necessary to apply infusional introduction (during the period over 20 and up to 30 minutes).

For preparation of infusion solution it is possible to use 100-150 ml of 0,9% of solution of sodium of chloride of isotonic, 5% or 10% of solution of glucose or glucose with isotonic solution, and also glucose solution in Ringer's solution, 5% or 10% fructose solution on sterile water for injections, Ringer's solution for injections and isotonic solution, sodium bicarbonate. Drug is dissolved by 50-100 ml of 5-10% of solution of a dextrose, 0,9% of solution of sodium of chloride, Ringer's solution, 5% of solution of Natrii hydrocarbonas.

To use exclusively freshly cooked and transparent solutions. Possible yellowish coloring of solution after dissolution of powder is not the instruction on any change of properties of drug or on differences in its therapeutic effectiveness.

Instructions on a dosage for adults:

Type of an infection	Dose	Introduction frequency
Infections of an easy current, caused by sensitive gram-positive cocci	250-500 mg	Each 8 hours
Pneumococcal pneumonia	0.5	In 12 hours
Acute uncomplicated infections of urinary tract	1 g	In 12 hours
Moderately severe or heavy	0.5-1	In 6-8 hours
Heavy, life-threatening infections: endocarditis, septicaemia	1-1.5	In 6 hours

At purpose of cefazolin to adult patients with a renal failure:

Clearance of creatinine (ml/min.)	General daily dose ()	Dose/introduction ()	Interval between introductions (hour)
over 80	1-4	0,5-1,0	4-8
80-50	1-2	0,5-1,0	6-8
50-20	0,5-1,0	0,5	12-24
less than 20	0,5	0,25-0,5	12-24
hemodialysis	0,5 after each hemodialysis	0,5	80

Clearance of creatinine (ml/min.)	Initial dose	Maintenance dose	Approximate term between injections
50-80 ml/min.	0,5-1,0 g	It is equal to an initial dose	12 hour
30-50 ml/min.	0,5-1,0 g	It is equal to an initial dose	16-24 hour
25 ml/min.	0,5-1,0 g	1/2 initial doses	8 hour
20 ml/min.	0,5-1,0 g	1/2 initial doses	9-10 hour
15 ml/min.	0,5-1,0 g	1/2 initial doses	12 hour
10 ml/min.	0,5-1,0 g	1/2 initial doses	16 hour
5 ml/min.	0,5-1,0 g	1/2 initial doses	24 hour

Preoperative prevention. For prevention of infections during surgical interventions the dosage of cefazolin depends on type and duration of operation.

- 1 gram is entered intravenously or intramusculary in 30 min. - 1 hour prior to surgery (the dose is sufficient at insignificant surgical interventions of small duration);

- at long surgeries (more than 2 hours) in addition enter from 0,5 g to 1 g intravenously or intramusculary during the operation (depending on duration it is possible to enter also during surgery through certain periods);

- during the postoperative period after an initial dose enter doses from 0,5 g to 1 g intravenously or intramusculary with an interval of 6-8 hours within 24 hours;

- if the potential infection can pose a threat for the patient (for example, after heart operations or after extensive orthopedic operations, such as an arthroplasty), it is recommended to continue postoperative administration of cefazolin during the period from 3 to 5 days.

It is important to observe the terms stated above that during execution of a surgical section at serum and the patient's tissues there were already sufficient concentration of an antibiotic.

Use for children with normal function of kidneys. To children of 1 month is also more senior appoint - 25-50 mg/kg/days; frequency rate of introduction - 3-4 times a day. At the heavy course of an infection the dose can be increased to 100 mg/kg of body weight.

Use for patients with a renal failure. Patients with renal failures need change of the mode of dosing according to KK values: at KK of 55 ml/min. and more or at concentration of creatinine in plasma of 1.5 mg of % it is also less possible to enter a full dose; at KK of 54-35 ml/min. or concentration of creatinine in plasma of 3-1.6 mg of % it is possible to enter a full dose, but intervals between injections need to be increased to 8 h; at KK of 34-11 ml/min. or concentration of creatinine in plasma of 4.5-3.1 mg of % - ½ bucketed doses of 12 h; at KK of 10 ml/min. and less or at concentration of creatinine in plasma of 4.6 mg of % and more than-1/2 usual doses each 18-24 h. All recommended doses enter after the initial dose corresponding to the indication and weight of an infection.;

To children at whom the clearance of creatinine makes from 70 to 40 ml/min. / 1,73 m ² 60% of the average daily dose of cefazolin divided into two introductions are entered. To children at whom the clearance of creatinine makes from 40 to 20 ml/min. / 1,73 m ² 25% of the average daily dose of cefazolin divided into two introductions are entered. At clearance of creatinine between 20 and 5 ml/min. / 1,73 the m ² is appointed 10% of a standard daily dose of bucketed cefazolin at 24 o'clock. However in the beginning it is necessary to enter a usual load dose.

Features of use:

Use during pregnancy and during breastfeeding. Drug is contraindicated at pregnancy. It is necessary to stop breastfeeding in need of purpose of drug during this period.

The patients who had allergic reactions to penicillin, karbapenema in the anamnesis can have hypersensitivity to tsefalosporinovy antibiotics.

During treatment by cefazolin receiving positive direct and indirect tests of Koombs, and also false positive reaction of urine to sugar is possible.

At use of drug the exacerbation of diseases of digestive tract, especially colitis is possible. At emergence of the heavy diarrhea characteristic of pseudomembranous colitis, cefazolin it is necessary to cancel and appoint the corresponding treatment. During treatment patients should refrain from alcohol intake. At prolonged use of drug control of a picture of peripheral blood and function of kidneys is necessary.

Features of influence of medicine on ability to manage the vehicle and other mechanisms. It is necessary to be careful when driving and other potentially dangerous mechanisms.

Side effects:

Allergic reactions: hyperthermia, dermahemia, skin rash, small tortoiseshell, skin itch, toksikodermiya, bronchospasm, eosinophilia, Quincke's disease, arthralgia, acute anaphylaxis, multiformny exudative erythema (including Stephens-Johnson's syndrome).

From bodies of respiratory system: suffocation, short wind.

From a nervous system: dizziness, spasms.

From an urinary system: at patients with diseases of kidneys at treatment by high doses (6 g) - a renal failure (in these cases the dose is reduced and treatment is carried out under control of dynamics of concentration of an urea nitrogen and creatinine to blood).

From digestive tract: nausea, vomiting, diarrhea, abdominal pain, pseudomembranous colitis, cholestatic jaundice, hepatitis.

From system of a hemopoiesis: leukopenia, neutropenia, trombotsitemiya, thrombocytosis, hemolitic anemia. At prolonged treatment - dysbacteriosis, the superinfection caused by antibiotic-resistant strains, a candidiasis (including candidosis stomatitis). 

Laboratory indicators: false positive reaction of Koombs, increase in activity of "hepatic" transaminases, giperkreatininemiya, increase in a prothrombin time, false positive reaction of urine to glucose.

Local reactions: at introduction in oil – morbidity (in an injection site), at in introduction - phlebitis.

Interaction with other medicines:

It is not recommended to appoint cefazolin along with anticoagulants.

At simultaneous use to "loopback" diuretics (furosemide, Acidum etacrynicum) there is a blockade of canalicular secretion of cefazolin (it is necessary to avoid combined use).

The renal clearance of cefazolin decreases at a concomitant use of a probenetsid that results in the increased and more long concentration of cefazolin in blood.

Synergism of antibacterial action at a combination with aminoglikozidny antibiotics, Vancomycinum, rifampicin is noted. Aminoglycosides increase risk of development of damage of kidneys.

Pharmaceutical it is incompatible with aminoglycosides (a mutual inactivation).

Cefazolin, suppressing an indestinal flora, interferes with vitamin K synthesis. Therefore at simultaneous use with the drugs reducing aggregation of thrombocytes (nonsteroid protivospalitelny drugs (NPVP), salicylates) the risk of development of bleedings increases. For the same reason at simultaneous use with anticoagulants strengthening of anticoagulating action is noted. It is not necessary to apply cefazolin together with the antibakteralny drugs having the bacteriostatic mechanism of action (tetracyclines, streptocides, erythromycin, chloramphenicol) as the researches in vitro showed that between them there is an antagonism.

Cefazolin can cause Disulfiramum - similar reactions at simultaneous use with ethanol.

Contraindications:

Hypersensitivity to drugs of group of tsefalosporinovy and other β-laktamny antibiotics (including both penicillin and karbapenema), the neonatality period (up to 1 month). The concomitant use with anticoagulants and diuretics is not recommended.

With care. A renal failure, intestines diseases (including colitis in the anamnesis), children's age from 1 to 12 months.

Overdose:

Pain, inflammatory reactions in an injection site; dizziness, a headache, paresthesias, possible development of spasms (especially at patients with diseases of kidneys).

Laboratory indicators: the increased concentration of creatinine, an urea nitrogen of blood, enzymes of a liver and bilirubin; false 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 the vital functions of an organism and the corresponding laboratory indicators; therapy – symptomatic. In hard cases carrying out a hemodialysis is possible. Peritoneal dialysis is inefficient.

Storage conditions:

Period of validity 2 years. Not to apply the List B after a period of validity. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for intravenous and intramuscular administration of 1,0 g in bottles. On 50 bottles together with application instructions place a box from a cardboard (for hospitals).