Fortazim

General characteristics. Structure:

Active ingredient: 1 g of a ceftazidime in the form of a pentahydrate ceftazidime.

Excipients: sodium carbonate.

Pharmacological properties:

Pharmacodynamics. The Tsefalosporinovy antibiotic of the III generation for parenteral use. Works bakteritsidno. The mechanism of action is caused by oppression of synthesis of a cell wall of microorganisms. Высокоустойчив to action β-лактамаз, including penicillinases and цефалоспориназ. Has a broad spectrum of activity. The ceftazidime is active in the relation:

- gram-negative bacteria: Pseudomonas spp., including Pseudomonas aeruginosa, Pseudomonas pseudomallei, Klebsiella spp., including Klebsiella pneumoniae, Proteus mirabils, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia spp., Escherichia coli, Enterobacter spp., Citrobacter spp., Serratia spp., Salmonella spp., Shigella spp., Yersinia enterocolitica, Pasteurella multocida, Acinetobacter spp., Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, including ampitsillinrezistentny strains, Haemophilus parainfluenzae, including ampitsillinrezistentny strains,

- gram-positive bacteria: Staphylococcus aureus (strains sensitive to Methicillinum), Staphylococcus epidermidis (strains sensitive to Methicillinum), Micrococcus spp., Streptococcus pyogenes (a β-hemolitic streptococcus of group A), group Streptococcus In (Streptococcus agalactiae), Streptococcus pneumoniae, Streptococcus mitis, Streptococcus spp. (excepting Streptococcus faecalis),

- anaerobic bacteria: Peptococcus spp., Peptostreptococcus spp., Streptococcus spp., Propionibacterium spp., Clostridium perfingers, Fusobacterrium spp., Bacteroides spp. (the majority of strains of Bacteroides fragilis are resistant). In vitro the Ceftazidime is inactive concerning metitsil_nrezistentny stafilokokk, Streptococcus faecalis and many other enterococci, Listeria monocytogenes, Campylobacter spp., Clostrium difficile.

Pharmacokinetics. Therapeutic concentration of a ceftazidime in a blood plasma remain for 8-12 hours.

Distribution. Linkng with blood proteins makes 10%. Badly gets through the unimpaired blood-brain barrier. But at an inflammation of a meninx it is found in therapeutic concentration in cerebrospinal fluid.

Conclusion. The elimination half-life at patients with normal function of kidneys makes

1,8 hours, with an impaired renal function – 2,2 hours. The ceftazidime is removed in not changed look by glomerular filtering, 80-90% of a dose of drug are removed with urine within 24 hours.

Indications to use:

The infections caused by microorganisms, sensitive to drug:

• respiratory infections (including pneumonia at patients with a mucoviscidosis,
• infections at patients with reduced immunity,
• infections of skin and soft tissues,
• infections of ENT organs,
• infections of urinary tract,
• bacteremia, septicaemia,
• infections of bones and joints,
• infections of digestive tract, biliary tract and abdominal cavity,
• the infections connected with haemo - both peritoneal dialysis and continuous out-patient peritoneal dialysis.

Route of administration and doses:

Drug is intended for parenteral administration. Before introduction it is recommended to carry out skin test on portability. The dose of drug is established individually depending on severity of a disease, age of the patient, localization of an infection, function of kidneys and sensitivity of the activator.

Solution of drug is entered intravenously (directly into a vein or into a tube of infusional system) or deeply intramusculary into the area of an upper outside quadrant of a big gluteus or into the site of a lateral part of a hip.

Adult appoint 1-6 g of drug a day. Frequency rate введеннь – 2-3 times a day. The maximum daily dose of drug makes 6 g. At a serious illness, especially at patients with reduced immunity (including at patients with a neutropenia) apply 2 g each 8 or 12 hours or to 3 g there are each 12 hours, at infections of urinary tract appoint 0,5-1 g each 12 hours, at the respiratory infections caused by pseudo-monads and at a mucoviscidosis the recommended dose makes 100-150 mg/kg of weight bodies/days for 3 receptions, for prevention of infectious complications at prostate gland operations the drug is administered in a dose 1 g during induction in anesthesia, the following dose is entered during removal of a catheter. At the majority of infections the dose of drug is effective makes 1 g each 8 hours or to 2 g there are each 12 hours.

Duration of treatment makes from 4 to 14 days. It is necessary to continue treatment not less than 48 hours after improvement of a condition of the patient.

To newborns and children aged up to 2 months the recommended dose makes 25-60 mg/kg of body weight a day. The number of introductions – 2 times a day.

To children 2 months drug are more senior appoint in a dose 30-100 mg/kg of body weight a day. Frequency rate of introduction – 2-3 times a day. To children with an immunodeficiency, a mucoviscidosis or meningitis appoint up to 150 mg/kg of body weight a day for 3 receptions (the maximum daily dose – 6 g).

For patients of advanced age, especially for patients 80 years are more senior, the recommended dose of drug makes no more than 3 g a day.

The dosing mode for patients with a renal failure is set depending on values of clearance of creatinine. The initial dose of drug makes 1 g.

Maintenance doses of a ceftazidime at a renal failure are presented in table 1.

Table 1.

Clearance of creatinine (ml/min.)	Concentration of creatinine in serum, µmol/l (mg/l)	The recommended single doses of a ceftazidime
> 50	<150 (<1,7)	Standard doses
50-31	150-200 (1,7-2,3)	1 g each 12 h
30-16	200-350 (2,3-4)	1 g each 24 h
15-6	350-500 (4-5,6)	0,5 g each 24 h
<5	> 500 (> 5,6)	0,5 g each 48 h

Patients with heavy infections can increase a single dose by 50% or to increase the number of inputs of drug. In this case it is necessary to control ceftazidime level in blood serum, concentration of a ceftazidime at the same time should not exceed 40 mg/l.

After each session of a hemodialysis enter maintenance doses of drug according to table 1. At peritoneal dialysis, except intravenous administration, the ceftazidime can be included in dialysis solution (from 125 to 250 mg on 2 l of dialysis solution). For the adults with a renal failure who are on a continuous hemodialysis with use of the arteriovenous shunt and for the patients who are on haemo filtering of high speed in intensive care unit, the recommended dose makes 1 g a day daily (in one or several receptions). For the patients who are on haemo filtering of low speed appoint the recommended doses at a renal failure.

For patients to whom the venovenozna haemo filtering and a venovenozny hemodialysis is carried out recommendations about dosing are provided in tables 2 and 3.

Table 2. Recommendations about dosing of a ceftazidime for patients which carries out long venovenozny haemo filtering.

Residual function of kidneys (clearance of creatinine, ml/min.)	Maintenance dose (mg),  depending on the speed of ultrafiltration (ml/min.) *
	5	16,7	33,3	50
0	250	250	500	500
5	250	250	500	500
10	250	500	500	750
15	250	500	500	750
20	500	500	500	750

* It is necessary to enter a maintenance dose each 12 hours.

Table 3. Recommendations about dosing of a ceftazidime for patients which carries out a long venovenozny hemodialysis.

Rezidualna function of kidneys (clearance of creatinine, ml/min.)	Maintenance dose (mg), depending on the speed of ultrafiltration (ml/min.) *
	1,0 l/h			2,0 l/h
	Speed of ultrafiltration (l/h)			Speed of ultrafiltration (l/h)
	0,5	1,0	2,0	0,5	1,0	2,0
0	500	500	500	500	500	750
5	500	500	750	500	500	750
10	500	500	750	500	750	1000
15	500	750	750	750	750	1000
20	750	750	1000	750	750	1000

* It is necessary to enter a maintenance dose each 12 hours.

Rules of preparation of solution for parenteral administration. Solution is prepared just before introduction. For preparation of solution use 0,9% solution of sodium of chloride, 5% glucose solution, sterile water for an injection. The solvent volume necessary for preparation of solution for parenteral administration depends on amount of drug in a bottle (see tab. 4).

Table 4.

Quantity of a ceftazidime in a bottle	Way введення	Solvent volume	Approximate concentration (mg/ml)
1 g	Intramusculary	3 ml	260
	Intravenously struyno	10 ml	90
	Intravenously in a type of infusion	50 ml	20

For intramuscular introduction bottle contents with 1 g are dissolved in 3 ml of sterile water for injections. After receiving transparent solution if necessary it is possible to part in addition in 2 ml 0,5% or 1% of solution of lidocaine. In case of use of lidocaine it is necessary to carry out skin test on portability of local anesthetics. For intravenous jet administration bottle contents with 1 g are dissolved in 10 ml of water for injections. Solution is entered slowly within 3 - 5 minutes.

For intravenous drop administration of 1 g of drug previously dissolve in 10 ml of water for injections. The received solution in addition part in 50 ml 5% with solution of glucose or isotonic solution of sodium of chloride. Intravenous infusion is carried out at least within 30 min.

The ceftazidime in the form of powder is in a bottle under the lowered pressure. At dissolution of drug carbon dioxide is emitted (in the form of small bubbles) and pressure in a bottle increases. Therefore for the purpose of simplification of use it is recommended to adhere to such method of production of solution for intramuscular or intravenous bolyusny administration:

1) to puncture with the hypodermic needle a cover of a bottle and to enter the recommended amount of solvent,

2) to take out the hypodermic needle and to carefully shake up a bottle within 1 - 2 min. that transparent solution was formed,

3) to turn a bottle. At completely entered piston of the syringe to insert a needle into a bottle cover so that it completely plunged into solution, and to gather all solution in the syringe (the needle has to be submersed in solution).

After dissolution the received solution can have color from light yellow to dark yellow. It depends on storage conditions of drug, its concentration and a type of solvent. At the same time it is necessary to remember that if conditions of cultivation are met, then discoloration of solution will not affect its antibacterial activity.

Features of use:

Use during pregnancy or feeding by a breast. The ceftazidime in a small amount gets into breast milk. For treatment it is necessary to stop feeding by a breast. Use of drug in the I trimester of pregnancy is contraindicated. Use of drug in II and III trimesters of pregnancy is possible only in that case when the potential advantage for mother exceeds possible risk for a fruit.

Children. Drug is used in pediatric practice.

Features of use. At prolonged treatment it is regularly necessary to control functional indicators of a liver, kidneys and bodies of a hemogenesis.

At patients with a renal failure the dose of drug has to be modified depending on degree of manifestation of a renal failure (reduction of a dosage or increase in an interval between administrations of drug).

It is necessary to use with care drug to patients with the burdened allergological anamnesis, and also to patients with the known hypersensitivity to β-laktamny antibiotics as there is a risk of development of cross allergic reactions. In case of allergic reactions it is necessary to stop immediately treatment by drug.

Heavy reactions of hypersensitivity can demand use of adrenaline, a hydrocortisone, antihistaminic drugs and other means of acute management.

Prolonged treatment by drug can lead to development of the infections caused by microflora, resistant to a ceftazidime (for example, Candida, Enterococcus). In that case it is necessary to stop use of drug and/or to appoint the corresponding therapy.

The ceftazidime does not influence results of enzymatic methods of definition of glucose in urine.

With extra care apply a ceftazidime to treatment of newborns.

Ability to influence speed of response at control of motor transport or work with other mechanisms. Special researches on this occasion were not conducted. Considering possible side effects from a nervous system, patients who are treated by a ceftazidime, it is necessary to warn about possibility of side reactions which will negatively influence speed of response during the driving or work with other mechanisms.

Side effects:

From the alimentary system: diarrhea, nausea, vomiting, abdominal pains, increase in activity of transaminases, is rare – stomatitis, colitis, a coloenteritis. As well as at use of other cephalosporins, colitis can be caused by Clostridium difficile and can be shown in the form of pseudomembranous colitis.

Gepatobiliarny reactions: tranzitorny increase in level of one or several liver enzymes (ALT, nuclear heating plant, LDG, GGT, an alkaline phosphatase), is very rare – jaundice.

From system of a hemopoiesis: eosinophilia, thrombocytosis, leukopenia, neutropenia, granulocytopenia, hemolitic anemia, thrombocytopenia.

Allergic reactions: allergic dermatitis, small tortoiseshell, multiformny erythema, fever, Quincke's disease, bronchospasm, Stephens-Johnson's syndrome, toxic epidermal necrolysis, acute anaphylaxis.

From the central nervous system: a headache, dizziness, disturbance of taste, paresthesia, patients with a renal failure at the wrong selection have doses – a tremor, spasms, encephalopathy, a coma.

From an urinary system: an oliguria, increase in content of creatinine and/or urea in blood serum, a renal failure.

Local reactions: phlebitis and thrombophlebitis at intravenous administration, morbidity at intramuscular introduction.

Laboratory indicators: false positive reaction of Koombs, tranzitorny increase in level of urea of blood, an urea nitrogen in blood and/or creatinine in serum.

Approximately at 5% of patients positive reaction of Koombs is observed that can influence blood typing.

Others: seldom – candidiasis, including a mucous membrane of a vagina, aphthous stomatitis.

Interaction with other medicines:

Bacteriostatic antibiotics (chloramphenicol) reduce therapeutic activity

to β-laktamny antibiotics. "Loopback" diuretics (furosemide), aminoglycosides, Vancomycinum, clindamycin reduce clearance of a ceftazidime, in case of simultaneous use that leads to increase in frequency of development of nephrotoxic action.

The ceftazidime is compatible to the majority of solutions for intravenous administration. However the ceftazidime is less stable in sodium bicarbonate solution therefore it is not recommended to be used as solvent.

It is impossible to mix a ceftazidime rolled into one or the syringe with other antibiotics and aminoglycosides.

Contraindications:

Hypersensitivity to components of drug or cephalosporins, penicillin and other β-laktamny antibiotics.

Overdose:

Symptoms: a headache, dizziness, paresthesias, in hard cases – generalized spasms, encephalopathy, a coma.

Treatment: symptomatic and maintenance therapy. At development of spasms – antikonvulsant. At development of reactions of hypersensitivity use of adrenaline, a hydrocortisone, antihistaminic drugs and acceptance of other urgent measures is shown. Concentration of the Ceftazidime in blood serum can be reduced by means of dialysis or peritoneal dialysis.

Storage conditions:

Period of validity - 2 years. To store 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:

On 1 g of drug in a bottle. On 1 bottle in a cardboard box.