Orzid

General characteristics. Structure:

Active ingredient: 250 mg, 500 mg or 1000 mg of a ceftazidime (in the form of pentahydrate).

Excipients: sodium carbonate.

Pharmacological properties:

Pharmacodynamics. Orzid — a tsefalosporinovy antibiotic ІІІ generations. It has bactericidal effect at the expense of inhibition of synthesis of a cell wall of bacteria. The ceftazidime acetylates membrane-bound transpeptidases, increasing thus formation of cross bonds in the peptidoglikanovy chains necessary for ensuring durability and rigidity of a cell wall.

Has a wide range of antimicrobic action. It is active rather various aerobic and anaerobic gram-positive and gram-negative bacteria, including:

- sensitive (aerobic gram-positive bacteria) — Staphylococcus aureus (the strains sensitive to Methicillinum), Staphylococcus epidermidis (the strains sensitive to Methicillinum), Micrococcus spp., Streptococcus pyogenes (a hemolitic streptococcus of group A), Streptococcus of group In (Streptococcus agalactiae), Streptococcus pneumoniae, Streptococcus mitis, Streptococcus spp. (except for Streptococcus faecalis);

- sensitive (aerobic gram-negative bacteria) — Pseudomonas aeruginosa, Pseudomonas spp. (including Pseudomonas pseudomallei), Klebsiella spp. (including Klebsiella pneumoniae), Proteus mirabilis, 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);

- sensitive (anaerobic gram-positive bacteria) — Peptococcus spp., Peptostreptococcus spp., Streptococcus spp., Propionibacterium spp., Clostridium perfringers, Fusobacterium spp., sensitive (anaerobic gram-negative bacteria) — Fusobacterium spp., Bacteroides spp. (many strains of Bacteroides fragilis are resistant);

- resistant (aerobic gram-positive bacteria — metitsillinrezistentny staphylococcus, Streptococcus faecalis and many other Enterococci, Listeria monocytogenes; resistant (aerobic gram-negative bacteria) — Campylobacter spp. and Clostridium difficile.

Drug is effective at treatment of the diseases caused by a pyocyanic stick.

Pharmacokinetics. In 5 min. later in/in introductions of one dose of 500 mg and 1 g peak concentration of drug in a blood plasma makes 45 and 90 mkg/ml respectively. After introduction of one dose in oil of 500 mg and 1 g peak concentration of drug in a blood plasma makes 18 and 37 mkg/ml respectively. At in injection for 30 min. one dose of 500 mg and 1 g peak concentration of drug in a blood plasma makes 42 and 69 mkg/ml respectively.

After introduction drug is quickly distributed in a human body and reaches therapeutic concentration in the majority of fabrics and liquids, including synovial, pericardiac and peritoneal fluid, and also in bile, a phlegm and urine. Distribution also happens in bones, a myocardium, a gall bladder, skin and soft tissues in the concentration sufficient for treatment of infectious diseases, especially at inflammatory processes which strengthen drug diffusion.

Drug badly gets through the unimpaired GEB, but therapeutic level of concentration which is reached in SMZh, is sufficient for treatment of meningitis. Oborotno contacts proteins of a blood plasma (<10%), and bactericidal action shows only in a free look. Level of proteinaceous binding does not depend on concentration. Therapeutic concentration in a blood plasma remains for 8-12 the p. T1/2 at normal renal function — 1,8 h; at broken — 2,2 h. Drug is not metabolized in a liver. Patients with the broken function of a liver have a pharmacodynamics and pharmacokinetics of drug do not change therefore there is no need to adjust a dose. Drug in not changed look with kidneys — to 80–90% (70% of the entered dose for the first 4 h) for days by glomerular filtering and canalicular secretion is emitted. At a renal failure it is recommended to lower a dose. The volume of distribution makes 0,21–0,28 l/kg. Drug collects in soft tissues, kidneys, lungs, bones and joints, serous cavities. Newborns have duration of T1/2 more, than at adults by 3–4 times.

Indications to use:

The infectious and inflammatory diseases of a heavy current caused by microorganisms, sensitive to drug, including:

• sepsis:
• meningitis, including at newborns;
• infections of a GIT, abdominal cavity and bilious ways (peritonitis, coloenteritis, peritoneal abscesses, diverticulitis, inflammation of bodies of a small pelvis, cholecystitis, cholangitis, empyema of a gall bladder);
• infections of female generative organs;
• disease of an ear, throat, nose (mastoiditis, average otitis);
• infections of kidneys and urinary tract, including pyelonephritis, pyelitis, prostatitis, cystitis, urethritis (only bacterial), kidney abscess;
• infections of bones, joints, skin and soft tissues (skin ulcer, phlegmon, ugly face, contaminated wounds and burns);
• respiratory infections (especially pneumonia, and also abscess of lungs, pleura empyema);
• mucoviscidosis.

Infectious processes which arose owing to carrying out a hemodialysis and peritoneal dialysis. A serious infectious and inflammatory illness at patients with reduced immunity.

Prevention of infectious complications at prostate gland operations (a transurethral resection).

Route of administration and doses:

the ceftazidime is applied only parenterally (in/in or in oil). The dose of drug is established individually, taking into account disease severity, by localizations of an infection and sensitivity of the activator, age and body weight, function of kidneys.

Dose for adults — 1–6 g/days. The maximum daily dose — 6 g. At uncomplicated infections of urinary tract in/in or in oil — on 250 mg in 12 h.

At a heavy infection of urinary tract in oil or in/in — 500 mg (1 g) each 12 h.

At the majority of infections an effective dose of 500 mg — 1 g each 8 h or 2 g each 12 h. At a severe disease, especially patients with reduced immunity have 2 g in each 8 or 12 h.

At infections of bones and joints — in/in on 2 g each 12 h. An adult, sick mucoviscidosis, at the respiratory infections caused by Pseudomonas spp. —   from 100 to 150 mg/kg/days, frequency rate of introduction — 3 times a day. The maximum daily dose — 9 g.

Doses for children: children aged up to 2 months — 25–50 mg/kg/days for 2 introductions; children are more senior than 2 months — 30–100 mg/kg/days for 2 or 3 introductions. To children with reduced immunity, a mucoviscidosis, meningitis — to 150 mg/kg/days (at most 6 g/days) for 3 introductions. The maximum daily dose for children should not exceed 6 g.

Doses for patients of advanced age: the recommended daily dose of a ceftazidime should not exceed 3 g.

Drug dosing at patients with a renal failure. The initial dose makes 1 g. The maintenance dose is selected according to a glomerular filtration rate.

Recommendations concerning a correcting of doses for patients with clearance of creatinine <50 ml/min. are given in the table below.

Clearance of creatinine, ml/min.	Dose on one introduction ( on the basis of a dose of 250 mg, either 500 mg, or 1 g)	Frequency
50–31	1 g	Each 12 h
30–16	1 g	Each 24 h
15–6	500 mg	Each 24 h
<5	500 mg	Each 48 h

For children the clearance of creatinine is calculated proceeding from body weight, by body surface areas. For patients who are on a hemodialysis the shock dose makes 1 g and on 1 g after each session of a hemodialysis. For the patients who are on peritoneal dialysis, the shock dose makes 1 g and 500 mg each 24 h.

Recommendations concerning preparation of solution are given in the table below.

Way of introduction, dose	Solvent volume for cultivation, ml	The approximate volume of the received solution, ml	Approximate concentration of a ceftazidime, mg/ml
250 mg in oil	1,0	1,2	210
500 mg in oil	1,5	1,8	280
1000 mg in oil	3	3,6	280
250 mg in oil	2,5	2,7	100
500 mg in oil	5	5,3	100
1000 mg in oil	10	10,6	100
In/in infusion of 1000 mg	50 *	53,0	20

* Dissolve solution in 2 receptions. Prepost the skin sensitivity test to an antibiotic. For in oil or in/in bolyusny introductions dissolve drug in 3 ml of sterile water for injections for 1  (in oil) or in 10 ml of sterile water for injections on 1 g (in/in). The bottle needs to be stirred up. At in/in an injection solution is entered deeply into a big sedalishchy muscle or into the front surface of a hip. Into drug it is entered slowly, for 3–5 min.

For in/in infusion drug at first dissolve in water for injections in the ratio 1 g:10 ml, and then dilute in 50 ml of stated below solvents: 0,9% chloride sodium solution; ^1/6  mol sodium lactate solution; 5% glucose solution; 5% solution of glucose and 0,225% chloride sodium solution; 5% solution of glucose and 0,45% chloride sodium solution; 5% solution of glucose and 0,9% chloride sodium solution; 10% glucose solution. In/in infusion not less than 30 min. are spent.

Solution may contain several vials of carbon dioxide. These solutions are stable for 18 h at the room temperature or 7 days in the refrigerator (5 °C). Easy yellowing of solution  does not influence efficiency of drug.

To apply only freshly cooked solution!

Features of use:

At a renal failure, and also correction of the mode of dosing depending on indicators of clearance of creatinine is necessary for the patients who are on a hemodialysis.

With care apply in the presence at patients with a complication of gastrointestinal diseases in the anamnesis, especially with chronic colitis.

Use during pregnancy and feeding by a breast. Safety of use of the drug Orzid® during pregnancy was not studied. To pregnant women drug is appointed according to vital indications or if the expected advantage for mother exceeds potential risk for a fruit. For drug use feeding by a breast needs to be stopped.

Influence on ability to drive the car or to work with difficult mechanisms. There are no data, however it is supposed that Orzid should not influence ability to drive the car or to work with difficult mechanisms.

Side effects:

Allergic reactions (urticaria, eosinophilia, itch, fever); nausea, vomiting, diarrhea, stomach ache, colitis; candidiasis; dizziness, headache, paresthesia: increase in activity of hepatic transaminases, hyperazotemia, hypercreatinemia, increase in content of urea, leukopenia, neutropenia, thrombocytopenia, lymphocytosis; Quincke's edema, acute anaphylaxis.

At in introduction — phlebitis; at introduction in oil — morbidity, burning, consolidation in the place of an injection.

Interaction with other medicines:

Orzid's mixing with aminoglikozidny antibiotics can lead to a considerable mutual inactivation. At their co-administration the drugs need to be administered in different parts of a body.

Mixing of solution of Orzid in one syringe or in one capacity (a bottle, etc.) which are intended for in/in introductions with these antibiotics is not allowed.

Vancomycinum is incompatible with Orzid and regardless of concentration the deposit can appear. In need of administration of these two drugs through one tube it is necessary to wash out between their introduction system (device) for in/in introductions.

At co-administration of tsefalosporinovy antibiotics with nephrotoxic drugs, for example, (furosemide), danger of increase in nephrotoxicity, especially at patients with a renal failure exists loopback diuretics.

Contraindications:

Hypersensitivity to cephalosporins and another beta лактамным to antibiotics, І a pregnancy trimester, the feeding period a breast.

Overdose:

Symptoms: dizziness, paresthesia, headache, spasms.

Treatment: there is no specific antidote, a symptomatic treatment. Concentration of drug in blood can be reduced by means of a hemodialysis.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. Freshly cooked solution is suitable for use for 18 h at a temperature not above 25 °C or 7 days in the refrigerator.

Issue conditions:

According to the recipe

Packaging:

250 mg, 500 mg or 1000 mg - bottles (1) - packs cardboard.
250 mg, 500 mg or 1000 mg - bottles of colourless glass (1) - a pack cardboard.