Ceftazidime - instructions for use, doses, side effects, contraindications

Cephalosporin antibiotic III generation for parenteral use. It acts bactericidal (it breaks the synthesis of the cell wall of microorganisms). Has a wide range of action. Resistant to the action of most beta-lactamases. Effects on many strains resistant to ampicillin and other cephalosporins. Active against gram-negative microorganisms: Pseudomonas spp., including Pseudomonas aeruginosa, Klebsiella spp., including Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Escherichia coli, Enterobacter spp., including Enterobacter aerogenes, Enterobacter cloacae, Citrobacter spp., including Citrobacter diversus, Citrobacter freundii, Pasteurella multocida, Neisseria meningitidis, Haemophilus influenzae (including strains resistant to ampicillin); Gram-positive microorganisms: Staphylococcus aureus (penicillinase-producing and penicillinase-producing strains sensitive to methicillin), Streptococcus pyogenes (group A beta-hemolytic streptococcus), Streptococcus agalactiae (group B), Streptococcus pneumoniae, anaerobic microorganisms: Bacteroides spp. (many strains Bacteroides fragilis resistant).

Inactive with respect to methicillin-resistant Staphylococcus spp., Streptococcus faecalis, Enterococcus spp., Listeria monocytogenes, Campylobacter spp. and Clostridium difficile.

Active in vitro against majority strains the following organisms: Clostridium perfringens, Acinetobacter spp., Haemophilus parainfluenzae, Morganella morganii, Neisseria gonorrhoeae, Peptococcus spp., Peptostreptococcus spp., Providencia spp., at Tom number of, Providencia rettgeri, Salmonella spp., Shigella spp., Staphylococcus epidermidis, Yersinia enterocolitis.

Pharmacokinetics:

Maximum concentration in blood plasma (C_max) after intramuscular (IM) administration, 1 g - 39 mg / l, time to reach the maximum concentration in the blood plasma (TS_max) - 1 h. From_max after intravenous (iv) bolus administration in doses of 1 g and 2 g - 69 mg / l and 170 mg / l, respectively. Therapeutically effective serum concentrations persist, 8-12 hours after IV and IM. The connection with plasma proteins is less than 10%. Concentrations of ceftazidime exceeding the minimum inhibitory concentration (MIC) for mostprevalent pathogenic microorganisms, can be achieved in bone tissue, heart, bile, sputum, synovial fluid, intraocular, pleural and peritoneal fluids. Easily penetrates the placenta and excretes in breast milk. In the absence of an inflammatory process, it does not penetrate poorly through blood-brain barrier. When meningitis, the concentration in the cerebrospinal fluid reaches a therapeutic value (4-20 mg / L and higher). The half-life (T1 / 2) is 1.9 hours, in newborns 3-4 times longer; with hemodialysis - 3-5 hours. It is not metabolized in the liver. It is excreted by the kidneys (80-90% unchanged by glomerular filtration) for 24 hours; with bile - less than 1%.

Indications:Infectious-inflammatory diseases caused by susceptible to ceftazidime pathogens:

- severe infections, including nosocomial infections (septicemia, bacteremia, peritonitis, meningitis, infections in patients with immunodeficiency, including those with neutropenia);

- infections of the respiratory tract (including, in patients with cystic fibrosis);

- infection of LOP-organs;

- urinary tract infections;

- infections of the skin and soft tissues;

- infections of the gastrointestinal tract (GIT), biliary tract and abdominal cavity;

- infection of bones and joints;

- infectious complications of hemodialysis and peritoneal dialysis, including in patients on continuous ambulatory peritoneal dialysis;

- preventive maintenance of infectious complications at operations on a prostate gland (transurethral resection).

Contraindications:Hypersensitivity to ceftazidime, penicillins, other cephalosporins and beta-lactam antibiotics or excipients included in the preparation.

Carefully:Renal insufficiency, diseases of the digestive tract (including ulcerative colitis in the anamnesis), malabsorption syndrome, simultaneous administration with loop diuretics and aminoglycosides, neonatal period.

Pregnancy and lactation:

Pregnancy: experience with the drug in pregnant women is limited. Given that ceftazidime, like most other cephalosporins, penetrates the placenta, the drug should be used in pregnant women only in cases of vital necessity, with careful evaluation of the consequences of treatment in terms of possible risk to the fetus and benefit to the mother.

Lactation: The decision to discontinue the drug during breastfeeding should also be taken on the basis of an assessment of the relationship between benefit to the mother and the risk to the child. In a child with breast-feeding in this case, diarrhea may develop and fungal infection with mucosal lesions requiring refusal of breastfeeding, as well as allergic reactions to ceftazidime.

Dosing and Administration:

In / in or / m.

In adults and children over 12 years of age apply 1 g every 8-12 hours or 2 g at intervals of 12 hours. In severe infections, especially in patients with reduced immunity (including patients with neutropenia), 2 g every 8 hours or 3 g every 12 hours.

With complicated infections of the urinary tract - 0.5 -1 g 2 times a day.

In uncomplicated urinary tract infections - 0.25 g 2 times a day.

In cystic fibrosis, patients with respiratory system infections caused by Pseudomonas spp. - 30-50 mg / kg every 8 hours.

In case of prostate surgery, 1 g of the drug is administered before the initial anesthesia, the introduction is repeated after removal of the catheter. In elderly patients, the maximum daily dose should not exceed 3 g.Children from 2 months to 12 years of age use 30-100 mg / kg / day (2-3 injections); children with reduced immunity, cystic fibrosis and meningitis - 150 mg / kg / day in 3 injections, the maximum daily dose - 6 g.

In newborns and infants up to 2 months of age, 25-60 mg / kg / day in 2 injections are used. If the renal function is impaired, the initial saturating dose is 1 g. The maintenance dose is selected depending on the rate of excretion: for creatinine clearance (CK) 50-31 ml / min -1 g 2 times a day, 30-16 ml / min -1 g 1 once a day, 15-5 ml / min - 0.5 g once a day; less than 5 ml / min - 0.5 g once every 48 hours.

For patients with severe infections, a single dose can be increased by 50%, while they should control the concentration of ceftazidime in the serum (should not exceed 40 mg / l).

Against the background of hemodialysis, maintenance doses are calculated taking into account QC, the administration is performed after each hemodialysis session. Against the background of peritoneal dialysis, in addition to intravenous administration ceftazidime can be included in the dialysis solution (125-250 mg per 2 liters of dialysis solution). In patients with renal insufficiency, on continuous hemodialysis using an arteriovenous shunt, and in patients who are on high-speed haemofiltration in the intensive care unit, the recommended dose is 1 g / day daily (for one or more injections).

Patients on low-speed haemofiltration use doses recommended for renal dysfunction.

The duration of the course of therapy is 7-14 days. In severe infections (pneumonia, purulent complications of cystic fibrosis, meningitis), the course of treatment can be increased to 21 days.

Rules for the preparation of solution for injection. For intramuscular administration, ceftazidime powder is dissolved in 3 ml of the solvent, for IV bolus administration in 10 ml, for IV drip in 50 ml. In the prepared solution, small bubbles of carbon dioxide may be present, which does not affect the effectiveness of the preparation. Light yellowing of the solution does not affect the efficiency. Store the reconstituted solution at 2-8 ° C for a maximum of 24 hours.

Ceftazidime is pharmaceutically compatible with the following solutions: at a concentration of 1 to 40 mg / ml - 0.9% sodium chloride solution, sodium lactate solution, Hartman solution, 5% dextrose solution; 0.225% sodium chloride solution and 5% dextrose solution; 0.45% sodium chloride solution and 5% dextrose solution; 0.9% solution of sodium chloride and 5% solution of dextrose; 0.18% sodium chloride solution and 4% dextrose solution; 10% dextrose solution; 10 %a solution of dextran with a molecular weight of about 40,000 Da in a 0.9% solution of sodium chloride or in a 5% solution of dextrose; 6% dextran solution with a molecular weight of about 70,000 Da in a 0.9% solution of sodium chloride or in a 5% solution of dextrose.

In concentrations from 0.05 to 0.25 mg / ml ceftazidime compatible with the solution for intraperitoneal dialysis (lactate).

For the / m introduction ceftazidime can be diluted with water for injection or 0.5-1% solution of lidocaine hydrochloride.

Both components remain active if ceftazidime in a concentration of 4 mg / ml is added to the following solutions: hydrocortisone (hydrocortisone sodium phosphate) 1 mg / ml in a 0.9% solution of sodium chloride or 5% solution of dextrose; cefuroxime (cefuroxime sodium) 3 mg / ml in a 0.9% solution of sodium chloride; cloxacillin (cloxacillin sodium) 4 mg / ml in a 0.9% solution of sodium chloride; heparin 10 IU / ml or 50 IU / ml in a 0.9% solution of sodium chloride; potassium chloride 10 mEq / L or 40 mEq / L in a 0.9% solution of sodium chloride. When mixing ceftazidime solution (500 mg in 1.5 ml of water for injection) and metronidazole (500 mg / 100 ml), both components remain active.

Side effects:

Allergic reactions: urticaria, fever, eosinophilia, itchy skin, spotty-papular rash,toxic epidermal necrolysis (Lyell's syndrome), multiforme exudative erythema (including Stevens-Johnson syndrome), angioedema, anaphylactic reactions, anaphylactic shock, bronchospasm, lowering of blood pressure.

Local reactions: when in / in the introduction - phlebitis or thrombophlebitis, pain and inflammation; with the / m introduction - soreness, burning, compaction at the injection site.

From the nervous system: headache, dizziness, paresthesia, disorders

of consciousness, a violation of taste perception, spasms, in patients with impaired renal function with improper dose selection - convulsions, encephalopathy, fluttering tremor, coma, neuromuscular excitability.

From the genitourinary system: candidiasis vaginitis, impaired renal function, decreased glomerular filtration, toxic nephropathy.

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, pseudomembranous colitis, cholestasis, candidiasis of the oral mucosa, jaundice. From the hematopoiesis: leukopenia, neutropenia, thrombocytopenia, thrombocytosis, agranulocytosis, lymphocytosis, hemolytic anemia, hemorrhages. Laboratory indicators: hypercreatininaemia, azotemia, increased urea concentration, false positive urine reaction to glucose, increased activity of "hepatic" transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT), gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase), hyperbilirubinemia, false-positive direct Coombs test without hemolysis, increased prothrombin time, pancytopenia.

Other: "tides".

Overdose:

It often occurs in patients with renal insufficiency.

Symptoms: dizziness, paresthesia, headache, a deviation in the results of laboratory tests (increase in urea and serum creatinine in the blood, hyperbilirubinemia, thrombocytosis, thrombocytopenia, eosinophilia, leukopenia, prolongation of prothrombin time), in patients with renal insufficiency-convulsions, encephalopathy, fluttering "tremor, coma, neuromuscular excitability.

An overdose of ceftazidime can cause pain, inflammation, phlebitis at the site of infusion. Since there is no specific antidote, treatment is symptomatic and supportive, measures aimed at controlling seizures are also needed.In patients with impaired renal function, and also in case of severe overdose, when conservative therapy is unsuccessful, the concentration of ceftazidime in the blood can be reduced by peritoneal dialysis.

Interaction:

Pharmacologically incompatible with aminoglycosides (significant mutual inactivation: with simultaneous use these drugs should be injected into different parts of the body) and vancomycin (forms a precipitate depending on the concentration, if necessary, administer two drugs through one port of the catheter, between their use of the system for intravenous administration should be washed ). Do not use sodium bicarbonate solution as a solvent.

"Loop" diuretics, aminoglycosides, vancomycin, clindamycin reduce clearance, which increases the risk of nephrotoxic action.

Bacteriostatic antibiotics (incl. chloramphenicol) reduce the effectiveness of the drug.

Special instructions:

Patients who had a history of allergic reactions to penicillins, may have increased sensitivity to cephalosporin antibiotics.

Against the background of the use of ceftazidime, cases of development of antibiotic-associated diarrhea, colitis and pseudomembranous colitis caused by Clostridium difficile. These conditions should be included in the diagnostic search if the patient develops diarrhea on the background or soon after the completion of the course of antibiotic therapy. Development during the period of ceftazidime therapy of severe or bloody diarrhea is an indication for the abolition of the antibiotic and the beginning of appropriate treatment. Drugs that slow the peristalsis of the intestine are contraindicated.

With the simultaneous use of cephalosporins in a high dose with nephrotoxic drugs, such as aminoglycoside antibiotics and diuretics (for example, furosemide), it is necessary to monitor kidney function.

Patients with acute and chronic renal failure need dose adjustment of ceftazidime in view of the risk of developing clinically relevant disorders, for example, seizures (see section "Dosing and Administration").

When undertaking a prolonged course of ceftazidime, regular blood testing is recommended to assess liver and kidney function. As with other cephalosporins, prolonged therapy with ceftazidime may be accompanied by an excess of insensitive microorganisms, such as Enterococci, Candida and Serralia spp.

Ceftazidime has no effect on the results of enzymatic tests for the determination of glucose in the urine, but it may have little effect on the results of the tests based on the reduction of copper (Benedict's test, Feling, Klinist). Ceftazidime does not affect the results of the test for determination of creatinine content based on alkaline picrate.

A false positive Coombs test is noted in approximately 5% of cases of ceftazidime.

During treatment can not be used ethanol because of the possibility of development of disulfiram-like reactions.

In the vial of ceftazidime, 1.0 mg contains 54 mg (2.3 mmol) of sodium. This information should be taken into account when using the drug in patients who adhere to a diet that restricts sodium intake.

Effect on the ability to drive transp. cf. and fur:Studies to study the effect of ceftazidime on the ability to drive a car and work with mechanisms have not been carried out. However, caution should be exercised when driving and working with machinery, as the drug may cause dizziness, convulsions and other side effects that may affect these abilities.

Form release / dosage:

Powder for the preparation of solution for intravenous and intramuscular injection, 1000 mg.

Packaging:For 1000 mg of the drug in a bottle of colorless glass type III with a capacity of 20 ml, ukuporenny brombutilovoy stopper gray and rolled with an aluminum cap type flip-off orange.

1 bottle with instructions for use in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. The reconstituted solution should be stored at a temperature of 2 - 8 ° C not more than 24 hours.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date. Shelf life of the reconstituted solution is no more than 24 hours.

Terms of leave from pharmacies:On prescription

Registration number:LP-001425

Date of registration:12.01.2013

Date of cancellation:2018-01-12

The owner of the registration certificate:Aurobindo Pharma Co., Ltd.Aurobindo Pharma Co., Ltd. India

Manufacturer: & nbsp

AUROBINDO PHARMA, Ltd. India

Representation: & nbspAurobindo Pharma, ZAOAurobindo Pharma, ZAO

Information update date: & nbsp07.11.2015

Illustrated instructions

Instructions

Ceftazidime (Ceftazidime)