Composition, form of production and packaging
Powder for solution for iv and in / m introduction white or white with a yellowish color.
1 f.
ceftazidime pentahydrate 1.165 g,
which corresponds to the content of ceftazidime 1 g
Excipients: sodium carbonate anhydrous - 0.118 g.
1 g - glass bottles (1) - packs of cardboard.
1 g - bottles of glass (10) - packs of cardboard.
1 g - glass bottles (50) - cardboard packs (for hospitals).
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Ceftazidime is a third generation cephalosporin antibiotic 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. In vitro synergism of the action of cefazgidime and aminoglycosides against some strains of microorganisms is observed, as well as additive action.
The prevalence of acquired resistance of bacteria to ceftazidime varies depending on the region and over time, in certain types of microorganisms, resistance can be very high. It is preferable to have local sensitivity data, especially when treating severe infections.
The drug is active in vitro against the following microorganisms:
Bacteria, usually sensitive to ceftazidime:
- Gram-negative aerobes: Haemophillus influenzae 1 , Haemophillus parainfluenzae, Neisseria meningitidis 1 , Neisseria gonorrhoeae, Pasteurella multocida, Proteus mirabilis 1 , Proteus vulgaris 1 , Providencia rettgeri, Salmonella spp., Shigella spp.
- Gram-positive aerobes: Streptococcus pyogenes 1 (group A), Streptococcus agalactiae 1 (gynna B).
Bacteria that are likely to develop acquired resistance:
- Gram-negative aerobes: Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli 1 , Klebsiella spp. (including Klebsiella pneumoniae 1 ), Pseudomonas spp., (including Pseudomonas aeruginosa 1 ), Serratia spp. 1 , Morganella morganii, Yersinia enterocolitica.
- Gram-positive aerobes: Staphylococcus spp. (including Staphylococcus aureus 1 ), Streptococcus pneumoniae 1 . Streptococcus spp. group of viridans.
- Gram-positive anaerobes: Clostridium spp. (not including Clostridium difficile), Peptostreptococcus spp., Propionibacterium spp.
- Gram-negative anaerobes: Fusobacterium spp.
Bacteria that possess natural resistance to ceftazidime:
- Gram-negative aerobes: Campylobacter spp.
- Gram-positive aerobes: Enterococcus spp., including Enterococcus faecalis, Enterococcus faecim, Listeria spp.
- Gram-positive anaerobes: Clostridium difficile.
- Gram-negative anaerobes: Bacteroides spp. including Bacterioides fragilis.
- Other: Chlamydia spp., Mycoplasma spp., Legionella spp.
1 - for these microorganisms, clinical efficacy was shown
PHARMACOKINETICS
The maximum concentration (C max ) of ceftazidime with intramuscular injection of 0.5 g or 1 g is achieved rapidly and correspondingly is 18 Ојg / ml and 37 Ојg / ml.Five minutes after intravenous bolus administration of the drug at a dose of 0.5 g, 1 g or 2 g of C max, respectively, 46 Ојg / ml and 87 Ојg / ml and 170 Ојg / ml. The therapeutic concentration in the blood plasma persists for 8-12 hours after intravenous or intramuscular injection.
After administration, the drug is quickly distributed in the human body and reaches therapeutic concentrations in most tissues and liquids, including synovial, pericardial and peritoneal fluid, as well as in bile, sputum and urine. Distribution also occurs in the bones, myocardium, gall bladder, skin and soft tissues.
Poorly penetrates the intact blood-brain barrier, but with the meningitis achieved by the drug in the cerebrospinal fluid, the therapeutic concentration is 4-20 mg / l.Easily penetrates the placenta and excretes in breast milk. The connection with plasma proteins is less than 10%.
The drug is not metabolized in the liver, a violation of the liver does not affect the pharmacokinetics of the drug.
Half-life with normal kidney function is about 2 hours; in newborns - 3-4 times longer; with hemodialysis - 3-5 hours.
It is excreted unchanged in kidneys to 80-90% during the day by glomerular filtration; with bile - less than 1%.
In case of impaired renal function, a dose reduction is recommended.
INDICATIONS
Infectious-inflammatory diseases caused by microorganisms sensitive to ceftazidime:
- severe infections: peritonitis, septicemia, infections in patients with immunodeficiency, infected burns, severe purulent-septic conditions, meningitis;
- Lower respiratory infections: pneumonia, lung abscess, pleural empyema, infected bronchiectasis (including in patients with cystic fibrosis);
- infections of the ENT organs: otitis media, mastoiditis, sinusitis;
- urinary tract infections: pyelonephritis, pyelitis, prostatitis, cystitis, urethritis, kidney abscess;
- infections of bones and joints: septic arthritis, osteomyelitis, bacterial bursitis;
- skin and soft tissue infections: wound infections, phlegmon, erysipelas, mastitis;
- infections of the gastrointestinal tract, abdominal cavity and biliary tract: retroperitoneal abscesses, cholangitis, gallbladder empyema, cholecystitis, diverticulitis, enterocolitis;
- infections associated with dialysis: hemo- and peritoneal dialysis and continuous ambulatory peritoneal dialysis;
- infections of the pelvic organs: endometritis;
- prevention of infectious complications in operations on the prostate gland.
DOSING MODE
The drug is administered intravenously or intramuscularly. The dose of the drug is determined individually, taking into account the severity of the disease, localization of infection and sensitivity of the pathogen, age and body weight, kidney function.
Adults and children over 12 years of age are prescribed 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. In uncomplicated urinary tract infections - 0.25 g 2 times a day. With complicated infections of the urinary tract - 0.5-1 g 2 times a day.
In cystic fibrosis, patients with respiratory system infections caused by Psedomonas spp. - 30-50 mg / kg 3 times a day (maximum dose of 9 g / day).
In operations on the prostate gland, prophylaxis is administered before the induction of anesthesia, 1 g, the administration is repeated after removal of the catheter.
Children older than 2 months and up to 12 years of age are prescribed 30-100 mg / kg / day (for 2-3 injections), the maximum dose is 6 g / day; children with reduced immunity, cystic fibrosis and meningitis - 150 mg / kg / day in 3 injections, the maximum daily dose is 6 g. Newborns and infants up to 2 months are prescribed 25-60 mg / kg / day in 2 injections.
To elderly patients - considering a possible decrease in creatinine clearance, the recommended dose of ceftazidime should not exceed 3 g / day, especially in patients older than 80 years.
If the kidney function is disturbed, the initial dose is 1 g. The maintenance dose is selected depending on the values ​​of creatinine clearance as indicated below.
Creatinine clearance
31-50 ml / min. 1 g every 12 hours
16-30 ml / min. 1 g every 24 hours
5-15 ml / min 500 mg every 24 hours
<5 mL / min 500 mg 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 blood plasma (should not exceed 40 mg / l).
For children, the clearance of creatinine is calculated in accordance with the ideal body weight or surface area of ​​the body.
Against the background of hemodialysis, maintenance doses are calculated taking into account the clearance of creatinine. the administration is carried out after each hemodialysis session. Against a background of peritoneal dialysis and continuous ambulatory peritoneal dialysis, in addition to intravenous administration, ceftazidime can be included in a 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 on high-speed haemofiltracin 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.
In patients with renal failure who are on hemodialysis or haemofiltration using a veno-venous shunt, the recommended doses are presented in the table below.
Doses of ceftazidime in patients on hemofiltration using a veno-venous shunt
Creatinine clearance, ml / min Maintenance dose (mg) depending on the rate 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
* maintenance dose is administered every 12 hours
Doses of ceftazidime in patients on continuous hemodialysis using a veno-venous shunt
Creatinine clearance, ml / min Maintenance dose (mg) and dependence on dialysis rate *
1.0 l / h 2.0 l / h
Rate of ultrafiltration, l / h Rate 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
* maintenance dose is administered every 12 hours
The duration of treatment with ceftazidime is 7-14 days. In infections caused by Psuedomonas aeruginosa (pneumonia, infectious complications in cystic fibrosis, meningitis), the course of treatment can be increased to 21 days.
Preparation of solutions
1. "Primary" breeding
1.0 g 3 ml water for injection, 0.5% or 1% lidocaine solution with intramuscular injection 10 ml water for injections with intravenous administration
2.0 g 10 ml water for injections with intravenous administration
2. "Secondary" breeding
For intravenous drip introduction, the solution of the preparation prepared in the manner described above is further diluted in 50-100 ml of one of the following solvents intended for intravenous administration:
- 0.9% solution of sodium chloride,
- Hartman's solution,
- 5% and 10% dextrose solution,
- 5% dextrose solution with 0.9% sodium chloride solution.
Use only freshly prepared solution!
SIDE EFFECT
Allergic reactions: urticaria, chills or fever, rash, itching, bronchospasm, eosinophilia, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), angioedema, anaphylactic shock.
On the part of the digestive system: nausea, vomiting, diarrhea, abdominal pain, colitis, dysbiosis, impaired liver function (transient increase in activity of "liver" transaminases, alkaline phosphatase, hyperbilirubinemia), pseudomembranous colitis, jaundice, cholestasis, unpleasant taste in the mouth.
From the hematopoiesis: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, hemolytic anemia, lymphocytosis, hypocoagulation, pancytopenia, aplastic anemia.
From the side of the urinary system: renal dysfunction (azotemia, hypercreatininaemia, increased urea in the blood), toxic nephropathy, interstitial nephritis, acute renal failure, oliguria, anuria.
From the side of the nervous system: headache, dizziness, paresthesia, convulsions, encephalopathy, "fluttering" tremor, coma, neuromuscular excitability, myoclonia.
Local reactions: phlebitis, thrombophlebitis, tenderness along the vein during intravenous administration; morbidity and infiltration at the site of intramuscular injection.
Other: nosebleeds, candidiasis (candidal vaginitis, oropharyngeal candidiasis), superinfection, false positive Coombs test, increased prothrombin time, false positive urine reaction to glucose, lowering of blood pressure.
CONTRAINDICATIONS
- Hypersensitivity to ceftazidime, other components of the drug, other cephalosporins, penicillins.
Carefully
- impaired renal function;
- the period of the newborn;
bleeding history;
- colitis in the anamnesis;
- Malabsorption syndrome (increased risk of decreased prothrombin activity, especially in patients with severe renal and / or liver failure);
- a combination with loop diuretics, aminoglycosides.
PREGNANCY AND LACTATION
Use in pregnancy is possible only in cases where the intended benefit to the mother exceeds the potential risk to the fetus.
If you need to use the drug during lactation, you should decide whether to stop breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
If the kidney function is disturbed, the initial dose is 1 g. The maintenance dose is selected depending on the values ​​of creatinine clearance as indicated below.
Creatinine clearance
31-50 ml / min. 1 g every 12 hours
16-30 ml / min. 1 g every 24 hours
5-15 ml / min 500 mg every 24 hours
<5 mL / min 500 mg every 48 hours
APPLICATION FOR CHILDREN
Children are prescribed according to the indications in accordance with the dosing regimen. With care to newborn children
APPLICATION IN ELDERLY PATIENTS
To elderly patients - considering a possible decrease in creatinine clearance, the recommended dose of ceftazidime should not exceed 3 g / day, especially in patients older than 80 years.
SPECIAL INSTRUCTIONS
Before starting treatment with the drug, you need to collect a detailed history of previous reactions of hypersensitivity to ceftazidime, cephalosporins, penicillins and other drugs. In 3-7% of patients with an allergy to penicillins, a history of cross-sensitivity to cephalosporins was noted. When developing allergic reactions to ceftazidime, the drug should be immediately discontinued, in severe cases, epinephrine, glucocorticosteroid hormones, antihistamines or other emergency measures may be required. The simultaneous use of cephalosporins with nephrotoxic drugs, such as aminoglycosides, diuretics (furosemide), may lead to an increased risk of nephrotoxic action.
Since ceftazidime is excreted by the kidneys, in patients with impaired renal function, its dose should be reduced in accordance with the degree of impairment.
Ceftazidime may interfere with the synthesis of vitamin K due to suppression of the intestinal microflora, which can cause a decrease in the level of vitamin K-dependent clotting factors, and in rare cases lead to hypothrombinemia and bleeding. In elderly and weakened patients, in patients with impaired liver function and in persons with malnutrition, the risk of developing bleeding is highest. In such patients, prothrombin time should be monitored. The appointment of vitamin K eliminates hypothrombinemia.
Some patients may develop pseudomembranous colitis during or after the administration of ceftazidime, caused by toxins produced by Clostridium difficile. The degree of severity can range from mild to life-threatening. Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after use of the drug. In mild cases, it is sufficient to cancel the drug, and in more severe cases it is recommended to restore the water-salt and protein balance; prescribe metronidazole, bacitracin or vancomycin. The use of drugs that inhibit intestinal peristalsis is contraindicated.
Prolonged use of broad-spectrum antibacterial drugs, including ceftazidime, can lead to an increase in the growth of insensitive microorganisms (eg, Enterococci, Candida), and treatment may need to be discontinued or appropriate therapy taken. During treatment it is necessary to constantly assess the patient's condition.
As with other beta-lactam antibacterials of a wide spectrum of action, with the use of ceftazidime in some initially sensitive strains of microorganisms (for example, Enterobacter spp., Pseudomonas spp., Serratia spp.) Resistance can develop. Therefore, in the treatment of infections caused by these microorganisms, periodic studies should be conducted on the sensitivity to antibacterial drugs.
Possible false positive Coombs test and a false positive urine reaction to glucose (Benedict test, Feling, Clinintest).
Ceftazidime does not affect the quantitative determination of creatinine by the alkaline-picrate method.
During treatment, ethanol can not be used because of the possibility of disulfiram-like reactions (sudden "tide" of blood to the face, spastic abdominal pain, nausea, vomiting, headache, tachycardia, shortness of breath).
Influence on ability to drive vehicles, mechanisms
Care should be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
OVERDOSE
Symptoms: dizziness, paresthesia, headache, convulsions, deviations in the results of laboratory tests.
Treatment: since there is no specific antidote, the treatment is symptomatic and supportive. Concentration of ceftazidime in the blood can be reduced by hemodialysis.
DRUG INTERACTION
Pharmacologically incompatible with aminoglycosides (significant mutual inactivation: with simultaneous use these drugs should be administered to different parts of the body), vancomycin (forms a precipitate depending on the concentration, if necessary, administer two drugs through a single tube, between their use, the intravenous system should be rinsed) .
Do not use sodium bicarbonate solution as a solvent! Pharmaceutically compatible with the following solutions: at a concentration of 1 to 40 mg / ml - 0.9% solution of sodium chloride; sodium lactate solution; Hartman's solution; 5% dextrose solution; 0.225% sodium chloride solution and 5% dextrose solution; 0.45% sodium chloride solution and 5% dextrose solution: 0.9% sodium chloride solution and 5% dextrose solution; 0.18% sodium chloride solution and 4% dextrose solution; 10% dextrose solution; 10% dextran solution with a molecular weight of 40 thousand daltons in a 0.9% solution of sodium chloride or in a 5% solution of dextrose; 6% dextran solution with a molecular weight of 70 thousand daltons in a 0.9% solution of sodium chloride or in a 5% solution of dextrose.
At a concentration of 0.05 to 0.25 mg / ml, ceftazidime is compatible with the solution for intraperitoneal dialysis (lactate).
For intramuscular administration, ceftazidime can be diluted with a solution of lidocaine hydrochloride 0.5% or 1% (for adults).
If ceftazidime at a concentration of 4 mg / ml is added to the following solutions, both components retain activity: hydrocortisone 1 mg / ml in a 0.9% solution of sodium chloride or in a 5% solution of dextrose: cefuroxime (cefuroxime sodium) 3 mg / ml in 0 , 9% sodium chloride solution: cloxacillin (cloxacillin sodium) 4 mg / ml in 0.9% sodium chloride solution; 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 the ceftazidime solution (500 mg in 1.5 ml water for injection) and metronidazole (500 mg / 100 ml) both components retain their activity.
"Loop" diuretics, aminoglycosides, vancomycin, clindamycin reduced clearance of ceftazidime, resulting in increased risk of nephrotoxicity. Bacteriostatic antibiotics (including chloramphenicol) reduce the effectiveness of the drug. Ceftazidime may disrupt the intestinal microflora, which may lead to a decrease in reabsorption of estrogens and decrease the efficiency of combined oral contraceptives.
TERMS OF RELEASE FROM PHARMACY
Prescription.
TERMS AND CONDITIONS OF STORAGE
In the dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life - 3 years. Do not use the drug after the expiration date.
