Ceftazidime-Vial - instructions for use, dose, side effects, contraindications

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 ceftazidime and aminoglycosides with respect to certain 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 influenzae¹, Haemophilus parainfluenzae, Neisseria meningitidi¹, Neisseria gonorrhoeae, Pasteurella multocida, Proteus mirabilis¹, Proteus vulgaris¹, Providencia rettgeri, Salmonella spp., Shigella spp.

- Gram-positive aerobes: Streptococcus pyogenes¹ (Group A), Streptococcus agalactiae¹(group B).

Bacteria that are likely to develop acquired resistance:

- gram-negative aerobes: Acinetobacter spp., Citrobacter spp.¹, Enterobacter spp.¹, Escherichia coli¹, Klebsiella spp. (at Tom number of Klebsiella pneumoniae^l), Pseudomonas spp., (including Pseudomonas aeruginosa¹), Serratia spp.¹,Morganella morganii, Yersinia enterocolitica.

- gram positive aerobes: Staphylococcus spp. (including Staphylococcus aureus¹), Streptococcus pneumoniae¹,Streptococcus spp. groups 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 Bactericidesfragilis.

- other: Chlamydia spp., Mycoplasma spp., Legionella spp.

¹ - for these microorganisms was shown clinical effectiveness

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 μg / ml and 37 μg / 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 μg / ml and 87 μg / ml and 170 μg / ml. The therapeutic concentration in the blood plasma is maintained 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.

Poor penetration through intact blood-brain barrier, but with 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 tract infections: pneumonia, lung abscess, pleural empyema, infected bronchiectasis (including in patients with cystic fibrosis).

Infections of 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.

Infections of the skin and soft tissues: 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.

Contraindications:Hypersensitivity to ceftazidime, other components of the drug, other cephalosporins, penicillins.

Carefully:impaired renal function; the period of the newborn; hemorrhages in the anamnesis; colitis in history; malabsorption syndrome (increased risk of decreased prothrombin activity, especially in patients with severe renal and / or liver failure); 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.

Dosing and Administration:

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 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 infections caused by Pseudomonas 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 over 2 months. and up to 12 years appoint 30-100 mg / kg / day (for 2-3 injections), the maximum dose - 6 g / day; children with reduced immunity, cystic fibrosis and meningitis - 150 mg / kg / day in 3 injections, the maximum daily dose - 6 g.

Newborns and infants under 2 months of age. prescribe 25-60 mg / kg / day in 2 injections.

To patients of advanced age - Considering the 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 the clearance of kirensacreatinin as indicated below.

CREATINE CREATININE	DOSE
31-50 ml / min.	1 g every 12 h
16-30 ml / min.	1 g every 24 h
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 performed 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 the dialysis solution (125-250 mg per 2 liters of dialysis solution). In patients with renal failure who are on continuous hemodialysis using an arteriovenous shunt,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.

In patients with renal failure who are on hemodialysis or haemofiltration using a veno-venous shunt, the recommended dose are presented in the table below.

Doses of ceftazidime in patients on hemofiltration using a venovenous 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

Clearance creatinine, ml / min	Maintenance dose (mg) depending on the rate of dialysis *
	1.0 l / h			2.0 l / h
	The 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 Pseudomonas aeruginosa (pneumonia, infectious complications of cystic fibrosis, meningitis) treatment course can be increased up to 21 days.

Preparation of solutions

1. "Primary" breeding

1.0 g	3 ml of water for injection, 0.5% or 1% solution of lidocaine with intramuscular injection.	10 ml of water for injection with intravenous injection.
2.0 g		10 ml of water for injection with intravenous injection.

2. "Secondary" breeding

Day of intravenous drip The preparation solution obtained by the above described method 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 effects:

Allergic reactions: urticaria, chills or fever, rash, itching, bronchospasm, eosinophilia, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), angioedema, anaphylactic shock.

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, colitis, dysbiosis, impaired liver function (transient increaseactivity 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 urinary system: renal dysfunction (azotemia, hypercreatininaemia, increased urea in the blood), toxic nephropathy, interstitial nephritis, acute renal failure, oliguria, anuria.

From the nervous system: headache, dizziness, paresthesia, convulsions, encephalopathy, "fluttering" tremor, coma, neuromuscular excitability, myoclonia.

Local reactions: phlebitis, thrombophlebitis, pain along the vein during intravenous administration; morbidity and infiltration at the site of intramuscular injection.

Other: nasal bleeding, candidiasis (candidal vaginitis, oropharyngeal candidiasis), superinfection, false positive Coombs test, increased prothrombin time, false positive urine reaction to glucose, lowering blood pressure.

Overdose:

Symptoms: dizziness, paresthesia, headache, convulsions, abnormalities 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.

Interaction:

Pharmaceutically incompatible aminoglycosides (significant mutual inactivation: the simultaneous use of these drugs should be administered at different sites), vancomycin (precipitate forms depending on the concentration, if necessary, two drugs administered through a tube between their application system for intravenous administration 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% solution of sodium chloride and 5% solution of dextrose; 0.18% sodium chloride solution and 4% dextrose solution; 10% dextrose solution; 10% dextran solution with a molecular weight of 40 thousand.dalton 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 compatible with the solution for intraperitoneal dialysis (lactate).

For intramuscular injection ceftazidime can be diluted with a solution of lidocaine hydrochloride 0.5% or 1% (for adults).

If ceftazidime in a concentration of 4 mg / ml are 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 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.

"Loop" diuretics, aminoglycosides, vancomycin, clindamycin lower ground clearance ceftazidime, thereby increasing the risk of nephrotoxicity. Bacteriostatic antibiotics (incl. chloramphenicol) reduce the effectiveness of the drug. Ceftazidime can disrupt the intestinal microflora, which can lead to a decrease in estrogen reabsorption and a decrease in the effectiveness of combined oral contraceptives.

Special instructions:

Before starting treatment with the drug, you must 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. Simultaneous use of cephalosporins with nephrotoxic drugs, such as aminoglycosides, diuretics (furosemide), may lead to an increased risk of nephrotoxicity.

Because the ceftazidime is excreted by the kidneys, then 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 discontinue the drug, and in more heavy - it is recommended to restore the water-salt and protein balance; appoint metronidazole, bacitracin, or vancomycin. The use of drugs that inhibit

peristalsis of the intestine, contraindicated.

Prolonged use of broad-spectrum antibacterial drugs, including ceftazidime, can lead to an increase in the growth of insensitive microorganisms (for example, Enterococci, Candida), and may require discontinuation of treatment or appropriate therapy. During treatment it is necessary to constantly assess the patient's condition.

As with other beta-lactam antibacterials of a wide spectrum of action, when ceftazidime is used in some initially sensitive strains of microorganisms (for example, Enterobacter spp., Pseudomonas spp, Serratia spp.) can develop resistance. Therefore, in the treatment of infections caused by these microorganisms, periodic studies should be conducted on the sensitivity to antibacterial drugs.

Possible false positive test Coombs and false positive urine reaction to glucose (test Benedict, Feling, Clinintest).

Ceftazidime does not affect the quantitative determination of creatinine by the alkaline-picrate method. During treatment can not be used ethanol because of the possibility of disulfiram-like reactions (sudden "tide" of blood to the face, spastic pain in the abdomen,nausea, vomiting, headache, tachycardia, dyspnea).

Effect on the ability to drive transp. cf. and fur:

Care should be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection, 1 g and 2 g.

Packaging:

By 1.0 g in terms of ceftazidime in a bottle of neutral colorless glass with a capacity of 10 ml closed by a rubber stopper, crimped with an aluminum cap with a protective plastic cover for the first opening.

By 2.0 g in terms of ceftazidime in a bottle of neutral colorless glass with a capacity of 10 ml or 25 ml closed with a rubber stopper, crimped with an aluminum cap with a protective plastic cover of the first opening.

Each label is labeled.

For 1 or 10 vials together with the instruction for use are put in a cardboard pack. 50 bottles, together with an equal number of instructions for use, are placed in a cardboard pack (for hospitals); it is allowed to use plastic pallets for bottles.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002753

Date of registration:11.12.2014

Date of cancellation:2019-12-11

The owner of the registration certificate:VIAL, LLC VIAL, LLC Russia

Manufacturer: & nbsp

VIAL, LLC Russia

Information update date: & nbsp07.11.2015

Illustrated instructions

Instructions

Ceftazidime-Vial (Ceftazidime-Vial)