Ceftazidime-Akos, 1 g

The drug Ceftazidime is an antibacterial drug of III generation cephalosporins group, it has a broad spectrum and acts bactericidally, disrupts cell wall synthesis of microorganisms, resistant to the action of most beta-lactamases. The drug is active against Gram-negative microorganisms: Haemophilus influenzae, Neisseria gonorrhoeae and other Neisseria spp. and most representatives of the family Enterobacteriaceae (Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella pneumoniae and other Klebsiella spp, Morganella morganii and other Morganella spp., Proteus mirabilis (including indole-positive), Proteus vulgaris and other Proteus spp., Providena rettgeri and other Providena spp. and Serratia spp.), Acinetobacter spp., Haemophilus parainfluenzae (including ampicillin-resistant strains), Pasteurella multocida. Salmonella spp., Shigella spp. and Yersinia enterocolitica.

The drug ceftazidime has the highest activity among III generation cephalosporins against Pseudomonas aeruginosa and intrahospital infection. The drug is active against Gram-positive bacteria: Micrococcus spp., Streptococcus aureus, Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pyogenes group A, Streptococcus viridans and other Streptococcus spp. (excluding Streptococcus faecalis); strains sensitive to methicillin: Staphylococcus aureus, Staphylococcus epidermidis.

The drug Ceftazidime is active against anaerobic bacteria: Bacteroides spp. (most strains of Bacteroides fragilis are resistant), Clostridium perfringens, Peptococcus spp., Peplostreptococcus spp. and Propionobacterium spp. The drug is not active against methicillin-resistant strains of Campilobacter spp., Chlamydia spp., Clostridium difficile, Enterococcus spp., Listeria monocytogenes and other Lisleria spp., Staphylococcus aureus and Staphylococcus epidermidis; Streptococcus faecalis.

Pharmacokinetics

After administration, the drug is rapidly distributed in the human body and reaches therapeutic concentrations in most tissues and fluids, including synovial, pericardial and peritoneal fluid as well as in bile, sputum and urine. Distribution also occurs in bones, myocardium, gallbladder, skin and soft tissues at concentrations sufficient to treat infectious diseases, especially in inflammatory processes that increase diffusion of the drug. It penetrates poorly through the intact blood-brain barrier, but the therapeutic level reached by the drug in the cerebrospinal fluid is sufficient to treat meningitis.

It binds irreversibly with plasma proteins (less than 15%), and has bactericidal effect only in free form. The degree of binding to proteins does not depend on the concentration. Maximal concentration after intramuscular introduction of 0.5 g or 1 g is 17 mkg/ml and 39 mkg/ml, when administered intravenously it is 42 mkg/ml and 69 mkg/ml, respectively. Time of reaching maximum concentration when administered intramuscularly is 1 h, when administered intravenously – by the end of the infusion. The drug concentration equal to 4 µg/ml is maintained for 6-8 hours. Therapeutic concentration in plasma is maintained for 8-12 hours.

Half-life in normal renal function is 1.8 hours; in impaired renal function 2.2 hours. The drug is not metabolized in the liver, hepatic dysfunction does not affect the pharmacodynamics and pharmacokinetics of the drug. The dose in such patients remains normal. It is excreted unchanged by the kidneys up to 80-90% (70% of the administered dose is excreted in the first 4 hours) during 24 hours by glomerular filtration and tubular secretion to an equal extent.

In case of impaired renal function it is recommended to reduce the dose. The volume of distribution is 0.21-0.28 l/kg. The drug accumulates in the soft tissues, kidneys, lungs, bones and joints, serous cavities.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

Active ingredient

Composition

1 vial of powder for preparation of solution for injection contains:

the active ingredient:

1.0 g ceftazidime pentahydrate sodium carbonate (in terms of ceftazidime)

How to take, the dosage

The drug Ceftazidime-ACOS is used only parenterally: intravenously (by stream or drop) or intramuscularly. The dose of the drug is set individually, taking into account the severity of the disease, localization of infection, type and sensitivity of the pathogen, age and renal function.

The drug is administered intravenously (by stream or drop) or deeply intramuscularly in the area of the upper outer quadrant of the greater gluteal muscle or in the area of the lateral thigh. Ceftazidime solution can be injected directly into a vein or into a tube of an infusion system.

The usual dose for adults and children over 12 years of age is 1 g intramuscularly or intravenously every 8-12 hours.

In uncomplicated urinary tract infections, 250 mg intramuscularly or intravenously every 12 hours.

In complicated urinary tract infections, 0.5-1 g intravenously every 8-12 hours.

In case of uncomplicated pneumonia, skin and soft tissue infections – intramuscularly or intravenously 0.5-1 g every 8 hours.

In cystic fibrosis, respiratory tract infections caused by Pseudomonas spp. – intravenously at a dose of 100-150 mg/kg/day, the frequency of administration is 3 times/day (using a dose of up to 9 g/day in these patients has not caused complications).

In case of infections of bones and joints – intravenously 2 g every 12 hours.

In severe infections, including nosocomial infections – intravenously 2 g every 8 hours.

In extremely severe or life-threatening infections – intravenously 2 g every 8 hours.

In elderly patients, the maximum daily dose should not exceed 3 g.

Patients with renal insufficiency require dose reduction because ceftazidime is excreted unchanged by the kidneys. The initial dose is 1 g. The maintenance dose is adjusted depending on the glomerular filtration rate.

Creatinine clearanceDose>50 ml/min (>0.83 ml/sec)Usual dose for adults and children over 12 years old35-50 ml/min
(0.52-0.52-0.83 ml/sec)1 g every 12 hours16-30 ml/min
(0.27-0.5 ml/sec)1 g every 24 hours6-15 ml/min
(0.1-0.25 ml/sec)500 mg every 24 hours<5 ml/min (<0.08 ml/sec)500 mg every 48 hoursPatients on hemodialysis1 g after each session of hemodialysisPatients on peritoneal dialysis500 mg every 24 hours

Patients with severe infections may increase the maintenance dose by 50% or increase the frequency of administration. In this case, serum ceftazidime levels should be monitored; serum ceftazidime concentration should not exceed 40 mg/l.

In children, creatinine clearance is calculated according to ideal weight or body surface area.

The T1/2 of the drug during hemodialysis is 3-5 hours. The appropriate dose of the drug should be repeated after each period of dialysis.

In peritoneal dialysis, ceftazidime can be included in the dialysis solution at a dose of 125 mg to 250 mg per 2 L of dialysis solution.

In patients with renal failure who are on continuous hemodialysis using an arteriovenous shunt and in patients on high rate hemofiltration in the intensive care unit, the recommended doses are 1 g/day daily (in 1 or more administrations).

In patients on low-rate hemofiltration, doses recommended for impaired renal function are administered.

In children under 2 months of age, 25-60 mg/kg/day (in 2 injections) is prescribed.

Children from 2 months to 12 years of age are prescribed 30-100 mg/kg/day (in 2-3 injections).

In children with reduced immunity, cystic fibrosis and meningitis, 150 mg/kg/day (in 3 injections).

The maximum daily dose of ceftazidime for children is 6 g.

The duration of treatment

The duration of treatment with ceftazidime is 7-14 days. In infections caused by Pseudomonas aeruginosa (pneumonia, cystic fibrosis, meningitis) the course of treatment may be increased up to 21 days.

Regulations for preparing solutions

Carbon dioxide (carbon dioxide) is released when the powder is dissolved. After the solvent is injected, the bottle should be shaken to produce a clear solution. In the resulting ready solution of the drug there may be small bubbles of carbon dioxide (carbon dioxide).

The resulting solution may be light yellow to dark yellow. If all of the recommended dilution rules are followed, the effectiveness of the product is not affected by the color.

Primary dilution

Dose
volume
of propellant
for intramuscular administration
volume
of propellant
for intravenous administration500 mg1.5 ml water for injection
or 0.5% or 1% lidocaine hydrochloride solution5 ml
water for injection1 g or 2 g3 ml water for injection
or 0.5% or 1% lidocaine hydrochloride solution10 ml
water for injection

Secondary dilution

For intravenous drip administration the solution of Ceftazidime-ACOS obtained in the above described way is additionally diluted in 50-100 ml of one of the following solvents intended for intravenous administration (09% sodium chloride solution, Ringer’s solution, 5% or 10% dextrose (glucose) solution, 5% dextrose (glucose) solution with 0.9% sodium chloride solution. For secondary dilution, only freshly prepared solution should be used.

Interaction

Pharmaceutically incompatible with aminoglycosides, heparin, vancomycin. Sodium bicarbonate solution should not be used as a solvent. Loop diuretics, aminoglycosides, vancomycin, clindamycin reduce the clearance of ceftazidime, resulting in an increased risk of nephrotoxic effects.

Pharmaceutically compatible with the following solutions: 1 to 40 mg/ml sodium chloride 0.9%, sodium lactate, Hartmann’s solution, dextrose 5%, sodium chloride 0.225% and dextrose 5%, sodium chloride 0.45% and dextrose 5%, sodium chloride 0.9% and dextrose 5%, sodium chloride 0.18% and dextrose 4%, dextrose 10%, dextran 40:10% in sodium chloride 0.9% solution, dextran 40:10% in dextrose 5% solution, dextran 70:6% in sodium chloride 0.9% solution, dextran 70:6% in dextrose 5% solution. At concentrations of 0.05 to 0.25 mg/ml ceftazim is compatible with intraperitoneal dialysis solution (lactate).

For intravenous administration, ceftazidime may be diluted with 0.5% or 1% lidocaine hydrochloride solution. Both components retain their activity if ceftazidime is added to the following solutions (ceftazidime concentration 4 mg/ml): hydrocortisone (hydrocortisone sodium phosphate) 1 mg/ml in 0.9% sodium chloride solution or 5% dextrose solution, cefuroxime (cefuroxime sodium) 3 mg/ml in 0.9% sodium chloride solution, cloxacillin (sodium cloxacillin) 4 mg/ml in 0.9% sodium chloride solution, heparin 10 IU/ml or 50 IU/ml in 0.9% sodium chloride solution, potassium chloride 10 mEq/L or 40 mEq/L in 0.9% sodium chloride solution. When mixing a solution of ceftazidime (500 mg in 1.5 ml of water for injection) and metronidazole (500 mg/100 ml) both components retain their activity.

Special Instructions

Patients with a history of allergic reactions to penicillins may have hypersensitivity to cephalosporin antibiotics.

Patients with a history of allergic reactions to penicillin may be hypersensitive to cephalosporin antibiotics.

When using the drug and 2-3 weeks after discontinuation of treatment, development of diarrhea caused by Clostridium difficile is possible.

In mild cases withdrawal of treatment and use of ion exchange resins (colestyramine, colestipol) is sufficient, in severe cases compensation of loss of fluid, electrolytes and protein, prescription of vancomycin, bacitracin or metronidazole is indicated. Do not use drugs that inhibit intestinal peristalsis.

Impact on driving and operating machinery

When undergoing treatment, caution should be exercised while driving motor transport and engaging in other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions because of the risk of dizziness.

Contraindications

With caution: renal failure, history of colitis, malabsorption syndrome (increased risk of decreased prothrombin activity, especially in persons with severe renal and/or hepatic failure), simultaneous administration with a “loop” diuretic and aminoglycoside, and in newborns.

Side effects

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

Digestive system disorders: nausea, vomiting, diarrhea, flatulence, abdominal pain, dysbacteriosis, increased liver transaminase activity, alkaline phosphatase, hyperbilirubinemia, stomatitis, glossitis, pseudomembranous enterocolitis, oropharyngeal candidiasis, cholestasis.

Hematopoietic system disorders: eosinophilia, leukopenia, neutropenia, agranulocytosis, granulocytopenia, thrombocytopenia, hemolytic anemia, lymphocytosis, hemorrhages.

Perior genital system disorders: candidal vaginitis.

Urinary system disorders: renal dysfunction, toxic nephropathy.

CNS disorders: headache, dizziness, paresthesias, dizziness, seizures, encephalopathy, “fluttering tremor”.

Laboratory parameters: hypercreatininemia, increased concentration of urea, false positive urine glucose reaction, false positive direct Coombs reaction, increased prothrombin time.

Local reactions: when administered intravenously – phlebitis; when administered intramuscularly – pain, burning, thickening at the injection site.

Other: nasal bleeding, superinfection.

Overdose

Symptoms: pain, inflammation, phlebitis at the injection site, dizziness, paresthesias, headache, seizures in patients with renal failure, hypercreatininemia, hyperbilirubinemia, thrombocytosis, thrombocytopenia, eosinophilia, leukopenia, prolonged prothrombin time.

Treatment: symptomatic therapy; in case of renal failure – peritoneal dialysis or hemodialysis.

Pregnancy use

In pregnancy, the drug is used only if the estimated benefit to the mother exceeds the potential risk to the fetus and child. If the drug is used during lactation, breastfeeding should be discontinued.

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