Abitazim powder for solution for injection 1 g No. 10

Instructions Abitazim powder for solution for injection 1 g No. 10

Composition

active ingredient: ceftazidime;

1 vial contains 1.164 g of ceftazidime pentahydrate, equivalent to 1 g of ceftazidime;

excipient: sodium carbonate anhydrous.

Dosage form

Powder for solution for injection.

Main physicochemical properties: white or pale yellow powder.

Pharmacotherapeutic group

Antibacterials for systemic use. Other beta-lactam antibiotics. Third generation cephalosporins. Ceftazidime. ATX code J01D D02.

Pharmacological properties

Pharmacodynamics.

Ceftazidime is a bactericidal cephalosporin antibiotic that acts by inhibiting bacterial cell wall synthesis. Acquired resistance to the antibiotic varies regionally and may vary over time, and may vary significantly between strains. It is advisable to use local susceptibility data and information on the prevalence of extended-spectrum beta-lactamase-producing organisms, especially in the treatment of severe infections.

Sensitive microorganisms.

Gram-positive aerobes: Streptococcus pyogenes, Streptococcus agalactiae.

Gram-negative aerobes: Citrobacter koseri, Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Proteus mirabilis, Proteus spp., Providencia spp., Pasteurella multocida.

Strains with possible acquired resistance.

Gram-negative aerobes: Acinetobacter baumannii, Burkholderia cepacia, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella spp., Pseudomonas aeruginosa, Serratia spp., Morganella morganii.

Gram-positive aerobes: Staphylococcus aureus, Staphylococcus pneumonia, Viridans group streptococcus.

Gram-positive anaerobes: Clostridium perfringens, Peptococcus spp., Peptosteptococcus spp. Gram-negative anaerobes: Fusobacterium spp.

Insensitive microorganisms.

Gram-positive aerobes: Enterococcus spp., including E. faecalis and E. faecium, Listeria spp. Gram-positive anaerobes: Clostridium difficile.

Gram-negative anaerobes: Bacteroides spp., including B. fragilis.

Others: Chlamydia spp., Mycoplasma spp., Legionella spp.

Pharmacokinetics.

In patients, mean peak concentrations of 18 mg/L and 37 mg/L are rapidly achieved after intramuscular injection of 500 mg and 1 g, respectively. Five minutes after intravenous bolus administration of 500 mg, 1 g or 2 g, mean serum concentrations of 46 mg/L, 87 mg/L or 170 mg/L, respectively, are achieved. Therapeutically effective concentrations remain in the serum even 8–12 hours after intravenous and intramuscular administration. Plasma protein binding is approximately 10%. Ceftazidime concentrations exceeding the MIC for most common pathogens are achieved in tissues and media such as bone, heart, bile, sputum, intraocular, synovial, pleural and peritoneal fluids. Ceftazidime readily crosses the placenta and into breast milk. The drug does not penetrate the intact blood-brain barrier well, and in the absence of inflammation, the concentration in the CNS is low. However, in inflammation of the meninges, the concentration of ceftazidime in the CNS is 4–20 mg/l and higher, which corresponds to the level of its therapeutic concentration.

Ceftazidime is not metabolized in the body. After parenteral administration, high and stable serum concentrations of ceftazidime are achieved. The elimination half-life is approximately 2 hours. The drug is excreted unchanged, in the active form, in the urine by glomerular filtration; approximately 80-90% of the dose is excreted in the urine within 24 hours. In patients with impaired renal function, the elimination of ceftazidime is reduced, so the dose should be reduced. Less than 1% of the drug is excreted in the bile, which significantly limits the amount of drug that reaches the intestine.

Indication

Treatment of the following infections in adults and children, including newborns:

nosocomial pneumonia;

respiratory tract infections in patients with cystic fibrosis;

bacterial meningitis;

chronic otitis media;

malignant external otitis;

complicated urinary tract infections;

complicated skin and soft tissue infections;

complicated abdominal infections;

bone and joint infections;

Dialysis-associated peritonitis in patients on continuous ambulatory peritoneal dialysis.

Treatment of bacteremia occurring in patients as a result of any of the above infections.

Ceftazidime can be used to treat patients with neutropenia and fever resulting from a bacterial infection.

Ceftazidime can be used to prevent urinary tract infections during prostate surgery (transurethral resection).

When prescribing ceftazidime, its antibacterial spectrum, directed mainly against gram-negative aerobes, should be taken into account (see sections “Pharmacological properties” and “Special instructions for use”).

Ceftazidime should be used with other antibacterial agents when it is expected that the range of microorganisms causing the infection is not within the spectrum of activity of ceftazidime. The drug should be prescribed in accordance with existing official guidelines for the use of antibacterial agents.

Contraindication

Hypersensitivity to cephalosporin antibiotics.

History of severe hypersensitivity (e.g. anaphylactic reactions) to other beta-lactam antibiotics (penicillins, monobactams and carbapenems).

Interaction with other medicinal products and other types of interactions

Concomitant use of high doses of ceftazidime with nephrotoxic drugs may adversely affect renal function (see section 4.4). Chloramphenicol is an antagonist of ceftazidime and other cephalosporins in vitro. The clinical significance of this phenomenon is unknown, however, if concomitant use of ceftazidime with chloramphenicol is proposed, the possibility of antagonism should be considered.

Like other antibiotics, Abitazim may affect the intestinal flora, leading to reduced reabsorption of estrogens and reduced effectiveness of combined oral contraceptives.

Ceftazidime does not affect the results of glycosuria determination by enzymatic methods, however, a slight effect on the analysis results may be observed when using copper reduction methods (Benedict, Fehling, Clinitest).

Ceftazidime does not affect the alkaline picrate method of creatinine determination.

Application features

As with other beta-lactam antibiotics, severe and sometimes fatal hypersensitivity reactions have been reported. If severe hypersensitivity reactions occur, ceftazidime treatment should be discontinued immediately and appropriate emergency measures should be initiated.

Before initiating treatment, the patient should be evaluated for a history of severe hypersensitivity reactions to ceftazidime, cephalosporin antibiotics, or other beta-lactam antibiotics. Caution should be exercised when prescribing the drug to patients who have had non-severe hypersensitivity reactions to other beta-lactam antibiotics.

Ceftazidime has a limited spectrum of antibacterial activity. It is not an acceptable agent for monotherapy for some types of infections unless the causative agent is known to be susceptible to ceftazidime or there is a high probability that the causative agent will be susceptible to ceftazidime. This is particularly important when considering the treatment of patients with bacteremia, bacterial meningitis, skin and soft tissue infections, and bone and joint infections. In addition, ceftazidime is susceptible to hydrolysis by some extended-spectrum beta-lactamases. Therefore, information on the distribution of organisms producing extended-spectrum beta-lactamases should be taken into account when choosing ceftazidime for treatment. Concomitant treatment with high doses of cephalosporins and nephrotoxic drugs such as aminoglycosides or potent diuretics (e.g. furosemide) may adversely affect renal function. Clinical experience with ceftazidime has shown that this is unlikely when the recommended dosage is observed. There is no evidence that ceftazidime adversely affects renal function at normal therapeutic doses.

Ceftazidime is excreted by the kidneys, so the dose should be reduced according to the degree of renal impairment. Cases of neurological complications have been reported when the dose was not reduced accordingly (see sections "Method of administration and dosage" and "Adverse reactions").

As with other broad-spectrum antibiotics, prolonged treatment with Abitazyme may result in overgrowth of non-susceptible organisms (e.g. Candida, Enterococci); in such cases, discontinuation of treatment or other appropriate measures may be necessary. It is important to monitor the patient closely. Pseudomembranous colitis has been reported with antibiotics, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who develop diarrhoea during or after antibiotic treatment. In the event of prolonged or severe diarrhoea or if the patient develops abdominal cramps, treatment should be discontinued immediately, the patient should be further evaluated and, if necessary, specific treatment for Clostridium difficile should be initiated. Drugs that slow intestinal motility should not be administered. As with other cephalosporins and broad-spectrum penicillins, some previously susceptible strains of Enterobacter spp. and Serratia spp. may become resistant during treatment with ceftazidime. In such cases, susceptibility testing should be performed periodically. Important information about excipients.

Abitazime contains sodium (1 vial of 1 g of ceftazidime contains 52.44 mg (2.28 mmol) of sodium, which should be taken into account when treating patients on a controlled sodium diet.

Use during pregnancy or breastfeeding

Data on the use of ceftazidime in pregnant women are limited. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic or postnatal development. The drug should be prescribed to pregnant women only if the benefit of its use outweighs the possible risk.

Ceftazidime is excreted in breast milk in small amounts, but at therapeutic doses no effects on the breastfed infant are expected. Ceftazidime can be used during breast-feeding.

Ability to influence reaction speed when driving vehicles or other mechanisms

No relevant studies have been conducted. However, certain adverse reactions (e.g. dizziness) may occur, which may affect the ability to drive or use machines (see section "Adverse reactions").

Method of administration and doses

Table 1

Adults and children weighing ≥ 40 kg

*If associated or suspected to be associated with infections listed in the Indications section.

Table 2

Children < 40 kg

*If associated or suspected to be associated with infections listed in the Indications section.

Children.

The safety and efficacy of Abitazim by continuous intravenous infusion in infants and children ≤ 2 months of age have not been established.

Elderly patients.

Given the reduced clearance of ceftazidime, for elderly patients with acute infections, the daily dose should usually not exceed 3 g, especially for patients over 80 years of age.

Liver failure.

No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. Clinical studies have not been conducted in patients with severe hepatic impairment. Close clinical monitoring of efficacy and safety is recommended.

Ceftazidime is excreted unchanged by the kidneys, so the dose should be reduced in patients with impaired renal function.

The initial loading dose should be 1 g. The maintenance dose should be based on creatinine clearance.

The recommended maintenance doses of ceftazidime in renal failure are intermittent administration.

Table 3

Adults and children weighing ≥ 40 kg body weight

In patients with severe infections, the single dose may be increased by 50% or the frequency of administration may be increased accordingly. In such patients, it is recommended to monitor the serum level of ceftazidime.

In children, creatinine clearance should be adjusted for body surface area or body weight.

Table 4

Children weighing < 40 kg

* Serum creatinine level calculated according to guidelines and may not accurately reflect the degree of renal impairment in all patients with renal insufficiency. ** Creatinine clearance calculated from body surface area or determined.

Careful clinical monitoring of the efficacy and safety of the medicinal product is recommended.

The recommended maintenance dose of ceftazidime in renal failure is a continuous infusion.

Table 5

Adults and children weighing ≥ 40 kg.

Dose selection should be done with caution. Close clinical monitoring of efficacy and safety is recommended.

Children with a body weight < 40 kg.

The safety and efficacy of Abitazim by continuous intravenous infusion in children weighing < 40 kg with renal impairment have not been established. Close clinical monitoring of efficacy and safety is recommended.

If ceftazidime is to be administered by continuous intravenous infusion to children with renal impairment, creatinine clearance should be adjusted according to the child's body surface area or body weight.

Hemodialysis.

The half-life of ceftazidime from serum during hemodialysis is 3 to 5 hours.

After each hemodialysis session, a maintenance dose of ceftazidime should be administered as recommended in Tables 6–7 below.

Peritoneal dialysis.

Ceftazidime can be used in routine peritoneal dialysis and in long-term ambulatory peritoneal dialysis.

In addition to intravenous administration, ceftazidime can be included in the dialysis fluid (usually 125 mg to 250 mg per 2 liters of dialysis solution).

For patients with renal insufficiency undergoing long-term arteriovenous hemodialysis or high-flux hemofiltration in intensive care units, the recommended dose is 1 g per day as a single dose or in divided doses. For low-flux hemofiltration, doses should be used as for renal impairment. For patients undergoing venovenous hemofiltration and venovenous hemodialysis, dosage recommendations are given in Tables 6–7.

Table 6

Ceftazidime dosing recommendations for patients undergoing long-term venovenous hemofiltration.

aThe maintenance dose should be administered every 12 hours.

Table 7

Ceftazidime dosing recommendations for patients undergoing long-term venovenous hemodialysis

aThe maintenance dose should be administered every 12 hours.

Introduction.

Abitazime should be administered by intravenous injection or infusion or by deep intramuscular injection. The recommended sites for intramuscular injection are the upper outer quadrant of the gluteus maximus or the lateral thigh. Ceftazidime solutions may be administered directly into a vein or into an intravenous infusion line if the patient is receiving parenteral fluids.

The dose depends on the severity of the disease, sensitivity, location and type of infection, as well as the patient's age and renal function.

Instructions for preparing the solution.

Abitazime is compatible with most intravenous solutions. However, it should not be used as a diluent for sodium bicarbonate for injection (see section "Incompatibility"). The vials are manufactured under reduced pressure. As the drug dissolves, carbon dioxide is released and the pressure in the vial increases. Small bubbles of carbon dioxide in the dissolved drug can be ignored.

Table 8

Note: Reconstitution for intravenous infusion should be performed in two steps (see text below).

The color of the solution varies from light yellow to amber depending on the concentration, solvent, and storage conditions.

If the recommendations are followed, the effect of the drug does not depend on variations in its color.

Ceftazidime in concentrations from 1 mg/ml to 40 mg/ml is compatible with the following solutions: 0.9% sodium chloride solution; M/6 sodium lactate solution; Hartmann's solution; 5% glucose solution; 0.225% sodium chloride solution and 5% glucose solution; 0.45% sodium chloride solution and 5% glucose solution; 0.9% sodium chloride solution and 5% glucose solution; 0.18% sodium chloride solution and 4% glucose solution; 10% glucose solution; 10% glucose solution 40 and 0.9% sodium chloride solution; 10% glucose solution 40 and 5% glucose solution; 6% dextran 70 solution and 0.9% sodium chloride solution; 6% dextran 70 solution and 5% glucose solution.

Ceftazidime in concentrations from 0.05 mg/ml to 0.25 mg/ml is compatible with intraperitoneal dialysis fluid (lactate).

Ceftazidime for intramuscular administration can be dissolved in 0.5% or 1% lidocaine hydrochloride solution.

The effectiveness of the drug is maintained when ceftazidime 4 mg/ml is mixed with the following substances: hydrocortisone (hydrocortisone sodium phosphate) 1 mg/ml in 0.9% sodium chloride solution for injection or 0.5% glucose solution; cefuroxime (cefuroxime sodium) 3 mg/ml in 0.9% sodium chloride solution for injection; cloxacillin (cloxacillin sodium) 4 mg/ml in 0.9% sodium chloride solution for injection; heparin 10 IU/ml or 50 IU/ml in 0.9% sodium chloride solution for injection; potassium chloride 10 mEq/l or 40 mEq/l in 0.9% sodium chloride solution for injection.

The contents of the Abitazim 1 g vial, dissolved in 3 ml of water for injection, can be added in an amount of 1.5 ml to a solution of metronidazole (500 mg in 100 ml), while both drugs retain their activity.

Preparation of solutions for intramuscular or intravenous bolus injection:

1. Insert the syringe needle through the vial cap and inject the recommended volume of solvent.

2. Remove the syringe needle and shake the vial until a clear solution is obtained.

3. Turn the vial upside down. With the syringe plunger fully inserted, insert the needle into the vial. Draw all the solution into the syringe, keeping the needle in the solution at all times. Small bubbles of carbon dioxide can be ignored.

Preparation of solutions for intravenous infusion (1 g vial) in 2 stages:

1. Insert the syringe needle through the vial cap and inject 10 ml of solvent.

2. Remove the syringe needle and shake the vial until a clear solution is obtained.

3. Do not insert the air needle until the medicine is completely dissolved. Insert the air needle through the cap into the vial to relieve the internal pressure in the vial.

4. Add the resulting solution to the intravenous infusion system, creating a total solution volume of at least 50 ml and use for intravenous infusion for 15–30 minutes.

Note: To ensure the sterility of the medication, it is very important not to insert the air needle through the cap until the medication is completely dissolved.

The prepared solution can be stored for 24 hours at a temperature not exceeding 25 °C or for 7 days at a temperature of 4 °C.

Children.

Apply to children from the first days of life.

Overdose

Symptoms: Overdose may lead to neurological complications such as encephalopathy, convulsions and coma. Symptoms of overdose may occur in patients with renal insufficiency unless the dose is reduced accordingly (see sections 4.4 and 4.2).

Treatment: Serum ceftazidime concentrations can be reduced by hemodialysis or peritoneal dialysis.

Side effects

Adverse reactions were classified according to their frequency of occurrence - from very common to uncommon, as well as by organ system: very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1000 and <1/100); rare (≥1/10000 and <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data).

Infections and infestations:

Uncommon: candidiasis (including vaginitis and candidal stomatitis).

Blood and lymphatic system disorders:

Often - eosinophilia and thrombocytosis.

Uncommon: leukopenia, neutropenia and thrombocytopenia.

Frequency unknown - lymphocytosis, hemolytic anemia and agranulocytosis.

On the part of the immune system:

Frequency unknown - anaphylaxis (including bronchospasm and/or hypotension). Nervous system disorders:

Uncommon: dizziness, headache.

Frequency unknown – paresthesia.

Cases of neurological complications, such as tremor, myoclonus, seizures, encephalopathy and coma, have been reported in patients with renal insufficiency in whom the dose of ceftazidime was not reduced accordingly.

From the cardiovascular system:

Often - phlebitis or thrombophlebitis at the site of drug injection.

From the gastrointestinal tract:

Often - diarrhea.

Uncommon: nausea, vomiting, abdominal pain and colitis.

As with other cephalosporins, colitis may be associated with Clostridium difficile and may present as pseudomembranous colitis (see section 4.4).

Frequency unknown – taste disturbance.

From the kidneys and urinary system:

Uncommon: transient increase in blood urea.

Very rare - interstitial nephritis, acute renal failure.

From the liver and biliary tract:

Often - transient increase in the level of one or more liver enzymes (ALT, AST, LDH, GGT, alkaline phosphatase).

Frequency unknown – jaundice.

Skin and subcutaneous tissue disorders:

Often – maculopapular rashes or urticaria.

Uncommon: itching.

Frequency unknown - angioedema, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.

General disorders and administration site conditions:

Common: Pain and/or inflammation at the site of intramuscular injection.

Uncommon: fever.

Laboratory indicators:

Often a positive Coombs test.

Uncommon - As with some other cephalosporins, transient increases in blood urea, blood urea nitrogen and/or serum creatinine have occasionally been observed. A positive Coombs test has been observed in approximately 5% of patients, which may affect blood typing.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Expiration date

3 years.

The prepared solution can be stored for 24 hours at a temperature not exceeding 25 °C or for 7 days at a temperature of 4 °C.

Storage conditions

Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Incompatibility

Abitazime is less stable in sodium bicarbonate solution for injection than in other intravenous solutions, therefore sodium bicarbonate solution for injection is not recommended as a diluent.

Ceftazidime and aminoglycosides should not be mixed in the same infusion line or syringe. Precipitation has been observed when vancomycin has been added to ceftazidime solutions. Therefore, it is recommended that infusion lines and intravenous catheters be flushed between the administration of these two drugs.

Packaging

1 g of powder in a vial, 1 or 10 vials in a cardboard box.

Vacation category

According to the recipe.

Producer

ACS DOBFAR S.P.A.

Location of the manufacturer and address of its place of business.

INDUSTRIAL NUCLEUS OF S. ATTO (LOC. OF S. NICOLO' A TORDINO),

64100 TERAMO (TE), Italy

or

VIA ALESSANDRO FLEMING, 2, VERONA (VR), 37135, Italy.