Denizide powder for solution for injection 1 g vial No. 1

Instructions Denizide powder for solution for injection 1 g bottle No. 1

Composition

active ingredient: ceftazidime;

1 vial contains ceftazidime pentahydrate (as a sterile mixture with anhydrous sodium carbonate), equivalent to 1 g of ceftazidime;

excipients: sodium carbonate anhydrous.

Dosage form

Powder for solution for injection.

Main physicochemical properties: white to cream-colored crystalline 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 whose mechanism of action is associated with disruption of bacterial cell wall synthesis.

Acquired antibiotic resistance varies between regions and can change over time, and can vary significantly within individual strains. It is advisable to use local antibiotic susceptibility data, especially when treating severe infections.

Sensitive microorganisms

Gram-positive aerobes: Streptococcus pyogenes, Streptococcus agalactiae.

Gram-negative aerobes: Citrobacter koseri, Escherichia coli, Haemophilus influenza, Moraxella catarrhalis, Neisseria meningitides, Proteus mirabilis, Proteus spp., Providencia spp..

Strains that may acquire resistance

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

Gram-positive aerobes: Staphylococcus aureus, Staphylococcus pneumonia.

Gram-positive anaerobes: Clostridium perfringens, Peptococcus spp., Peptostreptococcus spp.,

Gram-negative anaerobes: Fusobacterium spp.

Non-susceptible 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, after intramuscular injection of 1 g of the drug, mean peak concentrations of 37 mg/l are rapidly reached. After 5 minutes after intravenous bolus administration of 1 g or 2 g, serum concentrations of 87 or 170 mg/l, respectively, are reached. 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 minimum inhibitory concentration for most common pathogens are achieved in tissues and media such as bone, heart, bile, sputum, intraocular, synovial, pleural and peritoneal fluids. Ceftazidime rapidly crosses the placenta and into breast milk. The drug penetrates poorly through the intact blood-brain barrier, and in the absence of inflammation, the concentration of the drug in the central nervous system 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 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 the 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 otitis externa; 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.

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

Ceftazidime can be used to prevent infectious complications during prostate surgery (transurethral resection).

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

Ceftazidime should be used with other antibacterial agents if it is expected that some of the microorganisms causing the infection are not within the spectrum of activity of ceftazidime.

The drug should be prescribed in accordance with current official recommendations for the prescription of antibacterial agents.

Contraindication

Hypersensitivity to ceftazidime or to any of the excipients. 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 the drug with nephrotoxic drugs may adversely affect renal function (see section "Special warnings and precautions for use").

Chloramphenicol is an antagonist of ceftazidime and other cephalosporins in vitro. The clinical significance of this phenomenon is unknown, but if concomitant use of Denizide with chloramphenicol is necessary, the possibility of antagonism should be considered.

Like other antibiotics, Denizide 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, treatment with ceftazidime should be discontinued immediately and appropriate emergency measures should be taken.

Before initiating treatment, the patient should be evaluated for a history of severe hypersensitivity reactions to ceftazidime, cephalosporin antibiotics, or other beta-lactam antibiotics. The drug should be administered with caution to patients who have had non-serious hypersensitivity reactions to other beta-lactam antibiotics.

Ceftazidime has a limited spectrum of antibacterial activity. It is not an acceptable drug for monotherapy for some types of infections, except in cases where the causative agent of the disease is unknown or there is a high probability that the possible causative agent will be susceptible to treatment with ceftazidime. This is especially 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, when choosing ceftazidime for treatment, information on the distribution of microorganisms that produce extended-spectrum beta-lactamases should be taken into account.

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 phenomenon is unlikely when the recommended dosage is observed. There is no evidence that ceftazidime adversely affects renal function at usual 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 Denizide may result in overgrowth of non-susceptible organisms (e.g. Candida, Enterococci); in this case, discontinuation of treatment or other appropriate measures may be necessary. It is very important to constantly monitor the patient's condition.

Pseudomembranous colitis, ranging in severity from mild to life-threatening, has been reported in association with antibiotics. Therefore, it is important to consider the possibility of this diagnosis in patients who develop diarrhoea during or after antibiotic treatment. In the event of prolonged and 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. Medicinal products that slow intestinal motility should not be administered.

As with other cephalosporins and broad-spectrum penicillins, some susceptible strains of Enterobacter spp. and Serratia spp. may become resistant during treatment with ceftazidime. In such cases, periodic susceptibility testing should be performed.

The drug contains sodium (a vial with 1 g of ceftazidime contains 52 mg of sodium), which should be taken into account when treating patients who are on a sodium-controlled diet.

Ability to influence reaction speed when driving vehicles or other mechanisms

No relevant studies have been conducted. However, the occurrence of adverse reactions such as dizziness may affect the ability to drive or use machines (see section "Adverse reactions").

Use during pregnancy or breastfeeding

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.

Method of administration and doses

Adults and children ≥ 40 kg

Children < 40 kg

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

Children.

The safety and efficacy of Denizide 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.

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.

Kidney failure.

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

The initial dose should be 1 g. The maintenance dose should be based on the glomerular filtration rate.

Recommended maintenance doses of ceftazidime in renal failure: intermittent administration.

Adults and children weighing ≥ 40 kg

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.

Children < 40 kg

*This is a serum creatinine level calculated according to guidelines, which may not accurately reflect the level of renal function decline in patients with renal failure.

** Creatinine clearance calculated based on body surface area or determined.

Close clinical monitoring of efficacy and safety is recommended.

Recommended maintenance doses of ceftazidime in renal failure: continuous infusion

Adults and children weighing ≥ 40 kg

The dose should be carefully selected. Close clinical monitoring of efficacy and safety is recommended.

Children < 40 kg

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

If children with impaired renal function need to be administered the drug by continuous intravenous infusion, 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 the table 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 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 in a single dose or in divided doses. For low-flux hemofiltration, doses should be used as for impaired renal function.

For patients undergoing venovenous hemofiltration and venovenous hemodialysis, dosage recommendations are provided in the tables.

Ceftazidime dosing recommendations for patients undergoing long-term venovenous hemofiltration

aThe maintenance dose should be administered every 12 hours.

Ceftazidime dosing recommendations for patients undergoing long-term venovenous hemodialysis

aThe maintenance dose should be administered every 12 hours.

Introduction.

Denizide should be administered by intravenous injection or infusion, or by deep intramuscular injection. The recommended sites for intramuscular administration are the upper outer quadrant of the gluteus maximus muscle or the lateral part of the thigh.

Ceftazidime solutions can be administered directly into a vein or into an intravenous infusion system if the patient is receiving fluids parenterally.

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.

Acquired antibiotic resistance varies between regions and can change over time, and can vary significantly within individual strains. It is advisable to use local antibiotic susceptibility data, especially when treating severe infections.

Preparation of the solution.

Denizide is compatible with most commonly used intravenous solutions. However, sodium bicarbonate for injection should not be used as a solvent (see "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.

* Dissolution should be carried out in two stages (see 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.

When using lidocaine solution as a solvent for intramuscular administration of the drug, it is necessary to take into account information on the safety of lidocaine.

The effectiveness of both drugs 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 a 1 g bottle of Denizide, dissolved in 1.5 ml of water for injection, can be added 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

Insert the syringe needle through the vial cap and inject the recommended volume of solvent. Remove the syringe needle and shake the vial until a clear solution is obtained. Invert the vial. With the syringe plunger fully depressed, insert the needle into the vial. Draw up all of 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 vials)

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

The prepared solution can be stored for no more than 8 hours at a temperature not exceeding 25 °C and no more than 24 hours at a temperature from 2 to 8 °C.

Children

It is used for children from the first days of life.

Overdose

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 4.2 and 4.4). Serum ceftazidime concentrations can be reduced by haemodialysis or peritoneal dialysis.

Adverse reactions

Adverse reactions were classified by organ system and frequency of occurrence: 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.

Infections and infestations

Uncommon: candidiasis (including vaginitis and aphthous stomatitis).

Circulatory and lymphatic systems.

Often - eosinophilia and thrombocytosis.

Uncommon: leukopenia, neutropenia and thrombocytopenia.

Frequency unknown - lymphocytosis, hemolytic anemia and agranulocytosis.

Immune system

Frequency unknown - anaphylaxis (including bronchospasm and/or hypotension).

Nervous system

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.

Vascular disorders

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

Gastrointestinal disorders

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.

Urinary system

Very rare - interstitial nephritis, acute renal failure.

Hepatobiliary reactions

Often - transient increase in the level of one or more liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase).

Frequency unknown – jaundice.

Skin and subcutaneous tissue

Often – maculopapular rash 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: Transient increase in blood urea, blood urea nitrogen and/or serum creatinine.

A positive Coombs test is observed in approximately 5% of patients, which may affect blood typing.

Expiration date

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

1 bottle in a cardboard box.

Vacation category

According to the recipe.

Producer

Swiss Parenterals Ltd./ Swiss Parenterals Ltd.

Location of the manufacturer and its business address

Unit II, Plot No. 402, 412-414 Kerala Industrial Estate, GIDC, Near Bavla, Ahmedabad, Gujarat, 382220, India.