Ceftazidime-Vial (Powder) Instructions for Use

Marketing Authorization Holder

Vial, LLC (Russia)

Manufactured By

NCPC Hebei Huamin Pharmaceutical, Co. Ltd. (China)

ATC Code

J01DD02 (Ceftazidime)

Active Substance

Ceftazidime (Rec.INN registered by WHO)

Dosage Form

Ceftazidime-Vial

Powder for solution for intravenous and intramuscular administration 1 g: vial 1 or 10 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous and intramuscular administration white or white with a yellowish tint.

Excipients: anhydrous sodium carbonate – 0.118 g.

1 g – glass vials (1) – cardboard packs.
1 g – glass vials (10) – cardboard packs.
1 g – glass vials (50) – cardboard packs (for hospitals).

Clinical-Pharmacological Group

Third generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Ceftazidime is a third-generation cephalosporin antibiotic for parenteral use. It acts bactericidally (disrupts the synthesis of the microbial cell wall). It has a broad spectrum of action. It is resistant to the action of most beta-lactamases. It acts on many strains resistant to ampicillin and other cephalosporins. In vitro, synergism of ceftazidime and aminoglycosides against some strains of microorganisms is observed, as well as an additive effect.

The prevalence of acquired bacterial resistance to ceftazidime varies by region and over time, and for certain types of microorganisms, resistance can be very high. It is preferable to have local susceptibility data, especially when treating severe infections.

The drug is active in vitro against the following microorganisms.

Bacteria usually susceptible to ceftazidime.

• Gram-negative aerobes: Haemophilus influenzae¹, Haemophilus parainfluenzae, Neisseria meningitidis¹, 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 for which acquired resistance is likely to develop.

• Gram-negative aerobes: Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli¹, Klebsiella spp. (including Klebsiella pneumoniae¹), Pseudomonas spp., (including Pseudomonas aeruginosa¹), Serratia spp.¹, Morganella morganii, Yersinia enterocolitica.
• Gram-positive aerobes: Staphylococcus spp. (including Staphylococcus aureus¹), Streptococcus pneumoniae¹. Streptococcus spp. of the viridans group.
• Gram-positive anaerobes: Clostridium spp. (not including Clostridium difficile), Peptostreptococcus spp., Propionibacterium spp.
• Gram-negative anaerobes: Fusobacterium spp.

Bacteria with 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 Bacteroides fragilis.
• Others: Chlamydia spp., Mycoplasma spp., Legionella spp.

¹– clinical efficacy has been demonstrated for these microorganisms.

Pharmacokinetics

The maximum concentration (C_max) of ceftazidime after intramuscular administration of 0.5 g or 1 g is reached quickly and is 18 µg/ml and 37 µg/ml, respectively. Five minutes after intravenous bolus administration of the drug at a dose of 0.5 g, 1 g or 2 g, C_max is 46 µg/ml, 87 µg/ml and 170 µg/ml, respectively. The therapeutic concentration in blood plasma persists for 8-12 hours after intravenous or intramuscular administration.

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 fluids, as well as in bile, sputum and urine. Distribution also occurs in bones, myocardium, gallbladder, skin and soft tissues.

It penetrates poorly through the intact blood-brain barrier, but in meningitis, the therapeutic concentration achieved by the drug in the cerebrospinal fluid is 4-20 mg/l. It easily crosses the placenta and is excreted in breast milk. Plasma protein binding is less than 10%.

The drug is not metabolized in the liver; impaired liver function does not affect the pharmacokinetics of the drug.

The half-life with normal renal function is about 2 hours; in newborns it is 3-4 times longer; during hemodialysis it is 3-5 hours.

It is excreted unchanged by the kidneys up to 80-90% within 24 hours by glomerular filtration; with bile – less than 1%.

In case of impaired renal function, a dose reduction is recommended.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to ceftazidime.

• Severe infections: peritonitis, septicemia, infections in patients with immunodeficiency, infected burns, severe purulent-septic conditions, meningitis;
• Infections of the lower respiratory tract: pneumonia, lung abscess, pleural empyema, infected bronchiectasis (including in patients with cystic fibrosis);
• Infections of the ENT organs: otitis media, mastoiditis, sinusitis;
• Infections of the urinary tract: 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 during prostate surgery.

ICD codes

Dosage Regimen

The drug is administered intravenously or intramuscularly. The dose of the drug is set individually, taking into account the severity of the disease, the location of the infection and the sensitivity of the pathogen, age and body weight, and renal function.

Adults and children over 12 years old are prescribed 1 g every 8-12 hours or 2 g at 12-hour intervals. For severe infections, especially in patients with reduced immunity (including patients with neutropenia) – 2 g every 8 hours or 3 g every 12 hours. For uncomplicated urinary tract infections – 0.25 g 2 times a day. For complicated urinary tract infections – 0.5-1 g 2 times a day.

For cystic fibrosis, patients with respiratory system infections caused by Pseudomonas spp. – 30-50 mg/kg 3 times a day (maximum dose 9 g/day).

For prostate surgery for prophylactic purposes, 1 g is administered before induction of anesthesia, and the administration is repeated after catheter removal.

Children over 2 months and up to 12 years old are prescribed 30-100 mg/kg/day (in 2-3 administrations), maximum dose – 6 g/day; children with reduced immunity, cystic fibrosis and meningitis – 150 mg/kg/day in 3 administrations, maximum daily dose – 6 g. Newborns and infants under 2 months of age are prescribed 25-60 mg/kg/day in 2 administrations.

Elderly patients – taking into account the possible decrease in creatinine clearance, the recommended dose of ceftazidime should not exceed 3 g/day, especially in patients over 80 years of age.

In case of impaired renal function, the initial dose is 1 g. The maintenance dose is selected depending on the creatinine clearance values as indicated below.

* maintenance dose is administered every 12 hours

The duration of treatment with ceftazidime is 7-14 days. For infections caused by Pseudomonas aeruginosa (pneumonia, infectious complications in cystic fibrosis, meningitis), the course of treatment can be extended to 21 days.

Preparation of solutions

1. “Primary” dilution

2. “Secondary” dilution

For intravenous drip administration, the solution of the drug obtained by the method described above is additionally diluted in 50-100 ml of one of the following solvents intended for intravenous administration.

• 0.9% sodium chloride solution,
• Hartmann’s solution,
• 5% and 10% dextrose solution,
• 5% dextrose solution with 0.9% sodium chloride solution.

Use only a freshly prepared solution!

Adverse Reactions

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, dysbacteriosis, impaired liver function (transient increase in the activity of “hepatic” transaminases, alkaline phosphatase, hyperbilirubinemia), pseudomembranous colitis, jaundice, cholestasis, unpleasant taste in the mouth.

From the hematopoietic organs leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, hemolytic anemia, lymphocytosis, hypocoagulation, pancytopenia, aplastic anemia.

From the urinary system impaired renal function (azotemia, hypercreatininemia, increased blood urea content), toxic nephropathy, interstitial nephritis, acute renal failure, oliguria, anuria.

From the nervous system headache, dizziness, paresthesia, convulsions, encephalopathy, “flapping” tremor, coma, neuromuscular excitability, myoclonus.

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

Others nosebleeds, candidiasis (candidal vaginitis, oropharyngeal candidiasis), superinfection, false-positive direct Coombs test, increased prothrombin time, false-positive urine glucose reaction, decreased blood pressure.

Contraindications

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

With caution

• Impaired renal function;
• Neonatal period;
• History of bleeding;
• History of colitis;
• Malabsorption syndrome (increased risk of decreased prothrombin activity, especially in patients with severe renal and/or hepatic insufficiency);
• Combination with loop diuretics, aminoglycosides.

Use in Pregnancy and Lactation

Use during pregnancy is only possible in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to use the drug during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Renal Impairment

In case of impaired renal function, the initial dose is 1 g. The maintenance dose is selected depending on the creatinine clearance values as indicated below.

Pediatric Use

Children are prescribed according to indications in accordance with the dosage regimen. Use with caution in newborns.

Geriatric Use

For elderly patients – considering the possible decrease in creatinine clearance, the recommended dose of ceftazidime should not exceed 3 g/day, especially in patients over 80 years of age.

Special Precautions

Before starting treatment with the drug, it is necessary to collect a detailed history regarding previous hypersensitivity reactions to Ceftazidime, cephalosporins, penicillins, and other drugs.

In 3-7% of patients with a history of allergy to penicillins, cross-hypersensitivity to cephalosporins has been noted.

If allergic reactions to ceftazidime occur, the drug should be discontinued immediately; in severe cases, the use of epinephrine, glucocorticosteroid hormones, antihistamines, or other emergency measures may be required.

Concomitant use of cephalosporins with nephrotoxic drugs, such as aminoglycosides, diuretics (furosemide), may lead to an increased risk of nephrotoxic effects.

Since Ceftazidime is excreted by the kidneys, its dose should be reduced in patients with impaired renal function according to the degree of impairment.

Ceftazidime may interfere with vitamin K synthesis due to suppression of intestinal flora, which can cause a decrease in the levels of vitamin K-dependent blood clotting factors, and in rare cases lead to hypoprothrombinemia and bleeding.

The risk of bleeding is highest in elderly and debilitated patients, patients with impaired liver function, and individuals with inadequate nutrition.

In such patients, prothrombin time should be monitored.

Administration of vitamin K corrects hypoprothrombinemia.

In some patients, pseudomembranous colitis caused by toxins produced by Clostridium difficile may develop during or after the use of ceftazidime.

The severity can range from mild to life-threatening.

Therefore, it is important to consider the possibility of pseudomembranous colitis in patients with diarrhea during or after drug use.

In mild cases, drug withdrawal is sufficient, and in more severe cases, restoration of water-electrolyte and protein balance is recommended; metronidazole, bacitracin, or vancomycin are prescribed.

The use of drugs that inhibit intestinal peristalsis is contraindicated.

Long-term use of broad-spectrum antibacterial drugs, including ceftazidime, may lead to overgrowth of non-susceptible microorganisms (e.g., Enterococci, Candida), which may require discontinuation of treatment or appropriate therapy.

The patient’s condition should be constantly assessed during treatment.

As with treatment with other broad-spectrum beta-lactam antibacterial drugs, resistance may develop in some initially susceptible strains of microorganisms (e.g., Enterobacter spp., Pseudomonas spp., Serratia spp.) during the use of ceftazidime.

Therefore, when treating infections caused by these microorganisms, susceptibility testing to antibacterial drugs should be performed periodically.

A false-positive Coombs test and a false-positive urine glucose reaction (Benedict’s test, Fehling’s test, Clinitest) are possible.

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

During treatment, ethanol should not be consumed due to the possibility of disulfiram-like reactions (sudden facial flushing, spasmodic abdominal pain, nausea, vomiting, headache, tachycardia, shortness of breath).

Effect on the ability to drive vehicles, machinery

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

Overdose

Symptoms dizziness, paresthesia, headache, seizures, deviations in laboratory test results.

Treatment since there is no specific antidote, treatment is symptomatic and supportive.

The concentration of ceftazidime in the blood can be reduced by hemodialysis.

Drug Interactions

Pharmaceutically incompatible with aminoglycosides (significant mutual inactivation: when used simultaneously, these drugs should be administered into different parts of the body), vancomycin (forms a precipitate depending on the concentration; if it is necessary to administer two drugs through one tube, the intravenous system should be flushed between their applications).

Do not use sodium bicarbonate solution as a solvent! Pharmaceutically compatible with the following solutions: at a concentration from 1 to 40 mg/ml – 0.9% sodium chloride solution; sodium lactate solution; Hartmann’s solution; 5% dextrose solution; 0.225% sodium chloride and 5% dextrose solution; 0.45% sodium chloride and 5% dextrose solution: 0.9% sodium chloride and 5% dextrose solution; 0.18% sodium chloride and 4% dextrose solution; 10% dextrose solution; 10% dextran with a molecular weight of 40 thousand daltons in 0.9% sodium chloride solution or in 5% dextrose solution; 6% dextran with a molecular weight of 70 thousand daltons in 0.9% sodium chloride solution or in 5% dextrose solution.

At a concentration from 0.05 to 0.25 mg/ml, Ceftazidime is compatible with intraperitoneal dialysis solution (lactate).

For intramuscular injection, Ceftazidime can be diluted with 0.5% or 1% lidocaine hydrochloride solution (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 0.9% sodium chloride solution or in 5% dextrose solution: 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 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 injections) and metronidazole (500 mg/100 ml), both components retain their activity.

Loop diuretics, aminoglycosides, vancomycin, clindamycin reduce the clearance of ceftazidime, resulting in an increased risk of nephrotoxic effects.

Bacteriostatic antibiotics (including chloramphenicol) reduce the effectiveness of the drug.

Ceftazidime can disrupt the intestinal flora, which may lead to decreased reabsorption of estrogens and reduced effectiveness of combined oral contraceptives.

Storage Conditions

In a place protected from light at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

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

Dispensing Status

Dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.