Ceftazidime

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEFTAZIDIME (CEFTAZIDIME)

Composition:

Active substance:
ceftazidime;

1 vial contains 1 g of ceftazidime (as sterile ceftazidime pentahydrate, calculated as 100% dry ceftazidime);

Excipient:
sodium carbonate.

Pharmaceutical form.
Powder for solution for injection.

Main physicochemical properties:
white or slightly yellowish powder.

Pharmacotherapeutic group.
Antibacterials for systemic use. Other
β-lactam antibiotics. Third-generation cephalosporins. Ceftazidime. ATC code J01DD02.

Pharmacological properties.

Pharmacodynamics.

Ceftazidime is a bactericidal cephalosporin antibiotic whose mechanism of action is related to inhibition of bacterial cell wall synthesis.

Acquired resistance to the antibiotic varies between different regions and may change over time, with significant differences observed among individual strains. It is advisable to use local (regional) data on antibiotic susceptibility and prevalence of microorganisms producing extended-spectrum β-lactamases, especially when treating severe infections.

Susceptible microorganisms

Gram-positive aerobes:
Streptococcus pyogenes,
Streptococcus agalactiae.

Gram-negative aerobes:
Citrobacter koseri,
Haemophilus influenzae,
Moraxella catarrhalis,
Neisseria meningitidis,
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 pneumoniae,
Viridans group streptococcus.

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

Gram-negative anaerobes:
Fusobacterium spp..

Resistant 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.

After intramuscular injection of 500 mg and 1 g of ceftazidime, mean peak serum concentrations of 18 mg/L and 37 mg/L are rapidly achieved, respectively. Within 5 minutes after intravenous bolus administration of 500 mg, 1 g, or 2 g of ceftazidime, mean serum concentrations of 46 mg/L, 87 mg/L, or 170 mg/L are achieved, respectively. Therapeutically effective concentrations persist in serum for up to 8–12 hours after intravenous or intramuscular administration. Plasma protein binding is approximately 10%. Concentrations exceeding the minimum inhibitory concentration (MIC) for most common pathogenic microorganisms are achieved in the following tissues and fluids: bone, heart, bile, sputum, intraocular fluid, synovial fluid, pleural fluid, and peritoneal fluid. Ceftazidime rapidly crosses the placenta and is excreted into breast milk. The drug poorly penetrates the intact blood-brain barrier; in the absence of inflammation, CNS concentrations are low. However, during meningitis, ceftazidime concentrations in the CNS reach 4–20 mg/L or higher, which corresponds to therapeutic levels.

Ceftazidime is not metabolized in the body. After parenteral administration, high and sustained serum concentrations are achieved. The elimination half-life is approximately 2 hours. The drug is excreted unchanged in active form in urine via glomerular filtration, with approximately 80–90% of the dose eliminated within 24 hours. In patients with impaired renal function, ceftazidime elimination is reduced, and dosage adjustment is required. Less than 1% of the drug is excreted in bile, significantly limiting the amount reaching the intestinal tract.

Mild to moderate hepatic impairment did not affect ceftazidime pharmacokinetics in subjects receiving 2 g intravenously every 8 hours for 5 days, provided normal renal function (see section "Special precautions").

Reduced clearance observed in elderly patients was primarily associated with age-related decline in renal clearance of ceftazidime. Mean elimination half-life ranged from 3.5 to 4 hours after a single dose or 7-day repeated dosing of 2 g intravenous bolus injections in elderly patients (aged 80 years).

The elimination half-life of ceftazidime is prolonged in premature and full-term neonates by 4.5–7.5 hours after doses of 25–30 mg/kg. However, by the age of 2 months, the elimination half-life falls within the adult range.

Clinical characteristics.

Indications.

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

• Hospital-acquired pneumonia;
• Respiratory tract infections in patients with cystic fibrosis;
• Bacterial meningitis;
• Chronic suppurative otitis media;
• Malignant external otitis;
• Complicated urinary tract infections;
• Complicated skin and soft tissue infections;
• Complicated intra-abdominal infections;
• Bone and joint infections;
• Peritonitis associated with dialysis in patients undergoing continuous ambulatory peritoneal dialysis.

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

Ceftazidime may be used for the treatment of febrile neutropenia in patients resulting from bacterial infection.

Ceftazidime may be used for prophylaxis of urinary tract infections during urological procedures (transurethral resection of the prostate).

When prescribing ceftazidime, consideration should be given to its antibacterial spectrum, which is primarily directed against Gram-negative aerobes (see sections "Pharmacological properties" and "Special precautions").

Ceftazidime should be used in combination with other antibacterial agents if the causative microorganisms of the infection are expected to fall outside the spectrum of ceftazidime activity.

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

Contraindications.

• Hypersensitivity to ceftazidime pentahydrate or to any of the excipients of the medicinal product.
• Hypersensitivity to other cephalosporin antibiotics.
• History of severe hypersensitivity (e.g., anaphylactic reactions) to other β-lactam antibiotics (penicillins, monobactams, and carbapenems).

Interaction with other medicinal products and other forms of interaction.

• Nephrotoxic agents:* Concomitant treatment with high doses of cephalosporins and nephrotoxic medicinal products such as aminoglycosides or potent diuretics (e.g.,
• furosemide*), may adversely affect renal function. If combination therapy is necessary, renal function should be monitored throughout the treatment course (also see section "Incompatibilities").

Chloramphenicol in vitro is an antagonist of ceftazidime and other cephalosporins. The clinical significance of this phenomenon is unknown; however, when administering Ceftazidime concomitantly with chloramphenicol, the possibility of antagonism should be considered.

Concomitant use of bacteriostatic antibiotics may interfere with the action of beta-lactam antibiotics.

Like other antibiotics, ceftazidime may affect intestinal flora, leading to reduced reabsorption of estrogens and decreased efficacy of combined per oral contraceptives.

Therefore, it is recommended to use alternative non-hormonal methods of contraception.

Ceftazidime does not interfere with enzymatic methods for glucose detection in urine; however, a slight interference may occur when using copper reduction methods (Benedict, Fehling, Clinistix).

Ceftazidime does not interfere with the alkaline picrate method for creatinine determination.

Special precautions.

Hypersensitivity

As with other β-lactam antibiotics, severe and occasionally fatal hypersensitivity reactions have been reported. If an allergic reaction occurs, administration of the drug must be discontinued immediately. Severe hypersensitivity reactions may require administration of epinephrine, antihistamines, corticosteroids, and other emergency measures.

Prior to initiating therapy, patients should be questioned about previous hypersensitivity reactions to ceftazidime, cephalosporin antibiotics, penicillins, or other β-lactam antibiotics. The drug should be administered with caution to patients who have experienced mild hypersensitivity reactions to other β-lactam antibiotics.

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCAR), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported during ceftazidime treatment (frequency unknown), which may be life-threatening or fatal. Patients should be informed about the signs and symptoms, and closely monitored for skin reactions. If signs or symptoms suggestive of these reactions occur, ceftazidime should be discontinued immediately and alternative therapy considered. If a patient develops a serious reaction such as SJS, TEN, DRESS, or AGEP during ceftazidime treatment, ceftazidime therapy must not be restarted in this patient at any time.

Spectrum of antibacterial activity

Ceftazidime has a limited antibacterial spectrum. It should not be used as monotherapy for the treatment of certain types of infections, except when the causative pathogen has been documented and is known to be susceptible to this drug, or when there is a high probability that the most likely pathogen will be susceptible to ceftazidime. This is particularly important when considering treatment of patients with bacteremia, bacterial meningitis, skin and soft tissue infections, or bone and joint infections. Furthermore, ceftazidime is susceptible to hydrolysis by some extended-spectrum β-lactamases. Therefore, when selecting ceftazidime for treatment, information regarding the prevalence of microorganisms producing extended-spectrum β-lactamases should be taken into account.

Renal function impairment

Concomitant treatment with high doses of cephalosporins and nephrotoxic agents such as aminoglycosides or potent diuretics (e.g., furosemide) may adversely affect renal function. This is unlikely when recommended dosages are followed. There are no data on negative effects of ceftazidime on renal function when used at usual therapeutic doses.

Ceftazidime is eliminated by the kidneys; therefore, the dose should be adjusted according to the degree of renal impairment. Cases of neurological complications have been reported when the dose was not appropriately reduced.

Overgrowth of non-susceptible microorganisms

As with other broad-spectrum antibiotics, prolonged treatment with ceftazidime may result in overgrowth of non-susceptible microorganisms (e.g., Candida, Enterococci). In such cases, treatment should be discontinued and appropriate measures taken. Close monitoring of the patient is essential.

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

Pseudomembranous colitis

Cases of pseudomembranous colitis, ranging in severity from mild to life-threatening, have been reported during antibiotic therapy. Therefore, pseudomembranous colitis should be considered in patients who develop diarrhea during or after antibiotic administration. If prolonged and severe diarrhea occurs, or if abdominal cramps develop, treatment should be discontinued immediately, further diagnostic evaluation performed, and specific therapy for Clostridium difficile initiated if necessary. Medications that inhibit intestinal motility should not be prescribed.

Sodium content

Ceftazidime contains sodium: 1 vial with 1 g ceftazidime contains ~51 mg of sodium, which should be considered when treating patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Data on ceftazidime use in pregnant women are limited. Animal studies do not indicate any direct or indirect harmful effects on pregnancy, embryonal or postnatal development. The drug should be administered to pregnant women only if the expected benefit outweighs the potential risk.

Ceftazidime is excreted in breast milk in small amounts, but no effects on the breastfed infant are expected when therapeutic doses are used. Ceftazidime may be used during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Dizziness and seizures may occur in some patients. Therefore, caution should be exercised when driving or operating potentially hazardous machinery requiring high concentration and rapid psychomotor reactions during treatment.

Method of administration and dosage.

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

Table 1

Adults and children ≥ 40 kg

Intermittent administration
Infection	Dose administered
respiratory tract infections in patients with cystic fibrosis	100–150 mg/kg body weight per day every 8 hours, up to a maximum of 9 g per day1
febrile neutropenia	2 g every 8 hours
hospital-acquired pneumonia
bacterial meningitis
bacteremia*
bone and joint infections	1–2 g every 8 hours
complicated skin and soft tissue infections
complicated intra-abdominal infections
peritonitis associated with continuous ambulatory peritoneal dialysis
complicated urinary tract infections	1–2 g every 8 or 12 hours
urinary tract infections during surgery on the prostate gland (transurethral resection)	1 g at induction of anesthesia, 1 g at the time of catheter removal
chronic suppurative otitis media	1–2 g every 8 hours
malignant external otitis
Continuous infusion
Infection	Dose administered
febrile neutropenia	A loading dose of 2 g is administered, followed by continuous infusion of 4 to 6 g every 24 hours1
hospital-acquired pneumonia
respiratory tract infections in patients with cystic fibrosis
bacterial meningitis
bacteremia*
bone and joint infections
complicated skin and soft tissue infections
complicated intra-abdominal infections
peritonitis associated with continuous ambulatory peritoneal dialysis
1 In adult patients with normal renal function, administration of up to 9 g of the drug per day did not cause adverse reactions.

*If this is associated with or there is suspicion of association with infections listed in the section "Indications".

Table 2

Children < 40 kg

Infants and children older than 2 months of age and weighing less than 40 kg	Infection	Usual dose
Intermittent administration
	complicated urinary tract infections	100–150 mg/kg body weight per day in 3 divided doses, maximum 6 g per day
	chronic otitis media
	malignant external otitis
	neutropenia in children	150 mg/kg body weight per day in 3 divided doses, maximum 6 g per day
	respiratory tract infections in patients with cystic fibrosis
	bacterial meningitis
	bacteremia*
	bone and joint infections	100–150 mg/kg body weight per day in 3 divided doses, maximum 6 g per day
	complicated skin and soft tissue infections
	complicated intra-abdominal infections
	peritonitis associated with continuous ambulatory peritoneal dialysis
Continuous infusion
	febrile neutropenia	A loading dose of 60–100 mg/kg body weight is administered, followed by continuous intravenous infusion of 100–200 mg/kg body weight per day, up to a maximum of 6 g per day
	hospital-acquired pneumonia
	respiratory tract infections in patients with cystic fibrosis
	bacterial meningitis
	bacteremia*
	bone and joint infections
	complicated skin and soft tissue infections
	complicated intra-abdominal infections
	peritonitis associated with continuous ambulatory peritoneal dialysis
Infants aged ≤ 2 months	Infection	Usual dose
Intermittent administration
	most infections	25–60 mg/kg body weight per day in 2 divided doses1
1In infants and children aged ≤ 2 months, the serum half-life may be 2–3 times longer than in adults

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

Children

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

Elderly patients

Due to reduced clearance of ceftazidime, the daily dose should not exceed 3 g in elderly patients with acute infections, particularly in patients aged 80 years and older.

Hepatic impairment

Dosage adjustment is not required in patients with mild to moderate hepatic impairment. Clinical studies in patients with severe hepatic impairment have not been conducted. Close clinical monitoring of efficacy and safety of the drug is recommended in these patients.

Renal impairment

Ceftazidime is excreted unchanged by the kidneys; therefore, the dose should be reduced in this patient group.

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

Recommended maintenance doses of ceftazidime in renal impairment –

intermittent administration

Table 3

Adults and children ≥ 40 kg body weight

Creatinine clearance, mL/min	Approximate serum creatinine level, µmol/L (mg/dL)	Recommended single dose of ceftazidime, g	Dosing interval (hours)
50–31	150–200 (1.7–2.3)	1	12
30–16	200–350 (2.3–4)	1	24
15–6	350–500 (4–5.6)	0.5	24
< 5	> 500 (> 5.6)	0.5	48

For patients with severe infections, the single dose may be increased by 50%, or the frequency of administration may be increased accordingly. In such patients, monitoring of ceftazidime serum levels is recommended.

In children, creatinine clearance values should be adjusted according to body surface area or body weight.

Table 4

Children < 40 kg

Creatinine clearance, ml/min**	Approximate serum creatinine level* in blood, μmol/L (mg/dL)	Recommended individual dose, mg/kg body weight	Dosing frequency (hours)
50–31	150–200 (1.7–2.3)	25	12
30–16	200–350 (2.3–4)	25	24
15–6	350–500 (4–5.6)	12.5	24
< 5	> 500 (> 5.6)	12.5	48

*This is the serum creatinine level calculated according to recommendations and may not precisely reflect the degree of renal function impairment in all patients with renal insufficiency.

**Creatinine clearance is estimated based on body surface area or measured directly.

Careful clinical monitoring of patients is recommended to assess the efficacy and safety of the drug.

Recommended maintenance doses of ceftazidime in renal insufficiency – continuous infusion

Table 5

Adults and children ≥ 40 kg body weight

Creatinine clearance, mL/min	Approximate serum creatinine level, μmol/L (mg/dL)	Dosing frequency (hours)
50–31	150–200 (1.7–2.3)	A loading dose of 2 g is administered, followed by continuous infusion of 1–3 g every 24 hours
30–16	200–350 (2.3–4)	A loading dose of 2 g is administered, followed by continuous infusion of 1 g every 24 hours
≤ 15	> 350 (4–5.6)	Not studied

Dose selection should be cautious. Careful clinical monitoring of patients is recommended for the efficacy and safety of the drug use.

Children < 40 kg

The safety and efficacy of Ceftazidime administered by continuous intravenous infusion in children with body weight < 40 kg and impaired renal function have not been established. Careful clinical monitoring of patients is recommended.

If children with impaired renal function require administration of the drug by continuous intravenous infusion, creatinine clearance should be adjusted according to the child's body surface area or body weight.

Hemodialysis

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

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

Peritoneal dialysis

Ceftazidime can be used during peritoneal dialysis and continuous ambulatory peritoneal dialysis in the usual regimen.

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

For patients with renal insufficiency undergoing prolonged arteriovenous hemodialysis or high-flux hemofiltration in intensive care units, the recommended dose is 1 g per day as a single dose or divided into several doses. For low-flux hemofiltration, doses should be adjusted as in renal impairment.

For patients undergoing venovenous hemofiltration and venovenous hemodialysis, dosing recommendations are provided in tables 6–7.

Table 6

Dosing recommendations for ceftazidime in patients undergoing prolonged
venovenous hemofiltration

Residual kidney function (creatinine clearance, mL/min)	Maintenance dose (mg) depending on ultrafiltration rate (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

*Note. The maintenance dose should be administered every 12 hours.

Table 7

Dosing recommendations for ceftazidime in patients undergoing prolonged
hemodialysis

Residual renal function (creatinine clearance, mL/min)	Maintenance dose (mg) according to ultrafiltration rate (mL/min)*
	1 L/h			2 L/h
	Ultrafiltration rate (L/h)			Ultrafiltration rate (L/h)
	0.5	1	2	0.5	1	2
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

* The maintenance dose should be administered every 12 hours.

Administration

Ceftazidime must be administered intravenously or by deep intramuscular injection. Recommended sites for intramuscular administration are the upper outer quadrant of the gluteal muscle or the lateral part of the thigh.

Ceftazidime solutions may be administered directly into the vein or into an intravenous infusion system if the patient is receiving parenteral fluids.

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

Acquired resistance to the antibiotic varies among different regions and may change over time, and significant differences may exist among individual strains. Local (regional) data on antibiotic susceptibility should preferably be used, especially when treating severe infections.

Preparation instructions

Ceftazidime is compatible with most commonly used intravenous infusion solutions; however, sodium bicarbonate for injection should not be used as a solvent (see section "Incompatibilities").

Table 8

Dose administered		Required amount of solvent (ml)	Approximate concentration (mg/ml)
1 g	Intramuscular	3	260
	Intravenous bolus	10	90
	Intravenous infusion	50*	20

*Note. Reconstitution should be performed in two steps (see text).

The color of the solution varies from light yellow to amber depending on concentration, diluent, and storage conditions. Provided that the recommendations are followed, the activity of the drug does not depend on variations in its coloration.

Ceftazidime at concentrations from 1 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 in 5% glucose solution; 0.45% sodium chloride in 5% glucose solution; 0.9% sodium chloride in 5% glucose solution; 0.18% sodium chloride in 4% glucose solution; 10% glucose solution; 10% dextran 40 in 0.9% sodium chloride solution; 10% dextran 40 in 5% glucose solution; 6% dextran 70 in 0.9% sodium chloride solution; 6% dextran 70 in 5% glucose solution.

Ceftazidime at concentrations from 0.05 to 0.25 mg/mL is compatible with peritoneal dialysis fluid (lactate).

For intramuscular administration, ceftazidime should be reconstituted with 0.5% or 1% lidocaine solution.

The stability of both agents is maintained when ceftazidime at a concentration of 4 mg/mL is mixed with the following agents: hydrocortisone (hydrocortisone sodium phosphate) 1 mg/mL in 0.9% sodium chloride solution or 0.5% glucose 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 5 IU/mL in 0.9% sodium chloride solution; potassium chloride 10 mEq/L or 40 mEq/L in 0.9% sodium chloride solution.

Preparation of solutions for intramuscular or intravenous bolus injection

Insert the needle of the syringe through the vial stopper and inject the recommended volume of diluent.

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. Withdraw the entire solution into the syringe, keeping the needle tip submerged in the solution at all times. Small bubbles of carbon dioxide may be disregarded.

Preparation of solutions for intravenous infusion

Insert the needle of the syringe through the vial stopper and inject 10 mL of diluent.

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

Do not insert an air vent needle through the stopper until the drug is completely dissolved. Insert an air vent needle through the stopper into the vial to relieve internal pressure.

Without removing the air vent needle, adjust the total volume to 50 mL. Remove the air vent needle, shake the vial, and set up the infusion system as usual. Administer by intravenous infusion over 15–30 minutes.

Note. To ensure sterility of the preparation, it is essential not to insert the air vent needle through the stopper before the drug is fully dissolved.

Children.

Can be used in neonates from the first days of life.

Overdose.

Symptoms: neurological complications such as encephalopathy, seizures, and coma may occur. Symptoms of overdose may appear in patients with renal insufficiency if the dose is not reduced. Serum concentrations of ceftazidime can be reduced by hemodialysis or peritoneal dialysis.

Treatment: symptomatic.

Adverse Reactions

The most commonly observed adverse reactions are eosinophilia, thrombocytosis, phlebitis or thrombophlebitis following intravenous administration, diarrhea, transient elevation of liver enzymes, maculopapular or urticarial rash, pain and/or inflammation at the site of intramuscular injection, and a positive Coombs test. Data from both sponsor- and non-sponsor-initiated clinical trials were used to determine the frequency of common and rare adverse effects. Frequencies associated with all other adverse reactions were primarily derived from post-marketing data and refer to reporting rates rather than true incidence. Within each group, adverse reactions are listed in order of decreasing severity.

Adverse reactions have been classified according to frequency of occurrence — from very common to uncommon — and by organ systems: 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 not known (cannot be estimated from available data).

Infections and infestations

Uncommon – candidiasis (including vaginitis and candidal stomatitis).

Blood and lymphatic system disorders

Common – eosinophilia and thrombocytosis.

Uncommon – leukopenia, neutropenia, and thrombocytopenia.

Frequency not known – lymphocytosis, hemolytic anemia, agranulocytosis.

Immune system disorders

Frequency not known – anaphylaxis (including bronchospasm and/or arterial hypotension).

Nervous system disorders

Uncommon – dizziness, headache.

Frequency not known – paresthesia.

Neurological complications such as tremor, myoclonia, seizures, encephalopathy, and coma have been reported in patients with renal impairment who did not receive appropriate dose reductions of ceftazidime.

Vascular disorders

Common – phlebitis or thrombophlebitis at the injection site.

Gastrointestinal disorders

Common – diarrhea.

Uncommon – nausea, vomiting, abdominal pain, and colitis.

As with other cephalosporins, colitis may be related to Clostridium difficile and may present as pseudomembranous colitis (see section "Special precautions").

Frequency not known – taste disturbances.

Renal and urinary disorders

Uncommon – transient increases in blood urea, blood urea nitrogen, and/or serum creatinine levels.

Very rare – interstitial nephritis, acute renal failure.

Hepatobiliary disorders

Common – transient elevation of one or more liver enzymes (ALT, AST, LDH, GGT, alkaline phosphatase).

Frequency not known – jaundice.

Skin and subcutaneous tissue disorders

Common – maculopapular rash or urticaria.

Uncommon – pruritus.

Frequency not known – angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP).

General disorders and administration site conditions

Common – pain and/or inflammation at the site of intramuscular injection.

Uncommon – fever.

Investigations

Common – positive Coombs test. A positive Coombs reaction occurs in approximately 5% of patients and may interfere with blood grouping.

Uncommon – as with some other cephalosporins, transient increases in blood urea, blood urea nitrogen, and/or serum creatinine levels have occasionally been observed.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://аіsf.dec.gov.ua.

Shelf life.
3 years.

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

Keep out of reach of children.

The reconstituted solution remains stable for 10 hours at 25 °C, for 24 hours at temperatures not exceeding 18 °C, and for 7 days at temperatures up to 4 °C.

From a microbiological standpoint, the reconstituted solution should be used immediately. If immediate use is not possible, the solution may be stored for up to 24 hours at 2–8 °C.

Incompatibilities.

Ceftazidime is less stable in sodium bicarbonate injection solution than in other intravenous solutions and therefore is not recommended as a solvent.

Ceftazidime and aminoglycosides should not be mixed in the same infusion system or syringe.

Precipitation may occur if vancomycin is added to a ceftazidime solution. Therefore, infusion systems and intravenous catheters should be flushed between administration of these two agents.

Ceftazidime solution must not be mixed in the same container with other antibiotics.

Packaging.
1 vial per pack. 1 vial in a carton.

Prescription status.
Prescription only.

Manufacturer: Public Joint-Stock Company "Scientific and Production Center "Borshchahivskyy Chemical and Pharmaceutical Plant".

Manufacturer's address and location of operations
17 Myru Street, Kyiv, 03134, Ukraine.