Ceftazidime

INSTRUCTIONS for medical use of the medicinal product CEFTAZIDIME (CEFTAZIDIME)

Composition:

active substance: ceftazidime (ceftazidime);

1 vial contains ceftazidime (as ceftazidime pentahydrate) 1 g;

excipient: sodium carbonate.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white or slightly yellow powder.

Pharmacotherapeutic group. Antibacterials for systemic use. β-lactam antibiotics. Third-generation cephalosporins. ATC code J01D D02.

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

Acquired resistance to the antibiotic varies across different regions and may change over time, with significant differences possible among individual strains. It is advisable to use local data on antibiotic susceptibility and the 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.

Strainswithpossibleacquiredresistance

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, Streptococcus pneumoniae, Viridans group streptococci.

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

Gram-negative anaerobes: Fusobacterium spp.

Resistantmicroorganisms

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.

Absorption. After intramuscular administration of 500 mg and 1 g of ceftazidime, peak plasma concentrations of 18 and 37 mg/L, respectively, are rapidly achieved. Within 5 minutes after intravenous bolus administration of 500 mg, 1 g, or 2 g, plasma concentrations are 46, 87, and 170 mg/L, respectively. The pharmacokinetics of ceftazidime are linear over the single-dose range of 0.5 to 2 g following either intravenous or intramuscular administration.

Distribution. Plasma protein binding of ceftazidime is low, approximately 10%. Concentrations exceeding the MIC for common pathogenic microorganisms can be achieved in tissues such as bone, heart, bile, sputum, aqueous eye fluid, synovial, pleural, and peritoneal fluids. Ceftazidime readily crosses the placenta and is excreted into breast milk. Penetration across the intact blood-brain barrier is poor, resulting in low ceftazidime levels in the central nervous system (CNS) in the absence of inflammation. However, during meningitis, concentrations in the CNS reach 4 to 20 mg/L or higher, achieving therapeutic levels.

Biotransformation. Ceftazidime is not metabolized.

Elimination. After parenteral administration, plasma concentrations decline with a half-life (t½) of approximately 2 hours. Ceftazidime is excreted unchanged in urine via glomerular filtration; approximately 80% to 90% of the administered dose is recovered in urine within 24 hours. Less than 1% is excreted in bile. In patients with impaired renal function, elimination of ceftazidime is reduced, and dosage adjustment is required.

Clinical characteristics.

Indications.

Treatment of 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 chronic ambulatory peritoneal dialysis (CAPD).

Treatment of patients with bacteremia that arises in connection with any of the above-mentioned infections or is likely related to them.

Ceftazidime may be used for the treatment of patients with neutropenia and fever resulting from bacterial infection.

Ceftazidime may be used for perioperative prophylaxis of urinary tract infections in patients undergoing transurethral resection of the prostate (TURP).

When prescribing ceftazidime, its antibacterial spectrum directed primarily against Gram-negative aerobes should be taken into account (see sections «Special precautions for use» and «Pharmacological properties» ).

Ceftazidime should be administered in combination with other antibacterial agents when the range of bacteria causing the infection may fall outside the spectrum of activity of ceftazidime.

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

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

Concomitant use of high doses with nephrotoxic medicinal products may adversely affect renal function (see section «Special precautions for use» ).

Chloramphenicol is an in vitro antagonist of ceftazidime and other cephalosporins. The clinical significance of this finding is unknown, but if concomitant administration of ceftazidime with chloramphenicol is anticipated, antagonism should be considered.

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

Ceftazidime does not interfere with enzymatic methods for glucose testing in urine and causes minimal interference with methods based on copper reduction (Benedict's test, Fehling's test, Clinitest).

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

Special precautions.

Increased sensitivity.

As with other β-lactam antibiotics, severe and sometimes fatal hypersensitivity reactions have been reported. In the event of severe hypersensitivity reactions, ceftazidime therapy should be discontinued immediately and appropriate emergency measures initiated.

Prior to initiating therapy, patients should be questioned about previous hypersensitivity reactions to ceftazidime, other cephalosporin antibiotics, 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 skin adverse reactions (SSARs), 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 treatment with ceftazidime. These reactions may be life-threatening or fatal, with an incidence rate described as "unknown."

Patients should be informed about the signs and symptoms of such reactions, and careful monitoring for skin reactions is required.

If signs or symptoms suggestive of these reactions occur, ceftazidime should be discontinued immediately, and alternative therapy should be considered.

If a serious reaction such as SJS, TEN, DRESS, or AGEP develops during ceftazidime treatment, re-administration of ceftazidime is absolutely contraindicated.

Spectrum of activity.

Ceftazidime has a limited antibacterial spectrum. It is not an appropriate agent for monotherapy of certain types of infections, except when the causative pathogen is known and demonstrated to be susceptible to ceftazidime, or when there is a high likelihood that the pathogen will be susceptible. This is particularly important when considering treatment of patients with bacteremia, bacterial meningitis, skin and soft tissue infections, and bone and joint infections.

Furthermore, ceftazidime is susceptible to hydrolysis by several extended-spectrum β-lactamases (ESBLs). Therefore, when selecting ceftazidime for therapy, information regarding the prevalence of ESBL-producing organisms should be taken into account.

Pseudomembranous colitis.

Cases of pseudomembranous colitis have been reported with antibiotic use, with severity ranging from mild to life-threatening. It is important to consider this diagnosis in patients who develop diarrhea during or after ceftazidime therapy. If diarrhea is persistent and severe, or if abdominal cramps occur, 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 administered.

Renal function.

Concomitant therapy with high doses of cephalosporins and nephrotoxic agents 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 recommended dosages are followed. There is no evidence that ceftazidime adversely affects renal function at usual therapeutic doses.

Ceftazidime is eliminated by the kidneys; therefore, dosage should be adjusted according to the degree of renal impairment. Cases of neurological complications have been reported when dosage was not appropriately reduced (see sections «Dosage and administration» and «Adverse reactions»).

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, discontinuation of therapy or appropriate interventions may be necessary. Continuous monitoring of the patient is essential.

As with other broad-spectrum 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.

Sodium content. The product contains sodium (1 g ceftazidime – 52 mg sodium or 2.26 mmol per vial), which should be considered when treating patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy. 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. Ceftazidime should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breastfeeding. Ceftazidime passes into breast milk in small amounts, but no effects on the infant are expected at therapeutic doses. Ceftazidime may be used during breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

No specific studies have been conducted. However, certain adverse reactions (e.g., dizziness) may occur, which could affect the ability to drive or operate machinery (see section «Adverse reactions»).

Method of administration and dosage.

Adults and children with body weight ≥40 kg.

Table 1

Intermittent administration
Infection	Dose administered
Respiratory tract infections in patients with cystic fibrosis	100–150 mg/kg body weight per day every 8 hours, maximum 9 g per day 1
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 CAPD dialysis
Complicated urinary tract infections	1–2 g every 8 or 12 hours
Perioperative prophylaxis of transurethral resection of the prostate	1 g at the time of anesthesia induction, 1 g at the time of catheter removal
Chronic otitis media	1–2 g every 8 hours
Malignant external otitis
Continuous infusion
Infectious disease	Dose administered
Febrile neutropenia	A loading dose of 2 g is administered, followed by continuous infusion of 4 to 6 g every 24 hours 1
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 9 g of the drug per day did not cause adverse reactions. * In cases where they are associated with, or likely related to, any infection listed in the section "Indications".

Children with body weight <40 kg.

Table 2

Infants and children aged 2 months and older with body weight <40 kg	Infection	Usual dose
Intermittent administration
	complicated urinary tract infections	100–150 mg/kg body weight per day given in 3 divided doses, maximum 6 g per day
	chronic suppurative otitis media
	malignant external otitis
	neutropenia in children	150 mg/kg body weight per day given in 3 divided doses, maximum 6 g per day
	respiratory tract infections in patients with cystic fibrosis
	bacterial meningitis
	bacteraemia *
	bone and joint infections	100–150 mg/kg body weight per day given 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	An initial loading dose is administered followed by continuous 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
	bacteraemia *
	bone and joint infections
	complicated skin and soft tissue infections
	complicated intra-abdominal infections
	dialysis-associated peritonitis (CAPD)
Infants aged ≤2 months	Infection	Usual dose
Intermittent administration
	Most infections	25–60 mg/kg body weight per day given in 2 divided doses1
1 In infants and children aged ≤2 months, the t½ of ceftazidime in serum may be 2–3 times longer than in adults. * When associated or likely associated with any infection listed in the section “Indications”.

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

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

Hepatic impairment. Dose adjustment is not required in patients with mild to moderate hepatic impairment. Clinical studies in patients with severe hepatic impairment have not been conducted. Careful clinical monitoring of efficacy and safety is recommended.

Renal impairment. Ceftazidime is eliminated 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 creatinine clearance.

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

Adults and children with body weight ≥40 kg.

Table 3

Creatinine clearance, mL/min	Approximate serum creatinine level, µmol/L (mg/day)	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 correspondingly increased. In such patients, monitoring of ceftazidime serum levels is recommended.

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

Children with body weight <40 kg.

Table 4

Creatinine clearance, ml/min**	Approximate serum creatinine* level, µmol/L (mg/day)	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

* Serum creatinine level, calculated according to recommendations, may not accurately reflect the degree of renal function impairment in all patients with renal insufficiency.

** Creatinine clearance, calculated based on body surface area or measured.

Careful clinical monitoring of efficacy and safety of administration is recommended.

Recommended maintenance doses of ceftazidime in renal insufficiency: continuous infusion.

Adults and children with body weight ≥40 kg.

Table 5

Creatinine clearance, mL/min	Approximate serum creatinine level, µmol/L (mg/day)	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)	Not studied

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

Children with body weight <40 kg.

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

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

Hemodialysis. The half-life (t½) of ceftazidime in serum during hemodialysis is 3 to 5 hours.

After each hemodialysis session, a maintenance dose of ceftazidime as recommended in the table below should be administered.

Peritoneal dialysis. Ceftazidime can be used during peritoneal dialysis in standard regimens and during continuous ambulatory peritoneal dialysis.

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 daily as a single dose or divided doses. For low-flux hemofiltration, doses should be used as in renal impairment.

Dosing recommendations for patients undergoing venovenous hemofiltration and venovenous hemodialysis are provided in the tables below.

Dosing recommendations for ceftazidime in patients undergoing prolonged venovenous hemofiltration.

Table 6

Residual renal function (creatinine clearance, ml/min)	Maintenance dose (mg) depending on ultrafiltration rate (ml/min) a
	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

and the maintenance dose should be administered every 12 hours.

Dosing recommendations for ceftazidime in patients undergoing prolonged venovenous hemodialysis.

Table 7

Residual renal function (creatinine clearance, mL/min)	Maintenance dose (mg) for dialysate at flow rate (mL/min) a
	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

and the maintenance dose should be administered every 12 hours.

Administration. Ceftazidime should be administered intravenously by injection or infusion, 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, with significant differences observed in individual strains. Local antibiotic susceptibility data should preferably be used, especially when treating severe infections.

Preparation of the injection solution. Ceftazidime is compatible with most intravenous infusion solutions. However, sodium bicarbonate for injection should not be used as a solvent (see section «Incompatibilities»).

All vial sizes are manufactured under reduced pressure. As the drug dissolves, carbon dioxide is released, increasing the pressure inside the vial. Small bubbles of carbon dioxide in the reconstituted solution can be disregarded.

Table 8

Dose administered	Route of administration	Required amount of diluent (ml)	Approximate concentration (mg/ml)
1 g	intramuscular intravenous bolus intravenous infusion	3 10 50*	260 90 20

* Reconstitution should be carried out in two steps (see below).

The solution color may vary from light yellow to amber depending on the diluent concentration and storage conditions. The drug's efficacy is not affected by variations in color when recommendations are followed.

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 and 5% glucose solution; 0.45% sodium chloride and 5% glucose solution; 0.9% sodium chloride and 5% glucose solution; 0.18% sodium chloride and 4% glucose solution; 10% glucose solution; 10% glucose 40 and 0.9% sodium chloride solution; 10% glucose 40 and 5% glucose solution; 6% dextran 70 and 0.9% sodium chloride solution; 6% dextran 70 and 5% glucose solution.

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

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

The stability of both agents is maintained when ceftazidime at a concentration of 4 mg/mL is mixed with the following substances: hydrocortisone (hydrocortisone sodium phosphate) 1 mg/mL in 0.9% sodium chloride injection or 0.5% glucose solution; cefuroxime (cefuroxime sodium) 3 mg/mL in 0.9% sodium chloride injection; cloxacillin (cloxacillin sodium) 4 mg/mL in 0.9% sodium chloride injection; heparin 10 or 50 IU/mL in 0.9% sodium chloride injection; potassium chloride 10 or 40 mEq/L in 0.9% sodium chloride injection.

Preparation of solution for intramuscular or intravenous bolus injection.

1. Insert the needle of the syringe through the vial stopper and add the recommended volume of diluent.
2. Remove the syringe needle and shake the vial until a clear solution is obtained.
3. Invert the vial. With the syringe plunger fully depressed, insert the needle into the vial. Withdraw the entire solution into the syringe, ensuring the needle remains submerged in the solution at all times. Small bubbles of carbon dioxide may be disregarded.

Preparation of solution for intravenous infusion.

1. Insert the needle of the syringe through the vial stopper and add 10 mL of diluent.
2. Remove the syringe needle and shake the vial until a clear solution is obtained.
3. Do not insert the needle through the stopper until the drug is completely dissolved. Insert the needle through the stopper into the vial to release internal pressure.
4. Without removing the needle, adjust the total volume to 50 mL. Remove the needle, shake the vial, and prepare the infusion set as usual.

Note. To ensure sterility of the product, it is essential not to insert the needle through the stopper until the drug is fully dissolved.

After reconstitution. After reconstitution, the medicinal product maintains chemical and physical stability for up to 6 days at 4°C and for up to 9 hours at 25°C.

From a microbiological standpoint, the solution should be used immediately. If not used immediately, the responsibility for the duration and conditions of storage prior to use rests with the user. If reconstitution was not performed under controlled and validated aseptic conditions, the solution should be stored for no longer than 24 hours at a temperature of 2–8°C.

After dilution. After dilution, the medicinal product maintains chemical and physical stability for up to 6 days at 4°C and for up to 9 hours at 25°C.

From a microbiological standpoint, the solution should be used immediately after reconstitution and dilution. If not used immediately, the responsibility for the duration and conditions of storage prior to use rests with the user. If dilution was not performed under controlled and validated aseptic conditions, the solution should be stored for no longer than 24 hours at a temperature of 2–8°C.

Children.

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

Overdose.

Overdose may lead to neurological complications such as encephalopathy, seizures, and coma. Symptoms of overdose may occur in patients with renal impairment if the dose is not appropriately reduced (see sections «Dosage and administration» and «Special precautions»).

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

Adverse Reactions

Adverse effects have been classified by organ systems and frequency of occurrence: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); frequency not known.

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, and agranulocytosis.

Immune system disorders:
Frequency not known – anaphylaxis (including bronchospasm and/or arterial hypotension).

Nervous system disorders:
Uncommon – dizziness, headache;
Frequency not known – paresthesia.

Cases of neurological complications such as tremor, myoclonia, seizures, encephalopathy, and coma have been reported in patients with renal impairment who did not receive appropriate dose reduction 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 associated with Clostridium difficile and may present as pseudomembranous colitis (see section "Special precautions").
Frequency not known – taste disturbances.

Renal and urinary disorders:
Uncommon – transient increase in blood urea levels;
Very rare – interstitial nephritis, acute renal failure.

Hepatobiliary disorders:
Common – transient elevation of one or more liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], γ-glutamyltransferase [GGT], alkaline phosphatase);
Frequency not known – jaundice.

Skin and subcutaneous tissue disorders:
Common – maculopapular rash or urticaria;
Uncommon – pruritus;
Frequency not known – angioedema, polymorphic erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP).

General disorders and administration site conditions:
Common – pain and/or inflammation at the site of intramuscular injection;
Uncommon – fever.

Laboratory findings:
Common – positive Coombs test;
Uncommon – transient increase in blood urea, blood urea nitrogen (BUN), and/or serum creatinine levels.
A positive Coombs test occurs in approximately 5% of patients and may interfere with blood grouping.

Reporting of adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and 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://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

No special storage conditions required.

Store in a place inaccessible to children, in the original packaging.

The reconstituted solution can be stored for 24 hours at a temperature below 25°C or for 7 days at a temperature up to 4°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.

When vancomycin solution is added to ceftazidime solution, precipitation may occur; therefore, it is recommended to flush infusion systems and intravenous catheters between administrations of these drugs.

Packaging.
1 g of powder in a vial; packs of 1, 5, or 50 vials; or 1 or 5 vials in a blister pack, 1 blister pack in a carton.

Prescription status. Prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhim-Kharkiv". LLC "Lekhim-Obukhiv".

Manufactured from bulk product supplied by the manufacturer: Reyoung Pharmaceutical Co., Ltd., People's Republic of China.

Manufacturer's address and location of operations.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.

126A Kyivska Street, Obukhiv, Kyiv Oblast, 08700, Ukraine.