Ceftazidime

INSTRUCTION for medical use of the medicinal product Ceftazidime (Ceftazidime)

Composition:

Active substance: ceftazidime;

1 vial contains ceftazidime pentahydrate equivalent to ceftazidime 1000 mg or 2000 mg;

Excipient: sodium carbonate anhydrous.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: crystalline powder, white to cream-colored.

Pharmacotherapeutic group. Antibacterial agent for systemic use. 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 among different regions and may change over time, and may differ significantly among individual strains. It is advisable to use local (regional) data on antibiotic susceptibility and information on the prevalence of microorganisms producing extended-spectrum beta-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.

In patients, after intramuscular injection of 500 mg and 1 g, mean peak serum 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, mean serum concentrations of 46, 87, or 170 mg/L, respectively, are achieved. Therapeutically effective concentrations persist in serum for up to 8–12 hours after intravenous or intramuscular administration. Plasma protein binding is approximately 10%. Therapeutic concentrations exceeding the MIC for most common pathogenic microorganisms are achieved in tissues and body fluids such as bone, heart, bile, sputum, intraocular fluid, synovial, pleural, and peritoneal fluids. Ceftazidime rapidly crosses the placenta and is excreted into breast milk. The drug penetrates poorly across the intact blood-brain barrier; in the absence of inflammation, drug concentrations in the CNS 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 of ceftazidime are achieved. The elimination half-life is approximately 2 hours. The drug is excreted unchanged, in active form, in urine via glomerular filtration; approximately 80–90% of the dose is excreted in urine within 24 hours. In patients with impaired renal function, elimination of ceftazidime 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.

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 patients with neutropenia and fever resulting from bacterial infection.

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

When prescribing ceftazidime, it should be borne in mind that its antibacterial activity is primarily directed against gram-negative aerobes (see sections "Special precautions" and "Pharmacological properties").

Ceftazidime should be used in combination with other antibacterial agents if it is expected that a range of microorganisms causing the infection are not covered by the spectrum of ceftazidime.

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

Contraindications.

Hypersensitivity to ceftazidime or to any of the excipients of the drug.

Hypersensitivity to other 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 medicinal products may adversely affect renal function (see section "Special precautions").

Chloramphenicol is an in vitro antagonist of ceftazidime and other cephalosporins. The clinical significance of this phenomenon is unknown; however, if concomitant administration of the drug with chloramphenicol is proposed, the possibility of antagonism should be considered.

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

Ceftazidime does not interfere with enzymatic methods for determining glucosuria; however, a minor interference may be observed when using copper reduction methods (Benedict, Fehling, Clinitest).

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

Special precautions for use.

Hypersensitivity reactions.

As with other beta-lactam antibiotics, severe and sometimes fatal hypersensitivity reactions have been reported. If severe hypersensitivity reactions occur, ceftazidime therapy must 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 beta-lactam antibiotics. The drug should be administered with caution to patients who have experienced non-severe hypersensitivity reactions to other beta-lactam antibiotics.

Serious 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, and their frequency is considered "unknown."

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 must be discontinued immediately, and alternative therapy should be considered.

If a serious reaction such as SJS, TEN, DRESS, or AGEP develops during ceftazidime treatment, ceftazidime therapy must not be restarted under any circumstances.

Antimicrobial spectrum.

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 to be susceptible to this drug or when there is a high likelihood that the 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. Additionally, ceftazidime is susceptible to hydrolysis by certain extended-spectrum beta-lactamases. Therefore, when selecting ceftazidime for therapy, information regarding the prevalence of microorganisms producing extended-spectrum beta-lactamases should be taken into account.

Renal function.

Concomitant administration of 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 are no data indicating that ceftazidime adversely affects renal function 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 (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 other necessary interventions may be required. Careful monitoring of the patient is essential.

Pseudomembranous colitis.

Cases of pseudomembranous colitis, ranging in severity from mild to life-threatening, have been reported with antibiotic use. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after antibiotic therapy. If prolonged or significant diarrhea occurs, or if abdominal cramps develop, therapy should be discontinued immediately, further diagnostic evaluation should be performed, and specific treatment for Clostridium difficile should be initiated if necessary. Medicinal products that inhibit intestinal peristalsis should not be administered.

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 medicinal product contains sodium (1 vial with 1 g ceftazidime – 52 mg (2.3 mmol) sodium; 1 vial with 2 g ceftazidime – 104 mg (4.6 mmol) sodium), which should be taken into account when treating patients on a sodium-controlled 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 prescribed during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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

Ability to affect reaction speed when driving or operating machinery.

No specific studies have been conducted. However, adverse reactions such as dizziness may 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 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
prophylaxis of postoperative infectious complications in prostate surgery (transurethral resection)	1 g at induction of anesthesia, 1 g at the time of catheter removal
chronic 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 per day did not cause adverse reactions.

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

Children with body weight <40 kg

Table 2.

Infants and children > 2 months of age with body weight < 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 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
1 In infants and children ≤ 2 months of age, 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 administration by continuous intravenous infusion in infants and children aged ≤ 2 months have not been established.

Older patients.

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

Hepatic impairment.

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

Renal impairment.

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

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

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/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

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, 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/dL)	Recommended individual dose, mg/kg body weight	Dosing interval, 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 levels calculated according to recommendations may not precisely reflect the degree of renal function decline in all patients with renal impairment.

** 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 impairment – continuous infusion.

Adults and children with body weight ≥ 40 kg

Table 5.

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 to 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 body weight < 40 kg and impaired renal function 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 necessary in children with impaired renal function, 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 to 5 hours.

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

Peritoneal dialysis.

Ceftazidime can be used during peritoneal dialysis, including 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 per day as a single dose or divided 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.

Dosing recommendations for ceftazidime in patients undergoing prolonged venovenous hemofiltration.

Table 6.

Residual renal function (creatinine clearance, ml/min)	Maintenance dose (mg) according to ultrafiltration rate (ml/min)а
	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.

Dosage 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

The maintenance dose should be administered every 12 hours.

Administration.

The drug 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 gluteus maximus muscle or the lateral aspect 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 dose depends on the severity of the disease, sensitivity, location and type of infection, as well as on the patient's age and renal function.

Instructions for solution preparation.

Ceftazidime is compatible with most commonly used intravenous infusion solutions. However, sodium bicarbonate injection should not be used as a solvent (see "Incompatibility").

All vials 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		Required amount of diluent (ml)	Approximate concentration (mg/ml)
1 g	Intramuscular Intravenous bolus Intravenous infusion	3 10 50*	260 90 20
2 g	Intravenous bolus Intravenous infusion	10 50*	170 40

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

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

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

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

The stability of both drugs 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 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 IU/mL or 50 IU/mL in 0.9% sodium chloride injection; potassium chloride 10 mEq/L 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 stopper of the vial 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 plunger fully depressed, insert the needle into the vial. Draw 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 g and 2 g vials) in two steps.

1. Insert the needle of the syringe through the stopper of the vial 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 air vent needle through the stopper until the drug is completely dissolved. Insert the air vent needle through the stopper into the vial to relieve internal pressure.
4. Add the resulting solution to an intravenous infusion system to achieve a total solution volume of at least 50 mL, and administer via intravenous infusion over 15–30 minutes.

Note. To ensure sterility of the product, it is essential not to insert the air vent needle through the stopper before 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, 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 not be stored for longer than 24 hours at a temperature of 2 to 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, 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 not be stored for longer than 24 hours at a temperature of 2 to 8°C.

Children.

Can be administered to 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 "Administration and Dosage" and "Special Warnings and 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 and < 1/10; uncommon ≥ 1/1000 and < 1/100; rare ≥ 1/10000 and < 1/1000; very rare < 1/10000; frequency not known.

Infections and infestations

Uncommon – candidiasis (including vaginal vaginitis and aphthous 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.

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 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 increase in blood urea levels.

Very rare – interstitial nephritis, acute renal failure.

Hepatobiliary disorders

Common – transient increase in 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 – angioneurotic edema, 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 – as with some other cephalosporins, transient increases in blood urea, blood urea nitrogen, and/or serum creatinine have occasionally been observed.

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

Reporting of adverse reactions after drug registration is highly important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy of the medicinal product to the State Expert Center of the Ministry of Health of Ukraine via the following link: https://aisf.dec.gov.ua.

Shelf life

3 years.

Storage conditions

Store in the original packaging, in a place inaccessible to children, at a temperature not exceeding 25°C.

Incompatibilities

Ceftazidime is less stable in solutions of sodium bicarbonate for injection than in other intravenous solutions; therefore, sodium bicarbonate is not recommended as a solvent.

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

Precipitation has been observed when vancomycin was added to ceftazidime solution; therefore, infusion systems and intravenous catheters should be flushed between administration of these two drugs.

Packaging 1 or 10 vials of powder in a cardboard box.

Prescription status Prescription only.

Manufacturer NSPC Hebei Huamin Pharmaceutical Company Limited.

Manufacturer's address and location of operations
No. 98 Huan Road, Economic and Technological Development Zone, Shijiazhuang, CN 052165, China.