INSTRUCTION

for medical use of the medicinal product

 

FLORAZIDE

 

Composition:

active substance: ceftazidime;

1 vial contains ceftazidime (as ceftazidime pentahydrate) 1 g or 2 g;

excipient: sodium carbonate.

 

Pharmaceutical form. Powder for solution for injection.

Basic physical and chemical properties: white to pale yellow powder.

 

Pharmacotherapeutic group. Antibacterial agent for systemic use. Third-generation cephalosporins. ATC code J01DD02.

 

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Ceftazidime inhibits bacterial cell wall synthesis by interacting with penicillin-binding proteins (PBPs). This leads to disruption of cell wall (peptidoglycan) biosynthesis, resulting in lysis and death of bacterial cells.

PK/PD relationship

For cephalosporins, the most important pharmacokinetic-pharmacodynamic (PK-PD) index correlating with in vivo efficacy is the percentage of the dosing interval during which the unbound concentration remains above the minimum inhibitory concentration (MIC) of ceftazidime for the target species (i.e., % T > MIC).

Mechanism of resistance

Bacterial resistance to ceftazidime may be due to one or more of the following mechanisms:

Hydrolysis by beta-lactamases. Ceftazidime may be effectively hydrolyzed by extended-spectrum beta-lactamases (ESBLs), including the SHV family of ESBLs and AmpC enzymes, which may be induced or stably depressed in some aerobic Gram-negative bacteria; Reduced affinity of penicillin-binding proteins for ceftazidime; Outer membrane impermeability, which restricts access of ceftazidime to penicillin-binding proteins in Gram-negative organisms; Bacterial efflux pumps.

 

Susceptibility breakpoints

Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

Bacteria	Breakpoints (mg/L)
	S	I	R
Enterobacteriaceae	≤ 1	2–4	> 4
Pseudomonas aeruginosa	≤ 81	–	> 8
Non-species related breakpoints2	≤ 4	8	> 8

S – susceptible, I – intermediate, R – resistant.

¹ Breakpoints relate to high dose therapy (2 g × 3).

² Non-species related breakpoints have been determined mainly based on PK/PD data and are independent of MIC distributions of specific bacterial species. They are intended for use only for species not mentioned in the table.

 

Microbiological susceptibility

The prevalence of acquired resistance may vary geographically and with time, therefore local information on resistance is desirable, particularly when treating severe infections. If necessary, expert advice should be sought when local resistance prevalence is such that the benefit of the medicinal product, at least for some types of infections, is questionable.

 

Susceptible species

Gram-positive aerobes

Streptococcus pyogenes
Streptococcus agalactiae

Gram-negative aerobes

Citrobacter koseri
Haemophilus influenzae
Moraxella catarrhalis
Neisseria meningitidis
Pasteurella multocida
Proteus mirabilis
Proteus spp. (others)
Providencia spp.

Species for which resistance may be an issue

Gram-negative aerobes

Acinetobacter baumannii⁺
Burkholderia cepacia
Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Klebsiella pneumoniae
Klebsiella spp. (others)
Pseudomonas aeruginosa
Serratia spp.
Morganella morganii

Gram-positive aerobes

Staphylococcus aureus*
Streptococcus pneumoniae**
Viridans group streptococcus

Gram-positive anaerobes

Clostridium perfringens
Peptostreptococcus spp.

Gram-negative anaerobes

Fusobacterium spp.

Resistant microorganisms

Gram-positive aerobes

Enterococcus spp., including Enterococcus faecalis and Enterococcus faecium
Listeria spp.

Gram-positive anaerobes

Clostridium difficile

Gram-negative anaerobes

Bacteroides spp. (most strains of Bacteroides fragilis are resistant)

Others

Chlamydia spp.
Mycoplasma spp.
Legionella spp.

* Methicillin-susceptible Staphylococcus aureus has weak species resistance to ceftazidime. All methicillin-resistant S. aureus are resistant to ceftazidime.

** Streptococcus pneumoniae that are intermediate or resistant to penicillin can be expected to have at least reduced susceptibility to ceftazidime.

+ High rates of resistance have been observed in one or more areas/countries/regions within the EU.

Pharmacokinetics.

Absorption

In patients, after intramuscular injection of ceftazidime 500 mg and 1 g, mean peak concentrations of 18 and 37 mg/L, respectively, are achieved rapidly. Five minutes after intravenous bolus injection of 500 mg, 1 g, or 2 g, mean serum concentrations of 46, 87, and 170 mg/L, respectively, are achieved. The kinetics of ceftazidime are linear within a single dose of 0.5–2 g after intravenous or intramuscular administration.

Distribution

Plasma protein binding is approximately 10%. Concentrations of ceftazidime exceeding the minimum inhibitory concentration (MIC) for most common pathogenic microorganisms are achieved in tissues and fluids such as bone, heart, bile, sputum, intraocular, synovial, pleural, and peritoneal fluids. Ceftazidime rapidly crosses the placenta and is excreted into breast milk. The drug poorly crosses the intact blood-brain barrier; in the absence of inflammation, the concentration of the drug in the central nervous system is low. However, during meningeal inflammation, the concentration of ceftazidime in the central nervous system is 4–20 mg/L or higher, which corresponds to its therapeutic concentration level.

Biotransformation

Ceftazidime is not metabolized in the body.

Elimination

After parenteral administration, plasma levels decline with a half-life of about 2 hours. Ceftazidime is excreted unchanged in active form in the urine by glomerular filtration; approximately 80–90% of the dose is excreted in the urine within 24 hours. Less than 1% of the drug is excreted in bile.

Special patient groups

Renal impairment

In patients with impaired renal function, ceftazidime elimination is reduced; therefore the dose should be reduced (see section "Method of administration and dosage").

Hepatic impairment

The presence of mild and moderate hepatic dysfunction did not affect the pharmacokinetics of ceftazidime in patients administered the drug at a dose of 2 g intravenously every 8 hours for 5 days, provided renal function was not impaired (see section "Method of administration and dosage").

Elderly patients

The decreased clearance observed in elderly patients was mainly due to age-related decline in renal clearance of ceftazidime. The mean half-life of the drug in elderly patients (aged 80 years) is 3.5–4 hours after both single and prolonged (for 7 days) administration at a dose of 2 g twice daily intravenously (bolus).

Children

The half-life of ceftazidime is prolonged in premature and full-term neonates from 4.5 to 7.5 hours after administration of a dose of 25–30 mg/kg. However, in patients aged 2 months and older, the half-life is within the adult range.

 

Clinical characteristics.

Indications.

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

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

Treatment of bacteraemia that occurs in patients as a result of any of the above infections.

Ceftazidime may be used to treat patients with neutropenia and fever that occurs as a result of bacterial infection.

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

When prescribing ceftazidime, its antibacterial spectrum, directed mainly against Gram-negative aerobes, should be considered (see sections "Precautions for use" and "Pharmacological properties").

Ceftazidime should be used with other antibacterial agents if the range of microorganisms causing the infection is expected not to fall within the spectrum of ceftazidime.

The drug should be prescribed according to existing official guidelines for the use of antibacterial agents.

 

Contraindications.

Hypersensitivity to ceftazidime or to other components of the drug.

Hypersensitivity to cephalosporin antibiotics.

History of severe hypersensitivity (e.g., anaphylactic reactions) to other beta-lactam antibiotics (penicillins, monobactams, and carbapenems).

 

Interaction with other medicinal products and other forms of interaction.

Concomitant use of high doses of the drug with nephrotoxic medicinal products may adversely affect renal function (see section "Precautions for use").

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

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

Ceftazidime does not affect the results of glucosuria determination by enzymatic methods, but a slight effect on test results may be observed when using copper reduction methods (Benedict's, Fehling's, Clinitest).

Ceftazidime does not affect the alkaline picrate method for creatinine determination.

 

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, treatment with ceftazidime should be discontinued immediately and appropriate emergency measures taken.

Before starting treatment, it should be determined whether the patient has a history of severe hypersensitivity reactions to ceftazidime, cephalosporin antibiotics, or other beta-lactam antibiotics. The drug should be prescribed with caution to patients who have had non-severe hypersensitivity reactions to other beta-lactam antibiotics.

Severe cutaneous adverse reactions (SCARs)

With a frequency of "unknown", severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with ceftazidime treatment.

Patients should be informed of the signs and symptoms and carefully monitored for skin reactions.

If signs and symptoms indicating these reactions appear, ceftazidime should be discontinued immediately and alternative treatment considered.

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

Spectrum of activity

Ceftazidime has a limited spectrum of antibacterial activity. It is not suitable for use as monotherapy for some types of infections unless the pathogen and its susceptibility to this drug are known, or there is a high probability that the likely pathogen will be susceptible to ceftazidime treatment. This is particularly important when considering treatment of patients with bacteraemia, bacterial meningitis, skin and soft tissue infections, and bone and joint infections. Furthermore, ceftazidime is susceptible to hydrolysis by some extended-spectrum beta-lactamases. Therefore, when choosing ceftazidime for treatment, information on the prevalence of microorganisms producing extended-spectrum beta-lactamases should be considered.

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

Pseudomembranous colitis

Cases of pseudomembranous colitis, ranging from mild to life-threatening, have been reported with antibiotic use. This should be considered when diagnosing patients who develop diarrhea during or after antibiotic use. In case of prolonged and significant diarrhea or the occurrence of abdominal cramps, treatment should be discontinued immediately, the patient should be further evaluated, and if necessary, specific treatment for Clostridium difficile should be prescribed. Drugs that slow intestinal peristalsis should not be prescribed.

Renal function

Concomitant treatment with high doses of cephalosporins and nephrotoxic drugs such as aminoglycosides or potent diuretics (e.g., furosemide) may adversely affect renal function. Ceftazidime is excreted by the kidneys, therefore the dose should be reduced according to the degree of renal impairment. Careful clinical monitoring of the safety and efficacy of the drug is recommended for patients with renal impairment. Cases of neurological complications have been reported when the dose was not appropriately reduced (see sections "Method of administration and dosage" and "Adverse reactions").

Overgrowth of non-susceptible microorganisms

As with other broad-spectrum antibiotics, prolonged treatment with ceftazidime may lead to overgrowth of non-susceptible microorganisms (e.g., Candida, Enterococci); in this case, discontinuation of treatment or taking other necessary measures may be required. Continuous monitoring of the patient's condition is very important.

Effect on laboratory parameters

Ceftazidime does not affect the results of enzymatic methods for glucosuria determination, but may slightly affect results when using copper reduction techniques (Benedict's, Fehling's, "Clinitest"): false-positive results may be obtained.

Ceftazidime does not affect the result of creatinine level testing using alkaline picrate.

Approximately 5% of patients receiving ceftazidime had a positive Coombs test. This phenomenon may interfere with blood cross-matching tests.

Sodium content

The medicinal product contains sodium (1 vial with 1 g ceftazidime – 52 mg (2.3 mmol) of sodium), which should be considered when treating patients on a controlled sodium diet.

 

Pregnancy and lactation.

Pregnancy

Data on treatment with ceftazidime in pregnant women are limited. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/fetal development, parturition, or postnatal development. The drug should be prescribed to pregnant women only when the benefit of its use outweighs the possible risk.

Breastfeeding

Ceftazidime is excreted into breast milk in small amounts, but at therapeutic doses, no effect on breastfed infants is expected. Ceftazidime may be used during breastfeeding.

Fertility

No data are available.

 

Effects on ability to drive and use machines.

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

 

Method of administration and dosage.

Adults and children with body weight ≥ 40 kg

Table 1

Intermittent administration
Infection	Dose to be administered
Respiratory tract infections in patients with cystic fibrosis	100–150 mg/kg body weight/day every 8 hours, maximum up to 9 g per day1
Febrile neutropenia Hospital-acquired pneumonia Bacterial meningitis Bacteraemia*	2 g every 8 hours
Bone and joint infections Complicated skin and soft tissue infections Complicated intra-abdominal infections Peritonitis associated with continuous ambulatory peritoneal dialysis	1–2 g every 8 hours
Complicated urinary tract infections	1–2 g every 8 or 12 hours
Prophylaxis of infectious complications during prostate surgery (transurethral resection)	1 g at anaesthesia induction, 1 g at catheter removal
Chronic otitis media Malignant otitis externa	1–2 g every 8 hours

 

Continuous infusion
Infection	Dose to be administered
Febrile neutropenia 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 Peritonitis associated with continuous ambulatory peritoneal dialysis	Administer a loading dose of 2 g followed by continuous infusion of 4 to 6 g every 24 hours1

¹ In adult patients with normal renal function, the use of 9 g per day did not lead to adverse reactions.

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

 

Children with body weight < 40 kg

Table 2

Infants and children aged > 2 months and with body weight < 40 kg	Infection	General dose
Intermittent administration
	Complicated urinary tract infections	100–150 mg/kg body weight/day in 3 divided doses, maximum 6 g per day
	Chronic otitis media
	Malignant otitis externa
	Neutropenia in children	150 mg/kg body weight/day 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/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	Administer a loading dose of 60–100 mg/kg body weight followed by continuous infusion of 100–200 mg/kg body weight per day, maximum up to 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
	Peritonitis associated with continuous ambulatory peritoneal dialysis
Infants and children aged ≤ 2 months	Infection	General dose
Intermittent administration
	Most infections	25–60 mg/kg body weight/day in 2 divided doses1

¹ In infants and children aged ≤ 2 months, the serum half-life may be 2–3 times longer than in adults.

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

 

Children

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

Elderly patients

Considering the decreased clearance of ceftazidime, for elderly patients with acute infections, the daily dose should generally not exceed 3 g, especially for patients aged 80 years and older.

Hepatic impairment

No dose adjustment is necessary for patients with mild and moderate hepatic impairment. No clinical studies have been conducted in patients with severe hepatic impairment. Careful clinical monitoring of efficacy and safety is recommended.

Renal impairment

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

The initial dose should be 1 g. Determination of 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 increased accordingly. Serum ceftazidime levels should be monitored in such patients.

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 and may not accurately reflect the level of renal function reduction in all patients with renal impairment.

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

Careful clinical monitoring of efficacy and safety 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 interval, hours
50–31	150–200 (1.7–2.3)	Administer a loading dose of 2 g followed by continuous infusion of 1 to 3 g every 24 hours
30–16	200–350 (2.3–4)	Administer a loading dose of 2 g followed by continuous infusion of 1 g every 24 hours
≤ 15	> 350 (4–5.6)	Not studied

Dose selection should be done with caution. Careful clinical monitoring of efficacy and safety is recommended.

Children with body weight < 40 kg

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

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

Haemodialysis

The serum half-life of ceftazidime during haemodialysis ranges from 3 to 5 hours.

After each haemodialysis session, a maintenance dose of ceftazidime as recommended in Tables 6 and 7 below should be administered.

Peritoneal dialysis

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

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

For patients with renal failure undergoing prolonged arteriovenous haemodialysis or high-flux hemofiltration in intensive care units, the recommended dose is 1 g per day as a single dose or in divided doses. For low-flux hemofiltration, doses as for renal impairment should be used.

For patients undergoing venovenous hemofiltration and venovenous haemodialysis, dosage recommendations are provided in Tables 6 and 7.

 

Dosage 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

^a The maintenance dose should be administered every 12 hours.

 

Dosage recommendations for ceftazidime in patients undergoing prolonged venovenous haemodialysis

Table 7

Residual renal function (creatinine clearance, ml/min)	Maintenance dose (mg) for dialysate at flow rate (ml/min)а
	1 L/hour			2 L/hour
	Ultrafiltration rate (L/hour)			Ultrafiltration rate (L/hour)
	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

^a The maintenance dose should be administered every 12 hours.

Administration.

Ceftazidime is administered intravenously by injection or infusion, or by deep intramuscular injection. Recommended sites for intramuscular injection are the upper outer quadrant of the gluteus maximus muscle or the lateral aspect of the thigh.

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

The dose depends on the severity of the disease, susceptibility, location and type of infection, as well as the age and renal function of the patient.

Instructions for solution preparation

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

Vials of all sizes are manufactured under reduced pressure. As the drug dissolves, carbon dioxide is released and the pressure in the vial increases. Small bubbles of carbon dioxide in the dissolved drug can be ignored.

Table 8

Dose and method of administration		Required volume of solvent (ml)	Approximate concentration (mg/ml)
1 g	Intramuscular	3	260
	Intravenous bolus	10	90
	Intravenous infusion	50*	20
2 g	Intravenous bolus	10	170
	Intravenous infusion	50*	40

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

The colour of the solution ranges from pale yellow to amber depending on concentration, solvent, and storage conditions. When following recommendations, the action of the drug does not depend on variations in its colour.

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 intraperitoneal dialysis fluid (lactate).

Ceftazidime for intramuscular administration may be dissolved in 0.5% or 1% lidocaine hydrochloride solution.

The efficacy of both drugs is maintained when ceftazidime at a dose 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 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.

The contents of a Florazide 1 g vial, dissolved in 1.5 ml of water for injections, can be added to a metronidazole solution (500 mg in 100 ml), with both drugs retaining their activity.

Preparation of solutions for intramuscular or intravenous bolus injection

Insert the syringe needle through the vial stopper and inject the recommended volume of solvent. Remove the syringe needle and shake the vial until a clear solution is obtained. Invert the vial. With the syringe plunger fully depressed, insert the needle into the vial. Draw the entire solution into the syringe, keeping the needle in the solution at all times. Small bubbles of carbon dioxide can be ignored.

Preparation of solutions for intravenous infusion (1 g and 2 g vials) in 2 stages

Insert the syringe needle through the vial stopper and inject 10 ml of solvent. Remove the syringe needle and shake the vial until a clear solution is obtained. Do not insert the air needle until the drug is completely dissolved. Insert the air needle through the stopper into the vial to relieve internal pressure in the vial. Add the resulting solution to the intravenous infusion system, creating a total solution volume of at least 50 ml, and use for intravenous infusion over 15–30 minutes.

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

After reconstitution

After reconstitution, the medicinal product maintains chemical and physical stability for 8 hours at 25 °C.

From a microbiological point of view, the solution should be used immediately. If not used immediately, the user is responsible for the duration and conditions of storage of the solution until use. If reconstitution has not taken place in controlled and validated aseptic conditions, the solution should be stored for no 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 8 hours at 25 °C.

From a microbiological point of view, the solution should be used immediately after reconstitution and dilution. If not used immediately, the user is responsible for the duration and conditions of storage of the solution until use. If reconstitution has not taken place in controlled and validated aseptic conditions, the solution should be stored for no longer than 24 hours at a temperature of 2 to 8 °C.

 

Children.

Use 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 insufficiency if the dose is not appropriately reduced (see sections "Method of administration and dosage" and "Precautions for use"). The serum concentration of ceftazidime can be reduced by haemodialysis or peritoneal dialysis.

 

Adverse reactions.

The most common adverse reactions are eosinophilia, thrombocytosis, phlebitis or thrombophlebitis with intravenous administration, diarrhea, transient elevation of liver enzymes, maculopapular rash or urticaria, pain and/or inflammation after intramuscular injection, positive Coombs test.

Within each frequency group, adverse reactions are presented in order of decreasing seriousness.

Adverse effects have been classified by frequency of occurrence – from very common to uncommon, and by system organ class: very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1000 and < 1/100; rare ≥ 1/10000 and < 1/1000; very rare < 1/10000; frequency unknown.

Infections and infestations
Uncommon – candidiasis (including vaginitis and oral candidiasis).

Blood and lymphatic system disorders
Common – eosinophilia and thrombocytosis.
Uncommon – leukopenia, neutropenia, and thrombocytopenia.
Not known – lymphocytosis, haemolytic anaemia, and agranulocytosis.

Immune system disorders
Not known – anaphylaxis (including bronchospasm and/or arterial hypotension) (see section "Precautions for use").

Nervous system disorders
Uncommon – dizziness, headache.
Not known – neurological complications¹, paraesthesia.
Neurological complications such as tremor, myoclonus, seizures, encephalopathy, and coma have been reported in patients with renal insufficiency for whom the dose of ceftazidime was not appropriately reduced.

Vascular disorders
Common – phlebitis or thrombophlebitis at the injection site.

Gastrointestinal disorders
Common – diarrhea.
Uncommon – antibiotic-associated diarrhea and colitis² (see section "Precautions for use"), abdominal pain, nausea, vomiting.
Not known – taste disturbance.

Hepatobiliary disorders
Common – transient elevation of one or more liver enzymes³.
Not known – jaundice.

Skin and subcutaneous tissue disorders
Common – maculopapular rash or urticaria.
Uncommon – pruritus.
Not known – toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)⁴, acute generalized exanthematous pustulosis (AGEP).

Renal and urinary disorders
Uncommon – transient elevation of blood urea, blood urea nitrogen, and/or serum creatinine.
Very rare – interstitial nephritis, acute renal failure.

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

Laboratory parameters
Common – positive Coombs test⁵.

¹   Neurological complications such as tremor, myoclonus, seizures, encephalopathy, and coma have been reported in patients with renal insufficiency for whom the dose of ceftazidime was not appropriately reduced.

² Diarrhea and colitis may be associated with Clostridium difficile and may manifest as pseudomembranous colitis.

³   Alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP).

⁴   There have been rare reports of DRESS syndrome associated with ceftazidime.

⁵   A positive Coombs test occurs in approximately 5% of patients, which may interfere with blood cross-matching tests.

 

Adverse Reactions Reporting

Adverse reactions reporting after the registration of a medicinal product is of great importance. It enables the monitoring of the benefit/risk ratio associated with the use of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives, should report all suspected adverse reactions and cases of lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

 

Shelf life.

Florazide, powder for solution for injection 1 g – 3 years.

Florazide, powder for solution for injection 2 g – 2 years.

 

Storage conditions.

Store in the original package at a temperature not exceeding 25 °C. Keep out of reach of children. The prepared solution can be stored for not more than 8 hours at a temperature not exceeding 25 °C and for not more than 24 hours at a temperature of 2 to 8 °C.

 

Incompatibility.

Ceftazidime is less stable in sodium bicarbonate injection solution than in other intravenous solutions, therefore it 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, it is recommended to flush infusion systems and intravenous catheters between the use of these two drugs.

 

Packaging. Powder in a glass vial closed with a rubber stopper and aluminum cap with a flip-off component, one vial per box.

 

Terms of dispensing.

On prescription.

 

Date of last update.

13.08.2026