Fortum

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FORTUM® (FORTUM®)

Composition:

Active substance: ceftazidime;

1 vial contains ceftazidime (as ceftazidime pentahydrate) 500 mg or 1 g or 2 g;

Excipient: anhydrous sodium carbonate.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical characteristics: white to cream-colored powder.

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 across different regions and may change over time, with significant differences possible among individual strains. It is advisable to use local (regional) data on antibiotic susceptibility and 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 streptococci.

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 concentrations of 18 and 37 mg/L are rapidly achieved, respectively. 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 are achieved, respectively. Therapeutically effective concentrations persist in serum for up to 8–12 hours after intravenous or intramuscular administration. Plasma protein binding is approximately 10%. Therapeutic concentrations exceeding the MIC for most common pathogenic microorganisms are achieved in tissues and 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 poorly penetrates the intact blood-brain barrier; in the absence of inflammation, CNS concentrations are low. However, during meningitis, ceftazidime concentrations in the CNS range from 4 to 20 mg/L or higher, achieving therapeutic levels.

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

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-mentioned 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 prostate surgery (transurethral resection).

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

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

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

Contraindications.

Hypersensitivity to ceftazidime or to any of the excipients 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 administration 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 Fortum with chloramphenicol is proposed, the possibility of antagonism should be considered.

Like other antibiotics, Fortum 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 glucose in urine testing; however, a minor interference in test results may occur when using copper reduction methods (Benedict, Fehling, Clinitest).

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

Special precautions for use

As with other beta-lactam antibiotics, severe and occasionally 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 cephalosporins, or other beta-lactam antibiotics. Caution is advised when prescribing ceftazidime to patients with a history of non-severe hypersensitivity reactions to other beta-lactam antibiotics.

Ceftazidime has a limited antibacterial spectrum. It is not an appropriate agent for monotherapy of certain types of infections unless the causative organism is known to be susceptible to ceftazidime or there is a high likelihood that the likely 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. Additionally, ceftazidime is susceptible to hydrolysis by certain extended-spectrum beta-lactamases. Therefore, when selecting ceftazidime for treatment, information regarding the prevalence of microorganisms producing extended-spectrum beta-lactamases should be taken into account.

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, dosage adjustment is required 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 "Side effects").

As with other broad-spectrum antibiotics, prolonged treatment with Fortum 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 and continuous monitoring of the patient is essential.

Cases of pseudomembranous colitis, ranging from mild to life-threatening in severity, 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 and severe diarrhea occurs, or if abdominal cramps develop, treatment should be discontinued immediately, further diagnostic evaluation performed, and specific therapy for Clostridium difficile initiated if necessary. Antiperistaltic agents 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.

Fortum contains sodium (one vial of 500 mg ceftazidime contains 26 mg (1.15 mmol) sodium; one vial of 1 g ceftazidime contains 52 mg (2.3 mmol) sodium; one vial of 2 g ceftazidime contains 104 mg (4.6 mmol) sodium), which should be taken into account when treating patients on a sodium-restricted diet.

Serious skin reactions (SSRs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported during ceftazidime therapy. These reactions may be life-threatening or fatal and occur with an "unknown" frequency.

Patients should be informed about the signs and symptoms of these 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 considered.

If a serious reaction such as SJS, TEN, DRESS, or AGEP develops during ceftazidime therapy, ceftazidime must never be restarted.

Use during pregnancy or breastfeeding

Data on ceftazidime use in pregnant women are limited. Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonal or fetal development, or postnatal development. Ceftazidime should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Ceftazidime is excreted in breast milk in small amounts, but effects on the breastfed infant are not 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, certain adverse reactions (e.g., dizziness) may occur, which could impair the ability to drive or operate machinery (see section "Side effects").

Method of administration and dosage.

Table 1

Adults and children with body weight ≥ 40 kg

Intermittent administration
Infection	Dose administered
respiratory tract infections in patients with cystic fibrosis	100–150 mg/kg body weight/day every 8 hours, up to a maximum of 9 g per day1
febrile neutropenia	2 g every 8 hours
hospital-acquired pneumonia
bacterial meningitis
bacteremia*
bone and joint infections	1–2 g every 8 hours
complicated skin and soft tissue infections
complicated intra-abdominal infections
peritonitis associated with continuous ambulatory peritoneal dialysis
complicated urinary tract infections	1–2 g every 8 or 12 hours
prophylaxis of infectious complications during surgery on the prostate gland (transurethral resection)	1 g at the time of induction of anesthesia, and a second dose 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 9 g per day did not result in adverse reactions.

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

Table 2

Children < 40 kg

Infants and children older than 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 and children aged ≤ 2 months	Infection	Usual dose
Intermittent administration
	Most infections	25–60 mg/kg body weight/day in 2 divided doses1
1In infants and children aged ≤ 2 months, the serum half-life may be 2–3 times longer than in adults

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

Children

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

Geriatric patients

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

Hepatic impairment

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

Table 3

Adults and children with body weight ≥ 40 kg body weight

Creatinine clearance, mL/min	Approximate serum creatinine level, µmol/L (mg/dL)	Recommended single dose of ceftazidime, g	Dosing frequency, 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 serum ceftazidime levels is recommended.

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

Table 4

Children with body weight < 40 kg

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

* Serum creatinine level calculated according to recommendations, which may not precisely 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 use is recommended.

Recommended maintenance doses of ceftazidime in renal insufficiency – continuous infusion

Table 5

Adults and children with body weight ≥ 40 kg

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 Fortum 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 continuous intravenous infusion of the drug 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 serum half-life of ceftazidime during hemodialysis ranges from 3 to 5 hours.

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

Peritoneal dialysis

Ceftazidime can be used during peritoneal dialysis, including continuous ambulatory peritoneal dialysis (CAPD).

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 hemofiltration 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 the same as those recommended for impaired renal function.

Dosage recommendations for patients undergoing venovenous hemofiltration and venovenous hemodialysis are provided in tables 6–7.

Table 6

Dosage recommendations for ceftazidime in patients undergoing prolonged venovenous hemofiltration

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

The maintenance dose should be administered every 12 hours.

Table 7

Dosing recommendations for ceftazidime in patients undergoing prolonged venovenous hemodialysis

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

Fortum should be administered by intravenous injection or infusion or by deep intramuscular injection. Recommended sites for intramuscular administration are the upper outer quadrant of the gluteus maximus 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 dose depends on the severity of the infection, the susceptibility, location, and type of infection, as well as on the patient's age and renal function.

Instructions for solution preparation

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

All vials are manufactured under reduced pressure. As the drug dissolves, carbon dioxide is released and pressure inside the vial increases. 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)
250 mg	Intramuscular Intravenous bolus	1 2.5	210 90
500 mg	Intramuscular Intravenous bolus	1.5 5	260 90
1 g	Intramuscular Intravenous bolus Intravenous infusion	3 10 50*	260 90 20
2 g	Intravenous bolus Intravenous infusion	10 50*	170 40

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

The color of the solution may vary from light yellow to amber depending on concentration, diluent, and storage conditions. Provided the recommended procedures are followed, the activity of the drug is not affected by variations in its color.

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).

Ceftazidime for intramuscular administration 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 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 500 mg Fortum vial reconstituted with 1.5 mL of water for injection may be added to a metronidazole solution (500 mg in 100 mL), and both drugs retain their activity.

Preparation of solutions 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, keeping the needle tip submerged in the solution at all times. Small bubbles of carbon dioxide may be disregarded.

Preparation of solutions for intravenous infusion (1 g and 2 g vials) in two steps:

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 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 6 days at 4 °C and for 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 be stored for no more than 24 hours at a temperature of 2 to 8 °C.

After dilution:

After dilution, the medicinal product maintains chemical and physical stability for 6 days at 4 °C and for 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 be stored for no more than 24 hours at a temperature of 2 to 8 °C.

Children.

May 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 "Method of administration and dosage" and "Special instructions"). Serum concentrations of ceftazidime can be reduced by hemodialysis or peritoneal dialysis.

Adverse Reactions

Adverse effects have been classified according to their frequency of occurrence – from very common to uncommon – and by organ systems: very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1000 and < 1/100; rare ≥ 1/10000 and < 1/1000; very rare < 1/10000; frequency not known.

Infections and infestations

Uncommon – candidiasis (including vaginitis and candidal stomatitis).

Blood and lymphatic system

Common – eosinophilia and thrombocytosis.

Uncommon – leukopenia, neutropenia, and thrombocytopenia.

Frequency not known – lymphocytosis, hemolytic anemia, agranulocytosis.

Immune system

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

Nervous system

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 appropriately reduced doses 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 manifest as pseudomembranous colitis (see section "Special precautions").

Frequency not known – taste disturbances.

Renal and urinary system

Uncommon – transient increase in blood urea levels.

Very rare – interstitial nephritis, acute renal failure.

Hepatobiliary reactions

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

Frequency not known – jaundice.

Skin and subcutaneous tissue

Common – maculopapular rash or urticaria.

Uncommon – pruritus.

Frequency not known – angioneurotic edema, polymorphic erythema, acute generalized exanthematous pustulosis (AGEP), Stevens–Johnson syndrome, and toxic epidermal necrolysis.

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 elevations 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.

Shelf life.

3 years.

Storage conditions.

Store the vial with lyophilized powder below 25°C in a place protected from light. Keep out of reach of children.

Incompatibilities.

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

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

Cases of precipitate formation have been observed when vancomycin was added to ceftazidime solution. Therefore, it is recommended to flush infusion systems and intravenous catheters between administration of these two drugs.

Packaging. Glass vial with a bromobutyl rubber stopper and aluminum seal, covered with a cap, placed in a cardboard package.

Prescription status. Prescription only.

Manufacturer.

A.C.S. Dobfar S.p.A., Italy / ACS Dobfar S.r.L., Italy

Manufacturer's address and place of business.

Via Alessandro Fleming, 2, Verona, 37135, Italy / Via Alessandro Fleming, 2, Verona, 37135, Italy