Fortum (Powder) Instructions for Use

Marketing Authorization Holder

Sandoz, d.d. (Slovenia)

Manufactured By

ACS Dobfar, S.p.A. (Italy)

ATC Code

J01DD02 (Ceftazidime)

Active Substance

Ceftazidime (Rec.INN registered by WHO)

Dosage Forms

	Fortum	Powder for preparation of solution for injections 1 g: vial 1 pc.
		Powder for preparation of solution for injections 2 g: vial 1 pc.
		Powder for preparation of solution for injections 250 mg: vial 1 pc.
		Powder for preparation of solution for injections 500 mg: vial 1 pc.

Dosage Form, Packaging, and Composition

Powder for preparation of solution for injections from white to light yellow color.

Excipients: sodium carbonate (anhydrous), carbon dioxide.

Vials (1) – cardboard packs.

Clinical-Pharmacological Group

Third generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Cephalosporin antibiotic of the third generation. It has a bactericidal effect by disrupting the synthesis of the microbial cell wall. It has a broad spectrum of antimicrobial activity (including strains of pathogens resistant to gentamicin and other aminoglycoside antibiotics). It is resistant to the action of most beta-lactamases.

In vitro studies have shown that Ceftazidime is active against gram-negative bacteria Pseudomonas aeruginosa, Pseudomonas spp. (including Pseudomonas pseudomallei), Klebsiella spp. (including Klebsiella pneumoniae), Proteus mirabilis, Proteus vulgaris, Morganella morganii, Proteus rettgeri, Providencia spp., Escherichia coli, Enterobacter spp., Citrobacter spp., Serratia spp., Salmonella spp., Shigella spp., Yersinia enterocolitica, Pasteurella multocida, Acinetobacter spp., Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae (including strains resistant to ampicillin), Haemophilus parainfluenzae (including strains resistant to ampicillin); gram-positive bacteria Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Micrococcus spp., Streptococcus pyogenes (beta-hemolytic streptococcus group A), Streptococcus group B (Streptococcus agalactiae), Streptococcus pneumoniae, Streptococcus mitis, Streptococcus spp. (excluding Streptococcus faecalis); anaerobic bacteria Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Clostridium perfringens, Fusobacterium spp., Bacteroides spp. (many strains of Bacteroides fragilis are resistant).

Ceftazidime is not active against methicillin-resistant staphylococci, Streptococcus faecalis and many other Enterococcus spp., Listeria monocytogenes, Campylobacter spp., Clostridium difficile.

Pharmacokinetics

Absorption

After intramuscular administration of the drug in doses of 500 mg and 1 g, C_max in blood plasma is reached quickly and is 18 mg/l and 37 mg/l, respectively. Five minutes after intravenous bolus administration of the drug in doses of 500 mg, 1 g, or 2 g, plasma concentrations of ceftazidime are 46 mg/l, 87 mg/l, and 170 mg/l, respectively.

Distribution

After intravenous or intramuscular administration, therapeutic concentrations of the active substance in blood plasma persist for 8-12 hours. Plasma protein binding is 10%.

Ceftazidime concentrations exceeding the MIC for most common pathogenic microorganisms can be achieved in bone tissue, heart tissue, bile, sputum, synovial fluid, intraocular fluid, pleural and peritoneal fluids. Ceftazidime easily crosses the placental barrier and is excreted in breast milk. In the absence of inflammation in the meninges, Ceftazidime poorly penetrates the blood-brain barrier; the concentration of the drug in the cerebrospinal fluid (CSF) is low. In meningitis, therapeutic concentrations of ceftazidime are achieved in the CSF, amounting to 4-20 mg/l and higher.

Metabolism

Ceftazidime is not metabolized in the body.

Excretion

T_1/2 is about 2 hours. Ceftazidime is excreted unchanged 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 the bile.

Pharmacokinetics in special clinical cases

In case of impaired renal function, the elimination rate of ceftazidime decreases.

During hemodialysis, T_1/2 is 3-5 hours.

In newborns, T_1/2 is 3-4 times longer than in adults.

Indications

• Severe infections, including nosocomial infections (septicemia, bacteremia, peritonitis, meningitis, infections in patients with reduced immunity, infected burns);
• Respiratory tract infections and infections in patients with cystic fibrosis;
• ENT infections;
• Urinary tract infections;
• Skin and soft tissue infections;
• Gastrointestinal tract, biliary tract, and abdominal infections;
• Bone and joint infections;
• Infections associated with dialysis.

Prevention of infectious complications during prostate surgery (transurethral resection).

ICD codes

Dosage Regimen

The dose is set individually, depending on the severity of the disease, location, type of pathogen and its sensitivity to the drug, the patient’s age and renal function.

The drug is administered intravenously or deeply intramuscularly into the upper outer quadrant of the gluteus maximus muscle or into the lateral part of the thigh. The ceftazidime solution can be administered directly into a vein or into the tube of an infusion system.

The maximum daily dose is 6 g.

Adults are prescribed 1-6 g/day intravenously or intramuscularly. The frequency of administration is 2-3 times/day.

In most cases, 1 g is administered every 8 hours or 2 g at 12-hour intervals.

In severe disease, especially in patients with reduced immunity, including patients with neutropenia, 2 g is prescribed every 8 or 12 hours or 3 g every 12 hours.

For urinary tract infections and mild infections, it is recommended to administer 500 mg or 1 g every 12 hours.

For the treatment of infectious complications in cystic fibrosis caused by Pseudomonas, 100-150 mg/kg/day is prescribed in 3 divided doses.

For prostate surgery, Fortum is prescribed at a dose of 1 g during induction anesthesia and the second dose is administered upon catheter removal.

For elderly patients, especially those over 80 years of age, Fortum is recommended to be prescribed at a dose not exceeding 3 g/day.

For children over 2 months the drug is prescribed at a dose of 30-100 mg/kg/day; frequency of administration is 2-3 times/day.

For children with reduced immunity, cystic fibrosis, or meningitis, up to 150 mg/kg/day (maximum 6 g/day) is prescribed in 3 divided doses.

For newborns and infants under 2 months of age the drug is prescribed at a dose of 25-60 mg/kg/day in 2 divided doses.

For patients with renal impairment, a dose reduction is required because Ceftazidime is excreted by the kidneys unchanged.

The initial dose is 1 g. The maintenance dose is selected depending on the glomerular filtration rate.

Maintenance doses of ceftazidime in renal failure are presented in the table.

*The solution is added in 2 steps.

Depending on the concentration, type of solvent, and storage conditions, the resulting Fortum solution may range in color from light yellow to dark yellow. If the drug dilution rules are followed, its effectiveness does not depend on the shade.

Ceftazidime at concentrations from 1 to 40 mg/ml is compatible with the following solutions: 0.9% sodium chloride solution; Hartmann’s solution; 5% dextrose solution; 0.225% sodium chloride and 5% dextrose solution; 0.45% sodium chloride and 5% dextrose solution; 0.9% sodium chloride and 5% dextrose solution; 0.18% sodium chloride and 4% dextrose solution; 10% dextrose solution; dextran 40 for injection 10% in 0.9% sodium chloride solution; dextran 40 for injection 10% in 5% dextrose solution; dextran 70 for injection 6% in 0.9% sodium chloride solution; dextran 70 for injection 6% in 5% dextrose solution.

At concentrations from 0.05 to 0.25 mg/ml, Ceftazidime is compatible with intraperitoneal dialysis solution (lactate).

For intramuscular administration, Ceftazidime can be diluted with 0.5% or 1% lidocaine hydrochloride solution.

If Ceftazidime at a concentration of 4 mg/ml is mixed with the following solutions, both components remain active: hydrocortisone (hydrocortisone sodium phosphate) 1 mg/ml in 0.9% sodium chloride solution or 5% dextrose solution; cloxacillin (cloxacillin sodium) 4 mg/ml in 0.9% sodium chloride solution; heparin 10 IU/ml or 50 IU/ml in 0.9% sodium chloride solution; potassium chloride 10 mEq/l or 40 mEq/l in 0.9% sodium chloride solution.

When mixing ceftazidime solution (500 mg in 1.5 ml water for injections) and metronidazole (500 mg/100 ml), both components retain their activity.

Preparation of solution for intramuscular or intravenous bolus administration

1. Insert the syringe needle into the vial through the rubber stopper and add the recommended amount of solvent through it.
2. Remove the syringe needle and shake the vial to obtain a clear solution.
3. Turn the vial over. With the syringe plunger fully inserted, pierce the vial’s rubber stopper with the needle and advance it into the vial so that it is completely in the solution. Draw all the solution into the syringe. The solution in the syringe may contain small bubbles of carbon dioxide.

Preparation of solution for intravenous infusion (vials containing 1 g or 2 g of the drug)

1. Insert the syringe needle into the vial through the rubber stopper and add 10 ml of solvent through it.
2. Remove the syringe needle and shake the vial to obtain a clear solution.
3. Insert a gas outlet needle into the vial cap to reduce internal pressure in the vial.
4. Without removing the gas outlet needle, add the remaining amount of solvent to the vial. Remove both needles (the gas outlet needle and the syringe needle) from the vial cap; shake the vial and set it up for infusion.

To ensure sterility, it is important not to insert the gas outlet needle into the vial until the powder has dissolved.

Adverse Reactions

From the digestive system diarrhea, nausea, vomiting, abdominal pain, oral and pharyngeal candidiasis, transient increase in ALT, AST, LDH, GGT, and ALP activity; very rarely – jaundice.

As with the use of other cephalosporins, colitis may be caused by Clostridium difficile and manifest as pseudomembranous colitis.

From the hematopoietic system eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, lymphocytosis, hemolytic anemia.

From the central and peripheral nervous system headache, dizziness, paresthesia, taste disturbance; more often in patients with renal failure – neurological disorders including tremor, myoclonus, convulsions, encephalopathy, coma.

From the urinary system transient increase in blood urea, urea nitrogen and/or creatinine levels, impaired renal function.

Allergic reactions maculopapular rash, urticaria, fever, itching, angioedema, bronchospasm, decreased blood pressure, exudative multiforme erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Local reactions phlebitis or thrombophlebitis with intravenous administration; pain, burning, induration at the injection site with intramuscular administration.

Other candidal vaginitis, false-positive direct Coombs test.

Contraindications

• Hypersensitivity to ceftazidime and other components of the drug;
• Hypersensitivity to other cephalosporin antibiotics, penicillins.

Use with caution in renal failure, gastrointestinal diseases (including history and ulcerative colitis), during pregnancy, during lactation, in newborns, in combination with “loop” diuretics and aminoglycosides.

Use in Pregnancy and Lactation

Fortum should be used with caution in the first months of pregnancy.

Ceftazidime is excreted in breast milk, so caution should be exercised when prescribing the drug to the mother during breastfeeding.

No data confirming embryotoxic or teratogenic effects of ceftazidime have been obtained.

Use in Renal Impairment

For patients with impaired renal function, adjustment of the dosage regimen is required because Ceftazidime is excreted by the kidneys unchanged.

The initial dose is 1 g. The maintenance dose is selected depending on the glomerular filtration rate.

Maintenance doses of ceftazidime in renal failure are presented in Table 1.

Table 1.

*The maintenance dose is prescribed every 12 hours

Pediatric Use

It is possible to use according to indications and in doses that take into account the patient’s age.

Geriatric Use

For elderly patients, especially those over 80 years of age, Fortum is recommended to be prescribed at a dose not exceeding 3 g/day.

Special Precautions

If an allergic reaction to Ceftazidime develops, the drug should be discontinued immediately. In case of hypersensitivity reactions, the use of epinephrine, hydrocortisone, antihistamines, and other emergency measures may be indicated.

When cephalosporins are taken concomitantly in high doses with nephrotoxic drugs, such as aminoglycosides and diuretics (furosemide), renal function should be monitored. However, there is no evidence that Ceftazidime at therapeutic doses impairs renal function.

Since Ceftazidime is eliminated by the kidneys, in patients with renal insufficiency, the dose of the drug should be reduced according to the degree of renal impairment.

Prolonged use of broad-spectrum antibiotics, including Fortum, may lead to the overgrowth of non-susceptible microorganisms (e.g., Candida, Enterococcus spp.), which may require discontinuation of treatment or appropriate therapy. The patient’s condition should be constantly assessed during treatment.

During treatment with Fortum, some initially sensitive strains of Enterobacter spp. and Serratia spp. may develop resistance. Therefore, if necessary, during the treatment of infections caused by these microorganisms, antibiotic susceptibility testing should be performed periodically.

Ceftazidime does not affect the results of enzymatic methods for determining glucose in urine, but may slightly affect the results of copper reduction tests (Benedict’s, Fehling’s, Clinitest).

Ceftazidime does not affect the results of creatinine determination by the alkaline picrate method.

Overdose

Symptoms neurological disorders (including encephalopathy, convulsions, coma).

Treatment symptomatic and supportive therapy should be administered. The serum concentration of ceftazidime may be reduced by hemodialysis or peritoneal dialysis.

Drug Interactions

Concomitant administration of high doses of ceftazidime and nephrotoxic drugs may have an adverse effect on renal function.

“Loop” diuretics, aminoglycosides, vancomycin, clindamycin reduce the clearance of ceftazidime, thereby increasing the risk of nephrotoxic action.

Bacteriostatic antibiotics (including chloramphenicol) reduce the effect of beta-lactam antibiotics.

Pharmaceutical Interactions

Fortum is compatible with most solutions for intravenous administration.

However, Ceftazidime is less stable in sodium bicarbonate solution, so it is not recommended for use as a solvent.

Fortum is pharmaceutically incompatible with aminoglycosides, heparin, vancomycin, chloramphenicol. Chloramphenicol acts as an antagonist of ceftazidime and other cephalosporins.

When vancomycin is added to a ceftazidime solution, precipitation is observed; therefore, it is recommended to flush the infusion system between administrations of these two drugs.

Storage Conditions

List B. The drug should be stored in a light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

After reconstitution, Fortum solutions can be stored for 24 hours at room temperature (not above 25°C (77°F)) or for 7 days in a refrigerator.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.