FORTUM Powder for solution for injection or infusion Ref.[27719] Active ingredients: Ceftazidime

Posology

Table 1. Adults and children ≥40 kg:

¹ In adults with normal renal function 9 g/day has been used without adverse effects.
^* When associated with, or suspected to be associated with, any of the infections listed in 4.1.

Table 2. Children <40 kg:

¹ In neonates and infants ≤ 2 months, the serum half life of ceftazidime can be three to four times that in adults.
^* Where associated with, or suspects to be associated with, any of the infections listed in section 4.1.

Paediatric population

The safety and efficacy of Fortum administered as continuous infusion to neonates and infants ≤2 months has not been established.

Elderly

In view of the age related reduced clearance of ceftazidime in elderly patients, the daily dose should not normally exceed 3 g in those over 80 years of age.

Hepatic impairment

Available data do not indicate the need for dose adjustment in mild or moderate liver function impairment. There are no study data in patients with severe hepatic impairment (see also section 5.2). Close clinical monitoring for safety and efficacy is advised.

Renal impairment

Ceftazidime is excreted unchanged by the kidneys. Therefore, in patients with impaired renal function, the dosage should be reduced (see also section 4.4).

An initial loading dose of 1 g should be given. Maintenance doses should be based on creatinine clearance:

Table 3. Recommended maintenance doses of Fortum in renal impairment – intermittent infusion:

Adults and children ≥40 kg:

In patients with severe infections the unit dose should be increased by 50% or the dosing frequency increased. In children the creatinine clearance should be adjusted for body surface area or lean body mass.

Children <40 kg:

^* The serum creatinine values are guideline values that may not indicate exactly the same degree of reduction for all patients with reduced renal function.
^** Estimated based on body surface area, or measured.

Close clinical monitoring for safety and efficacy is advised.

Table 4. Recommended maintenance doses of Fortum in renal impairment – continuous infusion:

Adults and children ≥40 kg:

Caution is advised in dose selection. Close clinical monitoring for safety and efficacy is advised.

Children <40 kg:

The safety and effectiveness of Fortum administered as continuous infusion in renally impaired children <40 kg has not been established, Close clinical monitoring for safety and efficacy is advised.

If continuous infusion is used in children with renal impairment, the creatinine clearance should be adjusted for body surface area or lean body mass.

Haemodialysis

The serum half-life during haemodialysis ranges from 3 to 5 h.

Following each haemodialysis period, the maintenance dose of ceftazidime recommended in the tables 5 & 6 should be repeated.

Peritoneal dialysis

Ceftazidime may be used in peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD).

In addition to intravenous use, ceftazidime can be incorporated into the dialysis fluid (usually 125 to 250mg for 2 litres of dialysis solution).

For patients in renal failure on continuous arterio-venous haemodialysis or high-flux haemofiltration in intensive therapy units: 1 g daily either as a single dose or in divided doses. For low-flux haemofiltration, follow the dose recommended under renal impairment.

For patients on veno-venous haemofiltration and veno-venous haemodialysis, follow the dosage recommendations in tables 5 & 6 below.

Table 5. Continuous veno-venous haemofiltration dose guidelines:

¹ Maintenance dose to be administered every 12 h.

Table 6. Continuous veno-venous haemodialysis dose guidelines:

¹ Maintenance dose to be administered every 12 h.

Method of administration

The dose depends on the severity, susceptibility, site and type of infection and on the age and renal function of the patient.

Fortum 1 g should be administered by intravenous injection or infusion, or by deep intramuscular injection. Recommended intramuscular injection sites are the upper outer quadrant of the gluteus maximus or lateral part of the thigh. Fortum solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids. The standard recommended route of administration is by intravenous intermittent injection or intravenous continuous infusion. Intramuscular administration should only be considered when the intravenous route is not possible or less appropriate for the patient.

Overdose can lead to neurological sequelae including encephalopathy, convulsions and coma.

Symptoms of overdose can occur if the dose is not reduced appropriately in patients with renal impairment (see sections 4.2 and 4.4)

Serum levels of ceftazidime can be reduced by haemodialysis or peritoneal dialysis.

3 years.

After reconstitution:

Chemical and physical in-use stability has been demonstrated for 6 days at 4°C and 9 hours at 25°C.

From a microbiological point of view, the reconstituted solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

After dilution:

Chemical and physical in-use stability has been demonstrated for 6 days at 4°C and 9 hours at 25°C.

From a microbiological point of view, the reconstituted and diluted solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

Store below 25°C.

Keep vials in the outer carton to protect from light.

For storage conditions after reconstitution see section 6.3.

Fortum 1 g powder for solution for injection or infusion is packaged in clear Ph.Eur.Type III glass 17 ml, 26 ml, 60 ml or 77 ml vial with a bromobutyl rubber plug and a flip-off type aluminium overseal.

Packs of 1, 5, 10, 50 or 100 vials.

Not all pack sizes may be marketed.

All sizes of vials of Fortum are supplied under reduced pressure. As the product dissolves, carbon dioxide is released and a positive pressure develops. Small bubbles of carbon dioxide in the constituted solution may be ignored.

Instructions for constitution

See table 7 and table 8 for addition volumes and solution concentrations, which may be useful when fractional doses are required.

Table 7. Powder for Solution for Injection:

Note: The resulting volume of the solution of ceftazidime in reconstitution medium is increased due to the displacement factor of the drug product resulting in the listed concentrations in mg/ml presented in the above table.

|Table 8. Powder for Solution for Infusion:

^* Addition should be in two stages.

Note: The resulting volume of the solution of ceftazidime in reconstitution medium is increased due to the displacement factor of the drug product resulting in the listed concentrations in mg/ml presented in the above table.

Solutions range in colour from light yellow to amber depending on concentration, diluents and storage conditions used. Within the stated recommendations, product potency is not adversely affected by such colour variations.

Ceftazidime at concentrations between 1 mg/ml and 40 mg/ml is compatible with:

• sodium chloride 9 mg/ml (0.9%) solution for injection
• M/6 sodium lactate injection
• compound sodium lactate injection (Hartmann’s solution)
• 5% dextrose injection
• 0.225% sodium chloride and 5% dextrose injection
• 0.45% sodium chloride and 5% dextrose injection
• 0.9% sodium chloride and 5% dextrose injection
• 0.18% sodium chloride and 4% dextrose injection
• 10% dextrose injection
• Dextran 40 injection 10% in 0.9% sodium chloride injection
• Dextran 40 injection 10% in 5% dextrose injection
• Dextran 70 injection 6% in 0.9% sodium chloride injection
• Dextran 70 injection 6% in 5% dextrose injection

Ceftazidime at concentrations between 0.05 mg/ml and 0.25 mg/ml is compatible with Intra-peritoneal Dialysis Fluid (Lactate).

Ceftazidime at concentrations detailed in Table 7 may be constituted for intramuscular use with 0.5% or 1% Lidocaine Hydrochloride Injection.

Preparation of solution for bolus injection:

1. Insert the syringe needle through the vial closure and inject the recommended volume of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.
2. Shake to dissolve: carbon dioxide is released and a clear solution will be obtained in about 1 to 2 minutes.
3. Invert the vial. With the syringe plunger fully depressed, insert the needle through the vial closure and withdraw the total volume of solution into the syringe (the pressure in the vial may aid withdrawal). Ensure that the needle remains within the solution and does not enter the head space. The withdrawn solution may contain small bubbles of carbon dioxide; they may be disregarded.

These solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids. Ceftazidime is compatible with the intravenous fluids listed above.

Preparation of solutions for iv infusion from ceftazidime injection in standard vial presentation (mini-bag or burette-type set):

Prepare using a total of 50 ml of compatible diluents (listed above), added in TWO stages as below:

1. Introduce the syringe needle through the vial closure and inject 10 ml of diluent.
2. Withdraw the needle and shake the vial to give a clear solution.
3. Do not insert a gas relief needle until the product has dissolved. Insert a gas relief needle through the vial closure to relieve the internal pressure.
4. Transfer the reconstituted solution to final delivery vehicle (e.g. mini-bag or burette-type set) making up a total volume of at least 50 ml, and administer by intravenous infusion over 15 to 30 min.

Note: To preserve product sterility, it is important that the gas relief needle is not inserted through the vial closure before the product has dissolved.

Any residual antibiotic solution should be discarded.

For single use only.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.