Fortum 2g Powder for Solution - For injection or Infusion, vial - For Infusion, monovial *



Section 2:              editorial changes + addition of sodium excipient – harmonised text

Section 3:              powder description – harmonised text

Section 4.4:           sodium quantity clarification – harmonised text

Section 6.2:           administrative update – harmonised text

Sections 6.3:         Reconstituted storage and shelf life has been added on reconstitution and dilution + microbiological statements

Sections 6.4:         editorial changes update, reference to reconstituted storage conditions added – harmonised text

Section 6.5:           description update – harmonised text

Section 6.6:           instructions for constitution clarified by tables for powder for injection and powder for solution for infusion – harmonised text

Section 9:              editorial changes update

Section 4.4 – Additions of sub-headings for W&P (QRD)
Section 4.8 - To include Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) as an Adverse Event with frequency “unknown”
Section 7 – Update to MAH Address Change
Section 10 - Update date of revision of text

Change to address of the MA Holder

Section 4.2 – Changes to the method of administration and administrative changes.
Section 4.3 – changes to align with the latest QRD template.
Section 4.8- Addition of reporting details.
Section 5.1- update to bacterial susceptibility.
Section 6.6 Administrative changes.
Section 10- update to the revision of the text date.

2g (PA 1077/7/3)

 

1.       NAME OF THE MEDICINAL PRODUCT

 

Fortum 2g Powder for Solution – for Injection or Infusion, vial

                                                  - for Infusion, monovial

 

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each vial contains 2g of Ceftazidime (as pentahydrate).

When reconstituted as directed, the reconstituted solution contains 2g ceftazidime (as sodium salt).

Excipients: Contains approximately 105mg sodium per vial.

 

For a full list of excipients, see section 6.1

 

6.2     Incompatibilities

 

Fortum is less stable in Sodium Bicarbonate Injection than in other intravenous fluids.  It is not recommended as a diluent.

 

Ceftazidime and aminoglycosides should not be mixed in the same giving set or syringe. Precipitation has been reported with vanomycin added to ceftazidime in solution. Therefore, it would be prudent to flush giving sets and intravenous lines between administration of these agents.

 

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

 

 1.          NAME OF THE MEDICINAL PRODUCT

Fortum for Injection 2g Powder for Solution ¨C for Injection or Infusion, vial
                                               - for Infusion, monovial

4.4        Special Warnings and Special Precautions for Use

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Use of this anti-infective in the presence of renal insufficiency requires careful monitoring of dosage to avoid excessive accumulation in blood. Blood urea nitrogen levels are influenced by diet and by tissue breakdown, therefore renal function is more appropriately gauged by creatinine clearance. The maximum dose should be limited to 2 g in 24 hours in patients with oliguria or creatinine clearance of 50-31 ml/min.  The reason being that blood urea nitrogen levels are influenced by diet and tissue break down, therefore renal function is more appropriately gauged by creatinine clearance.

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4.5        Interactions with other Medicaments Medicinal Products and Other Forms of Interaction

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Chloramphenicol is antagonistic in vitro with ceftazidime and other cephalosporins. The clinical relevance of this finding is unknown, but if concurrent administration of ceftazidime with chloramphenicol is proposed, the possibility of antagonism should be considered.

In common with other antibiotics, ceftazidime may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

4.8        Undesirable Effects

        Local:
Repeated intravenous administration may induce thrombophlebitis. Local pain at the site of injection may follow intramuscular administration. As with other cephalosporins, there have been rare reports of toxic epidermal necrolysis.

        Hypersensitivity:
Maculopapular or urticarial rash, fever, pruritis, anaphylactic reactions and very rarely angioedema and anaphylaxis including bronchospasm and hypotension may occur.

As with other cephalosporins, there have been rare reports of erythema multiform, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Gastrointestinal:
Gastrointestinal upset including, diarrhoea; nausea; vomiting; abdominal pain, oral thrush; colitis have been reported. As with other cephalosporins, colitis may be associated with Clostridium difficile and may present as pseudomembranous colitis.

Genito-urinary:
Candidiasis and vaginitis have been reported.

Hepatobiliary tract and pancreas:
        Very rarely jaundice

        CNS:
Headache, dizziness, bad taste and paraesthesia have been reported. There have been reports of neurological sequelae including tremor, myoclonia, convulsions, and encephalopathy in patients with renal impairment in whom the dose of ceftazidime has not been appropriately reduced.

        Transient laboratory test changes:
Transient changes noted during ceftazidime therapy include eosinophilia, thrombocytosis and elevations in one or more of the hepatic enzymes, ALT (SGPT), AST (SGOT), LDH, GGT and alkaline phosphatase. As with other cephalosporins, transient elevations of blood urea, blood urea nitrogen and/or serum creatinine have been observed occasionally. Very rarely leucopenia, neutropenia, agranulocytosis, thrombocytopenia and lymphocytosis have been reported.

Data from large clinical trials (internal and published) were used to determine the frequency of very common to uncommon undesirable effects.  The frequencies assigned to all other undesirable effects were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.  

The following convention has been used for the classification of frequency:-  
very common ¡Ý1/10,
common ¡Ý1/100 and <1/10,
uncommon ¡Ý1/1000 and<1/100,
rare ¡Ý1/10,000 and <1/1000,
very rare <1/10,000.

Infections and infestations
Uncommon:        Candidiasis (including vaginitis and oral thrush)

Blood and lymphatic system disorders
Common:        Eosinophilia and thrombocytosis.

Uncommon:        Leucopenia, neutropenia, and thrombocytopenia,

Very Rare:        Lymphocytosis, haemolytic anaemia and agranulocytosis.

Immune system disorders
Very Rare:        Anaphylaxis (including bronchospasm and/or hypotension).

Nervous system disorders
Uncommon:        Headache and dizziness

Very Rare:        Paraesthesia

There have been reports of neurological sequelae including tremor, myoclonia, convulsions, encephalopathy and coma in patients with renal impairment in whom the dose of ceftazidime has not been appropriately reduced.

Vascular disorders
Common:        Thrombophlebitis with IV administration

Gastrointestinal disorders
Common:        Diarrhoea

Uncommon:        Nausea, vomiting, abdominal pain, and colitis

Very Rare:        Bad taste

As with other cephalosporins, colitis may be associated with Clostridium difficile and may present as pseudomembranous colitis.

Hepatobiliary disorders
Common:        Transient elevations in one or more of the hepatic enzymes, ALT (SGPT), AST (SOGT), LDH, GGT and alkaline phosphatase.

Very Rare:        Jaundice.

Skin and subcutaneous tissue disorders
Common:        Maculopapular or urticarial rash

Uncommon:        Pruritus

Very Rare:        Angioedema, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.  

General disorders and administration site conditions
Common:        Pain and/or inflammation after IM injection.

Uncommon:        Fever

Investigations

Uncommon:        As with some other cephalosporins, transient elevations of blood urea, blood urea nitrogen and/or serum creatinine have been observed

6.2        Incompatibilities

Fortum is less stable in Sodium Bicarbonate Injection than in other intravenous fluids.  It is not recommended as a diluent.

Ceftazidime and aminoglycosides should not be mixed in the same giving set or syringe. Precipitation has been reported with vanomycin added to ceftazidime in solution. Therefore, it would be prudent to flush giving sets and intravenous lines between the administration of these two agents.

Therefore it would be prudent to flush giving sets and i.v. lines between administration of these two agents.

6.6        Instructions for Use and Handling Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

Fortum is compatible with most commonly used intravenous fluids.

Vials of Fortum for Injection do not contain any preservatives and should be used as single-dose preparations.

All sizes of vials of Fortum for Injection and Fortum Monovial as supplied are 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.

Preparation of Solution

 

*Addition should be in 2 stages (see text).

Fortum is compatible with most commonly used intravenous fluids. However, Sodium Bicarbonate Injection is not recommended as a diluent (see 6.2 Incompatibilities).

Solutions range from light yellow to amber depending on concentration, diluent 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:
0.9% Sodium Chloride 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 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 may be constituted for intramuscular use with 0.5% or 1% Lignocaine Hydrochloride Injection.

Both components retain satisfactory potency when ceftazidime at 4 mg/ml is admixed with:
Hydrocortisone (hydrocortisone sodium phosphate) 1 mg/ml in 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
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/I or 40 m Eq/I in 0.9% Sodium Chloride Injection.

The contents of a 500g vial of Fortum for Injection, reconstituted with 1.5ml Water for Injections, may be added to metronidazole injection (500mg in 100ml) and both retain their activity.

Preparation of solutions for IM or IV bolus injection:

1. Introduce the syringe needle through the vial closure and inject the recommended volume of diluent.

2. Withdraw the needle and shake the vial to give a clear solution.

3. Invert the vial. With the syringe piston fully depressed, insert the needle into the solution.  Withdraw the total volume of solution into the syringe ensuring that the needle remains in the solution.  Small bubbles of carbon dioxide may be disregarded.

Preparation of solutions for IV infusion:

1. Introduce the syringe needle through the vial closure and introduce the syringe needle through the vial closure and inject the recommended volume of diluent.

2. Withdraw the needle and shake the vial to give a clear solution.

3. Insert a gas relief needle through the vial closure to relieve the internal pressure. With the gas relief in place, add the remainder of the diluent. Remove both gas relief needle and syringe needle; shake the vial and set up for infusion use in the normal way.

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

Preparation of solution for intravenous infusion using Fortum Monovial:

The contents of the Monovial are added to small volume infusion bags containing 0.9% Sodium Chloride Injection, or 5% Dextrose Injection, or another compatible fluid.

1. Peel off the removable top part of the label and remove the cap.

2. Insert the needle of the Monovial into the additive port of the infusion bag.

3. To activate, push the plastic needle holder of the Monovial down onto the vial shoulder until a ¡°click¡± is heard.

4. Holding it upright, fill the vial to approximately two-thirds capacity by squeezing the bag several times.

5. Shake the vial to reconstitute the Fortum.

6. On reconstitution, the Fortum will effervesce slightly.

7. With the vial uppermost, transfer the reconstituted Fortum into the infusion bag by squeezing and releasing the bag.

8. Repeat steps 4 to 7 to rinse the inside of the vial.  Dispose of the empty Monovial safely.  Check that the powder has dissolved, and that the bag has no leaks.

Preparation of Solution

*Addition of diluent should be in 2 stages (see Preparation of solutions for IV infusion).
^¡ì Please note the different reconstitution volumes for the 2g vial versus the 2g monovial. These two presentations are not interchangeable.

Vials of Fortum do not contain any preservatives and should be used as single-dose preparations.
All sizes of vials of Fortum 2g as supplied are 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.
Solutions range from light yellow to amber depending on concentration, diluent and storage conditions used. Within the stated recommendations, product potency is not adversely affected by such colour variations.
Fortum is compatible with most commonly used intravenous fluids. However, Sodium Bicarbonate Injection is not recommended as a diluent (see 6.2 Incompatibilities).

Both components retain satisfactory potency when ceftazidime at 4 mg/ml is admixed with:
Hydrocortisone (hydrocortisone sodium phosphate) 1 mg/ml in 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
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/I or 40 m Eq/I in 0.9% Sodium Chloride 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 between 1 mg/ml and 40 mg/ml is compatible with the following infusion bags:
0.9% Sodium Chloride 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 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

Preparation of solutions for IV bolus injection:
Introduce the syringe needle through the vial closure and inject the recommended volume of diluent.
Withdraw the needle and shake the vial to give a clear solution.
Invert the vial. With the syringe piston fully depressed, insert the needle into the solution.  Withdraw the total volume of solution into the syringe ensuring that the needle remains in the solution.  Small bubbles of carbon dioxide may be disregarded.

Preparation of solutions for IV infusion:
Prepare using a total of 50ml of compatible diluent added in TWO stages as below:

1.        Introduce the syringe needle through the vial closure and inject 10ml 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. When dissolution is complete, insert a gas relief needle through the vial closure to relieve the internal pressure.
4.        With the gas relief in place, add the remainder of the diluent (40ml). Remove both gas relief needle and syringe needle; shake the vial and set up for infusion use in the normal way.

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

Preparation of solution for intravenous infusion using 2g Monovial:
The contents of the Monovial are added to 100ml infusion bags containing 0.9% Sodium Chloride Injection, or 5% Dextrose Injection, or another compatible fluid.

1. Peel off the removable top part of the label and remove the cap.

2. Insert the needle of the Monovial into the additive port of the infusion bag.

3. To activate, push the plastic needle holder of the Monovial down onto the vial shoulder until a ¡°click¡± is heard.

4. Holding it upright, fill the vial to approximately two-thirds capacity by squeezing the bag several times.

5. Shake the vial to reconstitute the Fortum.

6. On reconstitution, the Fortum will effervesce slightly.

7. With the vial uppermost, transfer the reconstituted Fortum into the infusion bag by squeezing and releasing the bag.

8. Repeat steps 4 to 7 to rinse the inside of the vial. Dispose of the empty Monovial safely. Check that the powder has dissolved, and that the bag has no leaks.