· The following sections have been amended to read as follows:
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One millilitre of solution contains 20mg of iron as iron sucrose (iron (III)-hydroxide sucrose complex)
Each 5 ml ampoule of Venofer contains 100 mg iron as iron sucrose (iron (III)-hydroxide sucrose complex)
Each 5 ml vial of Venofer contains 100 mg iron as iron sucrose (iron (III)-hydroxide sucrose complex)
For a full list of excipients, see 6.1.
4.2. Posology and Method of Administration
Administration: Venofer must only be administered by the intravenous route. This may be by a slow intravenous injection or by an intravenous drip infusion.
Before administering the first dose to a new patient, a test dose of Venofer should be given. Venofer must not be used for intramuscular injection.
Adults and the elderly: The total cumulative dose of Venofer, equivalent to the total iron deficit (mg), is determined by the haemoglobin level and body weight. The dose for Venofer must be individually determined for each patient according to the total iron deficit calculated with the following formula:
|
Total iron deficit [mg]
|
=
|
body weight [kg] x (target Hb - actual Hb) [g/l] x 0.24* + depot iron [mg]
|
• Below 35 kg body weight: target Hb = 130 g/l and depot iron = 15 mg/kg body weight
• 35 kg body weight and above: target Hb = 150 g/l and depot iron = 500 mg
|
*Factor 0.24 = 0.0034 x 0.07 x 1000
|
(Iron content of haemoglobin ≅ 0.34%; Blood volume ≅ 7% of body weight; Factor 1000 = conversion from g to mg)
|
The total amount of Venofer required is determined from either the above calculation or the following dosage table:
|
Body Weight[kg]
|
Total number of ampoules Venofer to be administered:
(1 ampoule of Venofer corresponds to 5ml)
|
|
Hb60g/l
|
Hb75g/l
|
Hb90g/l
|
Hb105g/l
|
|
30
|
9.5
|
8.5
|
7.5
|
6.5
|
|
35
|
12.5
|
11.5
|
10
|
9
|
|
40
|
13.5
|
12
|
11
|
9.5
|
|
45
|
15
|
13
|
11.5
|
10
|
|
50
|
16
|
14
|
12
|
10.5
|
|
55
|
17
|
15
|
13
|
11
|
|
60
|
18
|
16
|
13.5
|
11.5
|
|
65
|
19
|
16.5
|
14.5
|
12
|
|
70
|
20
|
17.5
|
15
|
12.5
|
|
75
|
21
|
18.5
|
16
|
13
|
|
80
|
22.5
|
19.5
|
16.5
|
13.5
|
|
85
|
23.5
|
20.5
|
17
|
14
|
|
90
|
24.5
|
21.5
|
18
|
14.5
|
To convert Hb(mM) to Hb(g/l), multiply the former by 16.1145.
Dosage: The total single dose must not exceed 200 mg of iron given not more than three times per week.If the total necessary dose exceeds the maximum allowed single dose,then the administration has to be split.
Children: The use of Venofer has not been adequately studied in children and, therefore, Venofer is not recommended for use in children.
Intravenous drip infusion: Venofer must be diluted only in sterile 0.9% m/V sodium chloride solution:
• 5 ml Venofer (100 mg iron)
in max. 100 ml sterile 0.9% m/V sodium chloride solution
• 10 ml Venofer (200 mg iron)
in max. 200 ml sterile 0.9% m/V sodium chloride solution
For stability reasons, dilutions to lower Venofer concentrations are not permissible.
Dilution must take place immediately prior to infusion and the solution should be administered as follows:
• 100 mg iron (5 ml Venofer) in at least 15 minutes
• 200 mg iron (10ml Venofer) in at least 30 minutes
The first 25 mg of iron (i.e. 25 ml of solution) should be infused as a test dose over a period of 15 minutes. If no adverse reactions occur during this time then the remaining portion of the infusion should be given at an infusion rate of not more than 50 ml in 15 minutes.
Intravenous injection: Venofer may be administered by slow intravenous injection at a rate of 1 ml undiluted solution per minute (i.e. 5 minutes per ampoule) and not exceeding 2 ampoules Venofer (200 mg iron) per injection. Before administering a slow intravenous injection, a test dose of 1 ml (20 mg of iron) should be injected slowly over a period of 1 to 2 minutes. If no adverse events occur within 15 minutes of completing the test dose, then the remaining portion of the injection may be given.
Injection into dialyser: Venofer may be administered during a haemodialysis session directly into the venous limb of the dialyser under the same procedures as those outlined for intravenous injection.
4.8. Undesirable Effects
The most frequently reported adverse drug reactions (ADRs) of Venofer in clinical trials were transient taste perversion, hypotension, fever and shivering, injection site reactions and nausea, occurring in 0.5 to 1.5% of the patients. Non-serious anaphylactoid reactions occurred rarely.
In general anaphylactoid reactions are potentially the most serious adverse reactions (see “Special warnings and Precautions for Use” section 4.4).
In clinical trials, the following adverse drug reactions have been reported in temporal relationship with the administration of Venofer, with at least a possible causal relationship:
Nervous system disorders
Common ( > 1/100, < 1/10): transient taste perversions (in particular metallic taste).
Uncommon ( > 1/1000, < 1/100): headache; dizziness.
Rare ( > 1/10000, < 1/1000): paraesthesia, syncope, loss of consciousness, burning sensation
Cardio-vascular disorders
Uncommon ( > 1/1000, < 1/100): hypotension and collapse; tachycardia and palpitations.
Rare ( > 1/10000, < 1/1000): hypertension.
Respiratory, thoracic and mediastinal disorders
Uncommon ( > 1/1000, < 1/100): bronchospasm, dyspnoea.
Gastrointestinal disorders
Uncommon ( > 1/1000, < 1/100): nausea; vomiting; abdominal pain; diarrhoea.
Skin and subcutaneous tissue disorders
Uncommon (> 1/1000, < 1/100): pruritus; urticaria; rash, exanthema, erythema.
Musculoskeletal, connective tissue and bone disorders
Uncommon (> 1/1000, < 1/100): muscle cramps, myalgia.
General disorders and administration site disorders
Uncommon ( > 1/1000, < 1/100): fever, shivering, flushing; chest pain and tightness. Injection site disorders such as superficial phlebitis, burning, swelling.
Rare ( > 1/10000, < 1/1000): arthralgia, peripheral oedema; fatigue, asthenia; malaise, feeling hot, oedema.
Immune system disorders
Rare ( > 1/10000, < 1/1000): anaphylactoid reactions
Moreover, in spontaneous reports the following adverse reactions have been reported:
Isolated cases: reduced level of consciousness, light-headed feeling, confusion, angio-oedema; swelling of joints, hyperhidrosis, back pain, bradycardia, chromaturia
6.5. Nature and Contents of Container
5 ml solution in one ampoule (type I glass) in pack sizes of 5.
5 ml solution in one vial (type I glass) in pack sizes of 5.
6.6. Special precautions for disposal and other handling
Ampoules or vials should be visually inspected for sediment and damage before use.
Only those with sediment free and homogenous solution must be used.
The diluted solution must appear as brown and clear.
See also 6.3 shelf-life.
Each ampoule or vial of Venofer is intended for single use only. Discard any remaining contents after first use.
Please note the following key changes made to section 4.8 (Undesirable effects).
· Under subheading Nervous System Disorders; syncope, loss of consciousness and burning sensation have been added as rare (>1/10000, <1/1000) undesirable effects.
· Under subheading Cardio-Vascular Disorders; hypertension has been added as a rare (>1/10000, <1/1000) undesirable effect.
· Under subheading General Disorders and Administration Site Disorders; anaphylactoid reactions has been removed and the undesirable effects of feeling hot and oedema have been added as rare (>1/10000, <1/1000)
· A further subheading has been added to section 4.8 titled Immune System Disorders. Listing anaphylactoid reactions as rare (>1/10000, <1/1000) undesirable effect.
· The contact details in section 7 (Marketing Authoristation Holder) has been updated from:
Vifor France Sa
123, rue Jules Guesde
92300 Levallois-Perret
France
To
Vifor France SA
7-13, Bd Paul Emile Victor
92200 Neuilly sur-Seine
France
Tel. +33 (0) 1 41 06 58 90
Fax. +33 (0)1 41 06 58 99
Email: contact@vifor-france.fr
· The Ireland Marketing Authorisation Number PA 949/1/1 and date of first authorization/renewal of the authorization 20.03.2000 / 08.06.2003 have been removed from sections 8 (MARKETING AUTHORISATION NUMBER(S)) and 9 (DATE OF FIRST AUTHORISATION / RENEWAL OF AUTHORISATION) , respectively.
· The date of revision of text has been updated from August 2006 to 01.12.2008
