1. Name Of The Medicinal Product
Ferinject®
2. Qualitative And Quantitative Composition
One millilitre of solution contains 50 mg of iron as ferric carboxymaltose.
Each 2 ml vial contains 100 mg of iron as ferric carboxymaltose.
Each 10 ml vial contains 500 mg of iron as ferric carboxymaltose.
Ferinject® contains sodium hydroxide. One millilitre of solution contains up to 0.24 mmol (5.5 mg) sodium, see section 4.2. For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Solution for injection/infusion. Dark brown, non-transparent, aqueous solution.
4. Clinical Particulars
4.1 Therapeutic Indications
Ferinject® is indicated for treatment of iron deficiency when oral iron preparations are ineffective or cannot be used.
The diagnosis must be based on laboratory tests.
4.2 Posology And Method Of Administration
Calculation of the cumulative dose
The adequate cumulative dose of Ferinject® must be calculated for each patient individually and must not be exceeded. For overweight patients, a normal body weight/blood volume relation should be assumed when determining the iron requirement. The dose of Ferinject® is expressed in mg of elemental iron.
The cumulative dose required for Hb restoration and repletion of iron stores is calculated by the following Ganzoni formula:
Cumulative iron deficit [mg] =
body weight [kg] x (target Hb* - actual Hb) [g/dl]** x 2.4*** +
iron storage depot [mg]****
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For patients
For patients> 66 kg: the calculated cumulative dose is to be rounded up to the nearest 100 mg.
Patients may continue to require therapy with Ferinject® at the lowest dose necessary to maintain target levels of haemoglobin, and other laboratory values of iron storage parameters within acceptable limits.
Maximum tolerated single dose
The adequate cumulative dose of Ferinject® must be calculated for each patient individually and must not be exceeded.
Intravenous bolus injection
Ferinject® may be administered by intravenous injection up to a maximum single dose of 4 ml (200 mg of iron) per day but not more than three times a week.
Intravenous drip infusion
Ferinject® may be administered by intravenous infusion up to a maximum single dose of 20 ml of Ferinject® (1000 mg of iron) but not exceeding 0.3 ml of Ferinject® (15 mg of iron) per kg body weight or the calculated cumulative dose. Do not administer 20 ml (1000 mg of iron) as an infusion more than once a week.
The use of Ferinject® has not been studied in children, and therefore is not recommended in children under 14 years.
Method of administration
Ferinject® must be administered only by the intravenous route: by bolus injection, during a haemodialysis session undiluted directly into the venous limb of the dialyser, or by drip infusion. In case of drip infusion Ferinject® must be diluted only in sterile 0.9% sodium chloride solution as follows:
Dilution plan of Ferinject®for intravenous drip infusion
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Note: For stability reasons, dilutions to concentrations less than 2 mg iron/ml are not permissible.
Ferinject® must not to be administered by the intramuscular route.
4.3 Contraindications
The use of Ferinject® is contraindicated in cases of:
• known hypersensitivity to Ferinject® or to any of its excipients
• anaemia not attributed to iron deficiency, e.g. other microcytic anaemia
• evidence of iron overload or disturbances in utilisation of iron
• pregnancy in the first trimester
4.4 Special Warnings And Precautions For Use
Parenterally administered iron preparations can cause hypersensitivity reactions including anaphylactoid reactions, which may be potentially fatal (see section 5.3). Therefore, facilities for cardio-pulmonary resuscitation must be available.
In patients with liver dysfunction, parenteral iron should only be administered after careful risk/benefit assessment. Parenteral iron administration should be avoided in patients with hepatic dysfunction where iron overload is a precipitating factor, in particular Porphyria Cutanea Tarda (PCT). Careful monitoring of iron status is recommended to avoid iron overload.
Parenteral iron must be used with caution in cases of acute or chronic infection, asthma, eczema or atopic allergies. It is recommended that the administration of Ferinject® is stopped in patients with ongoing bacteraemia. In patients with chronic infection a risk/benefit evaluation has to be performed, taking into account the suppression of erythropoiesis.
Caution should be exercised to avoid paravenous leakage when administering Ferinject®. Paravenous leakage of Ferinject® at the injection site may lead to brown discolouration and irritation of the skin. In case of paravenous leakage, the administration of Ferinject® must be stopped immediately.
One millilitre of undiluted Ferinject® contains up to 0.24 mmol (5.5 mg) of sodium. This has to be taken into account in patients on a sodium-controlled diet.
The use of Ferinject® has not been studied in children.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
As with all parenteral iron preparations the absorption of oral iron is reduced when administered concomitantly.
4.6 Pregnancy And Lactation
Clinical data on pregnant women are not available. A careful risk/benefit evaluation is required before use during pregnancy.
Animal data suggest that iron released from Ferinject® can cross the placental barrier and that its use during pregnancy may influence skeletal development in the fetus.
Clinical studies showed that transfer of iron from Ferinject® to human milk was negligible (® represents a risk to the nursing child.
4.7 Effects On Ability To Drive And Use Machines
Ferinject® is unlikely to impair the ability to drive or operate machines.
4.8 Undesirable Effects
The most commonly reported ADR is headache, occurring in 3.3% of the patients.
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Immune system disorders:
Uncommon (>1/1,000, <1/100): Hypersensitivity including anaphylactoid reactions
Nervous system disorders:
Common (>1/100, <1/10): Headache, dizziness
Uncommon (>1/1,000, <1/100): Paraesthesia
Vascular disorders:
Uncommon (>1/1,000, <1/100): Hypotension, flushing
Respiratory, thoracic and mediastinal disorders:
Rare (>1/10,000, <1/1,000): Dyspnoea
Gastrointestinal disorders:
Common (>1/100, <1/10): Nausea, abdominal pain, constipation, diarrhoea
Uncommon (>1/1,000, <1/100): Dysgeusia, vomiting, dyspepsia, flatulence
Skin and subcutaneous tissue disorders:
Common (>1/100, <1/10): Rash
Uncommon >1/1,000, <1/100): Pruritus, urticaria
Musculoskeletal and connective tissue disorders:
Uncommon (>1/1,000, <1/100): Myalgia, back pain, arthralgia
General disorders and administration site conditions:
Common (>1/100, <1/10): Injection site reactions
Uncommon (>1/1,000, <1/100): Pyrexia, fatigue, chest pain, rigors, malaise, oedema peripheral
Investigations:
Common (>1/100, <1/10): Transient blood phosphorus decreased, alanine aminotransferase increased
Uncommon (>1/1,000, <1/100): Aspartate aminostransferase increased, gamma-glutamyltransferase increased, blood lactate dehydrogenase increased
4.9 Overdose
Administration of Ferinject® in quantities exceeding the amount needed to correct iron deficit at the time of administration may lead to accumulation of iron in storage sites eventually leading to haemosiderosis. Monitoring of iron parameters such as serum ferritin and transferrin saturation may assist in recognising iron accumulation.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Iron trivalent, parenteral preparation.
ATC Code: B03A C01
Ferinject® solution for injection/infusion contains iron in a stable ferric state as a complex with a carbohydrate polymer designed to release utilisable iron to the iron transport and storage proteins in the body (ferritin and transferrin). Clinical studies showed that the haematological response and the filling of the iron stores was faster after intravenous administration of Ferinject® than with orally administered comparators.
Using positron emission tomography (PET) it was demonstrated that red cell utilisation of 59Fe and 52Fe from Ferinject® ranged from 61% to 99%. Patients with iron deficiency showed utilisation of radio-labelled iron of 91% to 99% after 24 days, and patients with renal anaemia showed utilisation of radio-labelled iron of 61% to 84% after 24 days.
One millilitre of undiluted Ferinject® contains less than 75μg aluminium. This should be considered in the treatment of patients undergoing dialysis.
5.2 Pharmacokinetic Properties
Using positron emission tomography (PET) it was demonstrated that 59Fe and 52Fe from Ferinject® was rapidly eliminated from the blood, transferred to the bone marrow, and deposited in the liver and spleen.
After administration of a single dose of Ferinject® of 100 to 1,000 mg of iron in iron deficient patients, maximum iron levels of 37 µg/ml up to 333 µg/ml after 15 minutes to 1.21 hours respectively are obtained. The volume of the central compartment corresponds well to the volume of the plasma (approximately 3 litres).
The iron injected or infused was rapidly cleared from the plasma, the terminal half-life ranged from 7 to 12 hours, the mean residence time (MRT) from 11 to 18 hours. Renal elimination of iron was negligible.
5.3 Preclinical Safety Data
Pre-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeat dose toxicity and genotoxicity. Animal studies indicate that iron released from Ferinject® does cross the placental barrier and is excreted in milk. In reproductive toxicology studies using iron replete animals Ferinject® was associated with minor skeletal abnormalities in the fetus. No long-term studies in animals have been performed to evaluate the carcinogenic potential of Ferinject®. No evidence of allergic or immunotoxic potential has been observed. A controlled in-vivo test demonstrated no cross-reactivity of Ferinject® with anti-dextran antibodies. No local irritation or intolerance was observed after intravenous administration.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Sodium hydroxide (for pH adjustment)
Hydrochloric acid (for pH adjustment)
Water for injection
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products than those mentioned in section 6.6.
The compatibility with containers other than polyethylene and glass is not known.
6.3 Shelf Life
Shelf-life of the product as packaged for sale:
3 years.
Shelf-life after first opening of the container:
From a microbiological point of view, preparations for parenteral administration should be used immediately.
Shelf-life after dilution with sterile 0.9% sodium chloride solution:
From a microbiological point of view, preparations for parenteral administration should be used immediately after dilution with sterile 0.9% sodium chloride solution.
6.4 Special Precautions For Storage
Store in the original package. Do not store above 30°C. Do not refrigerate or freeze.
6.5 Nature And Contents Of Container
2 ml of solution in a vial (type I glass) with bromobutyl rubber stopper and aluminium cap.
10 ml of solution in a vial (type I glass) with bromobutyl rubber stopper and aluminium cap.
6.6 Special Precautions For Disposal And Other Handling
Inspect vials visually for sediment and damage before use. Use only those containing sediment-free, homogeneous solution.
Each vial of Ferinject® is intended for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
Ferinject® must only be mixed with sterile 0.9% sodium chloride solution. No other intravenous dilution solutions and therapeutic agents should be used, as there is the potential for precipitation and/or interaction. For dilution instructions, see section 4.2.
7. Marketing Authorisation Holder
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
8. Marketing Authorisation Number(S)
UK: PL 15240/0002
Ireland: PA 0949/004/001
9. Date Of First Authorisation/Renewal Of The Authorisation
19.07.2007
10. Date Of Revision Of The Text
09.07.2009
Distributed by
Syner-Med (PP) Ltd
2nd Floor, Beech House
840 Brighton Road
Purley
Surrey
CR8 2 BH
Tel: 0845 634 2100
Fax: 0845 634 2101
Int Tel: +44 208 655 6380
Int Fax: +44 208 655 6398
Ferinject® is a registered trademark
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