- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.
Administration:CosmoFer® solution for infusion and injection can be administered by an intravenous drip infusion or by a slow intravenous injection of which the intravenous drip infusion is the preferred route of administration, as this may help to reduce the risk of hypotensive episodes. However, CosmoFer® may also be administered as undiluted solution intramuscularly.
Adults and elderlyThe total cumulative dose of CosmoFer® is determined by haemoglobin level and body weight. The dose and dosage schedule for CosmoFer® must be individually estimated for each patient based on a calculation of the total iron deficit.
Children (under 14 years)CosmoFer® should not be used for children. There is no documentation for efficacy and safety.
Dosage:The normal recommended dosage schedule is 100-200 mg iron corresponding to 2-4 ml, two or three times a week depending on the haemoglobin level. However, if clinical circumstances require rapid delivery of iron to the body iron stores CosmoFer® may be administered as a total dose infusion up to a total replacement dose corresponding to 20 mg iron/kg body weight.The CosmoFer® injection should not be administered concomitantly with oral iron preparations as the absorption of oral iron will be reduced (please refer to section 4.5).
Intravenous drip infusion:CosmoFer® must be diluted only in 0.9% sodium chloride solution (normal saline) or in 5% glucose solution. CosmoFer® in a dose of 100-200 mg iron (2-4ml) may be diluted in 100 ml. On each occasion the first 25 mg of iron should be infused over a period of 15 minutes. If no adverse reactions occur during this time the remaining portion of the infusion should be given at an infusion rate of not more than 100 ml in 30 minutes.
Intravenous injection:CosmoFer® may be administered in a dose of 100 200 mg iron (2-4 ml) by slow intravenous injection (0.2 ml/min) preferably diluted in 10 20 ml 0.9% sodium chloride or 5% glucose solution. On each occasion before administering a slow intravenous injection, 25 mg of iron should be injected slowly over a period of 1 to 2 minutes. If no adverse reactions occur within 15 minutes, the remaining portion of the injection may be given.
Total dose infusion:Immediately before administration the total amount of CosmoFer® required, determined from the dosage table or by calculation, is added aseptically to the required volume, usually 500 ml of sterile normal sodium chloride or 5% glucose solutions. The total amount of CosmoFer®, up to 20 mg/kg bodyweight, is infused intravenously over 4 6 hours. The first 25 mg of iron should be infused over a period of 15 minutes. The patient must be kept under close medical observation during this period. If no adverse reactions occur during this time, then the remaining portion of the infusion should be given. The rate of infusion may be increased progressively to 45 60 drops per minute. Patients should be observed carefully during the infusion and for at least 30 minutes after completion. Total Dose Infusion (TDI) has been associated with an increased incidence of adverse reactions, in particular delayed hypersensitivitylike reactions. The intravenous administration of CosmoFer® by the total dose infusion method should be restricted to hospital use only.
Injection into dialyser:CosmoFer® may be administered during a haemodialysis session directly into the venous limb of the dialyser under the same procedures as outlined for intravenous administration.
Intramuscular injection:The total amount of CosmoFer® required is determined either from the dosage table or by calculation. It is administered as a series of undiluted injections of up to 100 mg iron (2.0 ml) each determined by the patient's body weight. If the patient is moderately active, injections may be given daily into alternate buttocks. In inactive or bedridden patients, the frequency of injections should be reduced to once or twice weekly.CosmoFer® must be given by deep intramuscular injection to minimise the risk of subcutaneous staining. It should be injected only into the muscle mass of the upper outer quadrant of the buttock - never into the arm or other exposed areas. A 20 - 21 gauge needle at least 50 mm long should be used for normal adults. For obese patients the length should be 80 - 100 mm whereas for small adults a shorter and smaller needle (23 gauge x 32 mm) is used. The patient should be lying in the lateral position with the injection site uppermost, or standing bearing their weight on the leg opposite the injection site. To avoid injection or leakage into the subcutaneous tissue, a Z-track technique (displacement of the skin laterally prior to injection) is recommended. CosmoFer® is injected slowly and smoothly. It is important to wait for a few seconds before withdrawing the needle to allow the muscle mass to accommodate the injection volume. To minimise leakage up the injection track, the patient should be encouraged not to rub the injection site.
Calculation of dose:
a) Iron replacement in patients with iron deficiency anaemia:Factors contributing to the formula are shown below. The required dose has to be individually adapted according to the total iron deficit calculated by the following formula haemoglobin in g/l or mmol/l.Total dose (mg Fe) Hb in g/l:(Body weight (kg) x (target Hb - actual Hb) (g/l) x 0.24) + mg iron for iron storesThe factor 0.24 is derived from the following assumptions:a) Blood volume 70 ml/kg of body weight ≈ 7% of body weightb) Iron content of haemoglobin 0.34%Factor 0.24 = 0.0034 x 0.07 x 1000 (conversion from g to mg).Total dose (mg Fe) Hb in mmol/l:Body weight in kg x (target Hb in mmol/l actual Hb in mmol/l) x 3.84 + mg iron for iron stores.The factor 3.84 is derived from the following assumptions:a) Blood volume 70 ml/kg of body weight ≈ 7% body weightb) Iron content of haemoglobin 0.34%c) Factor for conversion from haemoglobin g/l to mmol/l is 0.06205Factor 3.84 = 0.0034 x 0.07 x 1000 / 0.06205The table below shows the number of millilitres of CosmoFer® injection solution to be used at various degrees of iron deficiency anaemia.The figures in the table below are based on a target haemoglobin of 150 g/l or 9.3 mmol/l and iron stores of 500 mg which apply to a body weight exceeding 35 kg.Although there are significant variations in body build and weight distribution among males and females, the accompanying table and formula represent a convenient means for estimating the total iron required. This total iron requirement reflects the amount of iron needed to restore haemoglobin concentration to normal or near normal levels plus an additional allowance to provide adequate replenishment of iron stores in most individuals with moderately or severely reduced levels of haemoglobin. It should be remembered that iron deficiency anaemia will not appear until essentially all iron stores have been depleted. Therapy, thus, should aim at not only replenishment of haemoglobin iron but of iron stores as well.If the total necessary dose exceeds the maximum allowed daily dose, the administration has to be split. Evidence of a therapeutic response can be seen within a few days of administration of CosmoFer® as an increase in the reticulocyte count. Serum ferritin levels usually provide a good guide to the replenishment of iron stores. In renal dialysis patients receiving CosmoFer®, this correlation may not be valid. Total dose of CosmoFer® in Millilitres to be administered in iron deficiency anaemia
|Haemoglobin content Body weight (kg)||60 g/l ≈ 3.7 mmol/l||75 g/l ≈ 4.7 mmol/l||90 g/l ≈ 5.6 mmol/l||105 g/l ≈ 6.5 mmol/l||120 g/l ≈ 7.4 mmol/l||135 g/l ≈ 8.4 mmol/l|
b) Iron replacement for blood loss:Iron therapy in patients with blood loss should be directed toward replacement of an amount of iron equivalent to the amount of iron represented in the blood loss. The table and formula described are not applicable for simple iron replacement values. Quantitative estimates of the individual's periodic blood loss and hematocrit during the bleeding episode provide a convenient method of calculation of the required iron dose. The required CosmoFer® dose to compensate the iron deficit is calculated according to the following formulas:• If the volume of blood lost is known: The administration of 200 mg i.v. iron (4 ml CosmoFer®) results in an increase of haemoglobin which is equivalent to 1 unit blood (= 400 ml with 150 g/l Hb content or 9.3 mmol Hb/l equivalent to 0.34% of 0.4 x 150 or 204 mg iron).Iron to be replaced [mg] = number of blood units lost x 200.Millilitres of CosmoFer® needed = number of blood units lost x 4.• If the Hb level is reduced: Use the previous formula considering that the depot iron does not need to be restored. Mg iron to be replaced = body weight (kg) x 0.24 x (target Hb in g/l - actual Hb in g/l). OrMg iron to be replaced = body weight (kg) x 3.84 x (target Hb in mmol/l actual Hb in mmol/l).E.g.: body weight 60 kg, Hb deficit = 10 g/l or 0.62 mmol/l: Iron to be replaced = 60 x 0.24 x 10 = 60 x 3.84 x 0.62 = 143 mg (≈ 3 millilitres CosmoFer®)
|Organ System||Uncommon (>1/1,000, <1/100)||Rare (>1/10,000, <1/1,000)||Very rare <1/10,000|
|Blood and lymphatic system disorders||Haemolysis|
|Cardiac disorders||Arrythmia, tachycardia||Foetal bradycardia, palpitations|
|Ear and labyrinth disorders||Transient deafness|
|Gastrointestinal disorders||Nausea, emesis, abdominal pain||Diarrhoea|
|General disorders and administration site conditions||Feeling hot||Fatigue Pain and brown pigmentation at injection site|
|Immune system disorders||Anaphylactoid reactions including dyspnoea, urticaria, rashes, itching, nausea and shivering||Acute, severe anaphylactoid reactions (sudden onset of respiratory difficulty and / or cardiovascular collapse)|
|Musculoskeletal and connective tissue disorders||Cramps||Myalgias|
|Nervous system disorders||Blurred vision, numbness||Loss of consciousness, seizure, dizziness, restlessness, tremor||Headache, paresthesia|
|Respiratory, thoracic and mediastinal disorders||Dyspnea||Chest pain|
|Psychiatric disorders||Mental status changes|
|Skin and subcutaneous tissue disorders||Flushing, pruritus, rash||Angioedema, Sweating|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard
Pharmacosmos UK Limited
The White Building, 33 Kings Road, Reading, Berkshire, RG1 3AR, UK
+44 (0)1844 269 005
+44 (0)1844 269 007
+44 (0)1844 269 007
+44 (0)1844 269 005