Calculation of the Total Iron Deficit

Cosmofer® - LOW Molecular Weight Dextran

Therapeutic indications
For adults only -  
[CosmoFer® should not be used for children under 14 years. There is no documentation for efficacy and safety per the manufacturer. ]

CosmoFer® is indicated for the treatment of iron deficiency in the following indications:
• When oral iron preparations cannot be used, e.g. due to intolerance, or in case of demonstrated lack of effect of oral iron therapy
• Where there is a clinical need to deliver iron rapidly to iron stores.
The diagnosis of iron deficiency must be based on appropriate laboratory tests (e.g. Serum ferritin, serum iron, transferrin saturation and hypochromic red cells).

Test dose: (all routes of administration)
Before administering the first dose to a new patient, a test dose of CosmoFer® corresponding to 25 mg iron or equal to 0.5 ml solution must be administered. If no adverse reactions are seen after 60 minutes, the remaining dose can be given.

Anaphylactoid reactions to CosmoFer® are usually evident within a few minutes, and close observation is necessary to ensure recognition. If at any time during the intravenous administration of CosmoFer®, any
signs of a hypersensitivity reaction or intolerance are detected, administration must be stopped immediately. Resuscitative medication and personnel trained to evaluate and rescuscitate anaphylaxis should be available whenever a dose of iron dextran is administered.

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 elderly
The total cumulative dose of CosmoFer® is determined by hemoglobin 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 hemoglobin 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.

Subsequent doses
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 1 hour after completion.  Total Dose Infusion (TDI) has been associated with an increased incidence of adverse reactions, in particular delayed hypersensitivity–like reactions. The intravenous administration of CosmoFer® by the total dose infusion method should be restricted to hospital use only.

Injection into dialyzer:
CosmoFer® may be administered during a hemodialysis session directly into the venous limb of the dialyzer under the same procedures as outlined for intravenous administration.

Intramuscular injection:
Following a test dose prior to the first injection the entire dose is administered at once for subsequent intramuscular injections. 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 minimize 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 minimize leakage up the injection track, the patient should be encouraged not to rub the injection site.

Contraindications
Non-iron deficiency anemia (e.g. hemolytic anaemia). Iron overload or disturbances in utilization of iron (e.g. hemochromatosis, hemosiderosis). Patients with a history of asthma, allergic eczema or other atopic allergy should not be treated by intravenous injection. Drug hypersensitivity including iron mono- or disaccharide complexes and dextran. Decompensated liver cirrhosis and hepatitis. Acute or chronic infection, because parenteral iron administration may exacerbate bacterial or viral infections. Rheumatoid arthritis with symptoms or signs of active inflammation. Acute renal failure.

Special warning and precautions for use
The use of CosmoFer®, as with the parenteral use of other iron-carbohydrate complexes, carries a risk of immediate severe and potentially lethal anaphylactoid reactions. Patients should be closely observed during and immediately after administration. The risk is enhanced for patients with known (medical) allergy. CosmoFer® may only be administered when facilities and equipment for handling acute anaphylactic reactions are available, including an injectable 1:1000 adrenaline solution. Additional treatment with antihistamines and/or corticosteroids should be given as appropriate. There is particularly increased risk of allergic reactions in patients with immune or inflammatory conditions (e.g. systemic lupus erythematous, rheumatoid arthritis). When parenteral iron therapy is considered essential in patients with asthma, allergic disorders and inflammatory disorders, the intramuscular route is to be preferred. The intramuscular and subcutaneous injection of iron-carbohydrate complexes in very large doses under experimental conditions in animals produced sarcoma in rats, mice, rabbits, possibly hamsters but not in guinea pigs. Cumulative information and independent assessment indicate that the risk of sarcoma formation in man is minimal. Hypotensive episodes may occur if intravenous injection is administered too rapidly.

Pregnancy and lactation
There are no adequate data from the use of CosmoFer® in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). CosmoFer® should not be used during the first trimester of pregnancy. If the benefit of CosmoFer®-treatment is judged to outweigh the potential risk to the fetus, it is recommended that treatment, should be confined to the second and third trimester, if treatment is clearly necessary. It is unknown whether the complex iron-dextran is excreted in human or animal breast milk. It is preferable to not use CosmoFer® during breast-feeding.

Background Info:

References:

1. Pharmacosmos A/S, CosmoFer® low molecular weight (Mw) iron dextran. https://www.cosmofer.com/Cosmofer.html, (2009).
2. Updated references are being reviewed (August 2012)