MONOFER Solution for injection / infusion Ref.[8278] Active ingredients: Iron (III) isomaltoside

Calculation of the cumulative iron need

Iron replacement in patients with iron deficiency

The dose of Monofer is expressed in mg of elemental iron. The iron need and the administration schedule for Monofer must be individually established for each patient. The optimal haemoglobin target level and iron stores may vary in different patient groups and between patients. Please refer to official guidelines.

Iron deficiency anaemia will not appear until essentially all iron stores have been depleted. Iron therapy should therefore replenish both haemoglobin iron and iron stores.

After the current iron deficit has been corrected, patients may require continued therapy with Monofer to maintain target levels of haemoglobin and acceptable limits of other iron parameters.

The cumulative iron need can be determined using either the Ganzoni formula (1) or the Table below (2). It is recommended to use the Ganzoni formula in patients who are likely to require individually adjusted dosing such as patients with anorexia nervosa, cachexia, obesity, pregnancy or anaemia due to bleeding.

Haemoglobin is abbreviated Hb.

1. Ganzoni formula:

Iron need (mg iron) = Body weight^A (kg) X [Target Hb^E (g/dl) - Actual Hb (g/dl)]^B X 2.4^C + Iron for iron stores (mg iron)

^A It is recommended to use the patient’s ideal body weight for obese patients or pre-pregnancy weight for pregnant women. Ideal body weight may be calculated in a number of ways e.g. by calculating weight at BMI 25 i.e. ideal body weight = 25 * (height in m)2
^B To convert Hb [mM] to Hb [g/dl] you should multiply Hb [mM] by factor 1.61145
^C Factor 2.4 = 0.0034 × 0.07 × 10,000
0.0034: Iron content of haemoglobin is 0.34%
0.07: Blood volume 70 ml/kg of body weight ≈ 7% of body weight
10,000: The conversion factor 1 g/dl = 10,000 mg/l
^D For a person with a body weight above 35 kg, the iron stores are 500 mg or above. Iron stores of 500 mg are at the lower limit normal for small women. Some guidelines suggest using 10-15 mg iron /kg body weight.
^E Default Hb target is 15 g/dl in the Ganzoni formula. In special cases such as pregnancy consider using a lower haemoglobin target.

2. Simplified Table:

Iron need:

The treatment effect should be monitored by blood tests. To reach the target Hb-level, the cumulative iron dose may need adjustment.

Iron replacement for blood loss:

Iron therapy in patients with blood loss should supply an amount of iron equivalent to the amount of iron represented in the blood loss.

• If the Hb level is reduced: Use the Ganzoni formula considering that the depot iron does not need to be restored:

Iron need (mg iron) = Body weight (kg) X [Target Hb (g/dl) - Actual Hb (g/dl)] X 2.4

• If the volume of blood lost is known: The administration of 200 mg Monofer results in an increase of haemoglobin which is equivalent to 1 unit blood:

Iron to be replaced (mg iron) = Number of units blood lost X 200

Administration

Monitor carefully patients for signs and symptoms of hypersensitivity reactions during and following each administration of Monofer.

Monofer should only be administered when staff trained to evaluate and manage anaphylactic reactions is immediately available, in an environment where full resuscitation facilities can be assured. The patient should be observed for adverse effects for at least 30 minutes following each Monofer injection (see section 4.4).

Each IV iron administration is associated with a risk of a hypersensitivity reaction. Thus, to minimise risk the number of single IV iron administrations should be kept to a minimum.

Children and adolescents

Monofer is not recommended for use in children and adolescents <18 years due to insufficient data on safety and efficacy.

Adults and the elderly

Monofer can be administered either as an intravenous bolus injection, as an intravenous drip infusion or as a direct injection into the venous limb of the dialyser.

Monofer should not be administered concomitantly with oral iron preparations, since the absorption of oral iron might be decreased (see section 4.5).

Intravenous bolus injection

Monofer may be administered as an intravenous bolus injection up to 500 mg up to three times a week at an administration rate of up to 250 mg iron/minute. It may be administered undiluted or diluted in maximum 20 ml sterile 0.9% sodium chloride.

Intravenous drip infusion

The cumulative iron dose required may be administered in a single Monofer infusion up to 20 mg iron/kg body weight or as weekly infusions until the cumulative iron dose has been administered.

If the cumulative iron dose exceeds 20 mg iron/kg body weight, the dose must be split in two administrations with an interval of at least one week. It is recommended whenever possible to give 20 mg iron/kg body weight in the first administration. Dependent on clinical judgement the second administration could await follow-up laboratory tests.

Doses up to 1000 mg must be administered over more than 15 minutes.

Doses exceeding 1000 mg must be administered over 30 minutes or more.

Monofer should be added to maximum 500 ml sterile 0.9% sodium chloride. Please refer to section 6.3 and 6.6.

Injection into dialyser

Monofer may be administered during a haemodialysis session directly into the venous limb of the dialyser under the same procedures as outlined for intravenous bolus injection.

The iron(III) isomaltoside 1000 in Monofer has a low toxicity. The preparation is well tolerated and has a minimal risk of accidental overdosing.

Overdose may lead to accumulation of iron in storage sites eventually leading to haemosiderosis. Monitoring of iron parameters such as serum ferritin may assist in recognising iron accumulation. Supportive measures such as chelating agents can be used.

Shelf life

Shelf life of ampoules as packaged for sale: 3 years.

Shelf life of vials as packaged for sale: 3 years.

Shelf life after first opening of the container (undiluted):

From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately.

If not used immediately, in-use storage times and conditions are the responsibility of the user.

Shelf life after dilution with sterile 0.9% sodium chloride:

Chemical and physical in-use stability has been demonstrated for 48 hours at 30°C in dilutions up to 1:250 with sterile 0.9% sodium chloride.

From a microbiological point of view, the product should be used immediately.

This medicinal product does not require any special storage conditions.

For storage conditions of the reconstituted and diluted solution, see section 6.3.

Type 1 glass ampoule.

Pack sizes: 5 × 1 ml, 10 × 1 ml, 5 × 2 ml, 10 × 2 ml, 2 × 5 ml, 5 × 5 ml, 2 × 10 ml, 5 × 10 ml

Type 1 glass vial with chlorobutyle rubber stopper and aluminium cap.

Pack sizes: 1 × 1 ml, 5 × 1 ml, 10 × 1 ml, 5 × 2 ml, 10 × 2 ml, 1 × 5 ml, 2 × 5 ml, 5 × 5 ml, 1 × 10 ml, 2 × 10 ml, 5 × 10 ml

Not all pack sizes may be marketed.

Inspect vials/ampoules visually for sediment and damage before use. Use only those containing sediment-free, homogeneous solution.

Monofer is for single use only and any unused solution should be disposed of in accordance with local requirements.

Monofer must only be mixed with sterile 0.9% sodium chloride. No other intravenous dilution solutions should be used. No other therapeutic agents should be added. For dilution instructions, see section 4.2.

The reconstituted solution for injection should be visually inspected prior to use. Use only clear solutions without sediment.