4.1 Dosing Considerations
- The dose of MONOFERRIC (ferric derisomaltose for injection) is expressed in terms of mg of elemental iron, with each mL of undiluted MONOFERRIC containing 100 mg of elemental iron.
- The patient’s total body iron deficit (cumulative amount of iron needed to replete body iron stores and correct IDA) is not the same as the allowable iron dose per infusion which is limited to 20 mg iron/kg body weight with MONOFERRIC. The optimal hemoglobin (Hb) target level and iron stores may vary in different patient groups and between patients. Iron deficiency anemia will not appear until essentially all iron stores have been depleted. Iron therapy should therefore replenish both hemoglobin iron and iron stores.
4.2 Recommended Dose and Dosage Adjustment
- The iron dose and administration schedule for MONOFERRIC must be individually established for each patient, with allowance for clinical judgement. Clinicians may choose between calculating the cumulative dose for iron repletion based on patient’s Hb and body weight based on the Simplified Table or Ganzoni formula, or treating with a fixed dose (repeated dose might be needed if the patient requires further iron repletion).
1. Treatment approach based on calculating total body iron deficit
The posology of MONOFERRIC can follow a stepwise approach:  determination of the individual iron need  calculation and administration of the iron dose(s),  post-iron repletion assessments.
Step 1: Determination of the iron need:
The cumulative iron need can be determined using either the Simplified Table (i) or the Ganzoni formula below (ii). In the clinical studies with CKD patients, the Ganzoni formula was used and in the clinical study with IDA patients of various causes other than CKD, the Simplified table was used.
The iron need is expressed in mg elemental iron.
i. Simplified Table:
|Hb (g/dL)||Patients with|
bodyweight <50 kg
|Patients with bodyweight|
50 kg to <70 kg
|Patients with bodyweight|
|≥10||500 mg||1000 mg||1500 mg|
|<10||500 mg||1500 mg||2000 mg|
ii. Ganzoni formula:
|=||Body weight(A)||x||(Target Hb(D) – Actual Hb)(B)||x||2.4||+||Iron for iron stores(C)|
|[mg iron]||[kg]||[g/dl]||[mg iron]|
Step 2: Calculation and administration of the maximum individual iron dose(s):
Based on the iron need determined above the appropriate dose(s) of MONOFERRIC should be administered taking into consideration the following:
A single MONOFERRIC infusion should not exceed 20 mg iron/kg body weight. Single doses above 1500 mg are not recommended.
Step 3: Post-iron repletion assessments:
Re-assessment should be performed by the clinician based on the individual patient's condition. The Hb level should be re-assessed no earlier than 4 weeks post final MONOFERRIC administration to allow adequate time for erythropoiesis and iron utilisation. In the event the patient requires further iron repletion, the iron need should be recalculated.
2. Fixed dose approach
For both NDD-CKD patients and patients of various causes other than CKD with IDA receiving an IV infusion weighing more than 50 kg, a fixed dose of 1000 mg can be given, and the patient is re-evaluated for further iron need. Re-assessment should be performed by the clinician based on the individual patient's condition. The Hb level should be re-assessed no earlier than 4 weeks post MONOFERRIC administration to allow adequate time for erythropoiesis and iron utilisation. For patients weighing less than 50 kg, MONOFERRIC should be administered as 20 mg/kg actual body weight.
MONOFERRIC can be administered either as an intravenous drip infusion, as an intravenous bolus injection, or as a direct injection into the venous limb of the dialyzer.
Inspect vials visually for sediment and damage before use. Use only those containing sediment-free, homogeneous solution. The reconstituted solution for injection should be visually inspected prior to use. Use only clear solutions without sediment.
MONOFERRIC should only be administered when personnel trained to evaluate and manage anaphylactic reactions are immediately available, in an environment where full resuscitation facilities can be assured. Monitor patients carefully for signs and symptoms of hypersensitivity reactions during and following each administration of MONOFERRIC. The patient should be observed for adverse effects for at least 30 minutes following each MONOFERRIC administration (see 7 WARNINGS AND PRECAUTIONS, Immune, Hypersensitivity and Monitoring and Laboratory Tests).
Each IV iron administration is associated with a risk of a hypersensitivity reaction. Thus, to minimize risk the number of single IV iron administrations should be kept to a minimum.
Intravenous drip infusion:
The MONOFERRIC dose required may be administered in a single infusion up to 20 mg iron/kg body weight or as weekly infusions until the cumulative iron need has been addressed. Single doses above 1500 mg are not recommended.
If the cumulative iron need exceeds 20 mg iron/kg body weight, the dose must be split into 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.
|MONOFERRIC dose||Minimum administration time|
MONOFERRIC must only be diluted in sterile 0.9 % sodium chloride solution. For stability reasons, MONOFERRIC should not be diluted to concentrations less than 1 mg iron/mL (not including the volume of the ferric derisomaltose solution) and never diluted in more than 500 mL sterile 0.9 % sodium chloride. When diluting, there is no lower volume limit of 0.9 % sodium chloride solution.
Intravenous bolus injection:
MONOFERRIC may be administered as an intravenous bolus injection up to 500 mg up to once 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.
|Equivalent iron dose||Administration rate /|
|≤5 mL||≤500 mg||250 mg iron/minute||1 time a week|
Injection into dialyzer:
MONOFERRIC may be administered during a hemodialysis session directly into the venous limb of the dialyzer under the same procedures as outlined for intravenous bolus injection.