Ferric Derisomaltose

Registered South African indications:

• Iron deficiency
  - When oral iron preparations are ineffective or cannot be used
  - Where there is a clinical need to deliver iron rapidly

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Known serious hypersensitivity to other parenteral iron products
• Non-iron deficiency anaemia (e.g. haemolytic anaemia)
• Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis)
• Ferric derisomaltose should not be used in patients with ongoing bacteraemia

South African recommendations

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Acute or chronic infection

Hypersensitivity reactions

• Parenterally administered iron preparations such as ferric derisomaltose can cause hypersensitivity reactions, including serious and potentially fatal anaphylactic/anaphylactoid reactions
• Reactions have also been reported after previously uneventful doses of other parenteral iron complexes
• Risk is increased in patients with known allergies, including medicine allergies, and in those with a history of severe asthma, eczema, or other atopic allergies
• There is also an increased risk in patients with immune or inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis)
• Ferric derisomaltose should only be administered by staff trained to evaluate and manage anaphylactic reactions, in an environment where full resuscitation facilities are available
• Patients should be observed for adverse effects for at least 30 minutes following each injection
• If hypersensitivity reactions or signs of intolerance occur during administration, treatment must be stopped immediately
• Facilities for cardio-respiratory resuscitation should be available, including injectable 1:1000 epinephrine (adrenaline); additional treatment with antihistamines and/or corticosteroids may be required

Hepatic impairment

• Monofer should only be administered after careful benefit/risk assessment in patients with liver impairment
• Avoid use in patients with hepatic impairment (alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) > 3 times upper limit of normal) where iron overload is a precipitating factor, particularly in Porphyria Cutanea Tarda

Forms avail. in SA and covered in this monograph: inj

South African registered indications and dosages

Iron deficiency
- When oral iron preparations are ineffective
- When there is a clinical need to deliver iron rapidly

Iron replacement in patients with iron deficiency: The cumulative iron dose is calculated for each patient individually (see table below or use the Ganzoni formula)

• IV Bolus Injection: Admin. up to 500mg, up to three times per week; Rate of admin. should not exceed 250mg of iron/min
• IV Drip Infusion: Total required iron dose (up to 20mg/kg body weight) can be admin. as a single infusion; Alternatively, the dose can be divided into weekly infusions until the total cumulative dose is administered; Infusion Time: Doses up to 1000mg (1g) must be given over at least 15 min; Doses exceeding 1000mg (1g) must be given over at least 30 min

Simplified table: Iron need

Hb (g/dL)	Patients with bodyweight  50kg to < 70kg	Patients with bodyweight  ≥ 70kg
≥ 10	1000mg	1500mg
< 10	1500mg	2000mg

Iron replacement for blood loss: Supply an amount of iron equivalent to the amount of iron represented in the blood loss

• IV: If the Hb level is reduced: Use the Ganzoni formula considering that the depot iron does not need to be restored (see additional prescribing points)
• IV: If the volume of blood lost is known: The administration of 200mg 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

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Ferric derisomaltose 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 administration

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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

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The Ganzoni formula is recommended in patients who are likely to require individually adjusted dosing such as patients with anorexia nervosa, cachexia, obesity, pregnancy or anaemia due to bleeding (See additional prescribing points)

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

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Method of administration
Intravenous bolus injection: May be administered undiluted or diluted in maximum 20ml sterile 0.9% sodium chloride
Intravenous drip infusion: Should be added to maximum 500ml sterile 0.9% sodium chloride (refer to product specific information)
Injection into dialyser: 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

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Caution; not recommended
• There is only limited data from the use of ferric derisomaltose in pregnant women from one study with 100 exposed women
• A careful risk/benefit evaluation is required before use during pregnancy and ferric derisomaltose should not be used during pregnancy unless clearly necessary
• Iron deficiency anaemia occurring in the first trimester of pregnancy can in most cases be treated with oral iron
• Treatment should be confined to the second and third trimester if the benefit is judged to outweigh the potential risk for both the mother and the foetus
• Foetal bradycardia may occur following administration of parenteral irons. It is usually transient and a consequence of a hypersensitivity reaction in the mother

Breastfeeding

South African recommendations

• Caution; not recommended
• A clinical study showed that transfer of iron from ferric derisomaltose to human milk was very low. At therapeutic doses, no effects on the breastfeed newborns/infants are anticipated
• Women using ferric derisomaltose should not breastfeed their infants

Fertility

South African recommendations

• There are no data on the effect of ferric derisomaltose on human fertility. Fertility was unaffected following treatment in animal studies

South African recommendations

• Caution; no information available

South African recommendations

• Caution; not recommended
  In patients with liver impairment, ferric derisomaltose should only be administered after careful benefit/risk assessment. Administration should be avoided in patients with hepatic impairment

South African recommendations

• Caution; no information available

Immune, Blood and Lymphatic System Disorders

Uncommon

• Hypersensitivity, including severe reactions

Rare

• Anaphylactoid reactions
• Anaphylactic reactions

Nervous System Disorders

Uncommon

• Headache
• Paraesthesia
• Dysgeusia
• Loss of consciousness
• Dizziness
• Fatigue

Rare

• Dysphonia
• Seizure
• Tremor
• Altered mental status

Cardiac Disorders

Uncommon

• Tachycardia

Rare

• Arrhythmia

Vascular Disorders

Uncommon

• Hypotension
• Hypertension

Respiratory Disorders

Uncommon

• Chest pain
• Dyspnoea
• Bronchospasm

Gastrointestinal Disorders

Common

• Nausea

Uncommon

• Abdominal pain
• Vomiting
• Dyspepsia
• Constipation
• Diarrhoea

Skin and Subcutaneous Tissue Disorders

Common

• Rash

Uncommon

• Pruritus
• Urticaria
• Flushing
• Sweating
• Dermatitis

Rare

• Angioedema

Not known

• Distant skin discolouration

Metabolism and Nutrition Disorders

Uncommon

• Hypophosphataemia

Musculoskeletal Disorders

Uncommon

• Back pain
• Myalgia
• Arthralgia
• Muscle spasms

General Disorders and Administration Site Conditions

Common

• Injection site reactions
  • Injection site erythema
  • Swelling
  • Discomfort
  • Burning
  • Pain
  • Bruising
  • Discolouration
  • Pigmentation
  • Extravasation
  • Irritation
  • Reaction

Uncommon

• Pyrexia
• Chills/shivering
• Infection
• Local phlebitic reaction
• Skin exfoliation

Rare

• Malaise
• Influenza like illness

Investigations

Uncommon

• Increased hepatic enzymes

Sensory Disorders

Uncommon

• Blurred vision

• Oral iron therapy
  (See additional prescribing points)

• Full blood count
• Serum ferritin

Coadministration with oral iron

• The absorption of oral iron is reduced when administered concomitantly with Monofer. Oral iron therapy should not be started earlier than 5 days after the last injection of ferric derisomaltose

Ganzoni formula

Iron need [mg iron] = Body weight^(A) [kg] x (Target Hb^(E) [g/dl] - Actual Hb)^(B) [g/dl] x 2.4^(C) + Iron for iron stores^(D) [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 x 0,07 x 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 and others 1000 mg iron as stores
• (E) Default Hb target is 15 g/dl in the Ganzoni formula. In special cases such as pregnancy consider using a lower haemoglobin target

Ferric derisomaltose solution for injection is a colloid with strongly bound iron in spheroidal iron-carbohydrate particles. The complex forms a stable matrix type structure with about 10 iron(III) atoms to one molecule of isomaltoside pentamer with the iron(III) bound in cavities of the 3-D structure of isomaltoside pentamers.

Injection (per 5ml) 500mg

• Monofer (Pharmaplan) originator

Injection (per 10ml) 1000mg

• Monofer (Pharmaplan) originator