Iron Isomaltoside

 

•       Chronic Kidney Disease - functional iron deficiency should be corrected before ESA therapy, management of anaemia

•       Antenatal and postpartum – haemorrhage, delayed wound healing, reduced quality and quantity of lactation

•       Gastroenterology - Inflammatory (Crohn’s & colitis), acute/chronic blood loss

•       Pre- and post-operative – rapid increase in Hb levels & alternate to blood transfusion

•       Gynecology Oncology – improved response to erythropoietic proteins

•       Chronic Heart Failure – reduced left ventricle ejection fraction, improved functional capacity, low side effect

•       ITU, care of the elderly, palliative care – rapid increase in Hb levels & alternate to blood transfusion

In General:

• Requirement of rapid iron replacement
• Ongoing occult blood loss
• May delay investigative procedures
• Interactions with many common oral drugs

 

 May be inadequate during ESA therapy

Accelerated erythropoiesis can increase demand for iron beyond the amount supplied orally

Gastrointestinal adverse events

• Can affect over 50% of patients
• Can adversely affect nutritional intake
• Improved if iron tablets are taken with food, but this decreases absorption

Compliance

• Pill burden: usually 2 or 3 tablets per day
• Affected by gastrointestinal intolerance

Oxidative stress

• High oral iron doses can saturate the iron transport system if the iron is rapidly released, resulting in oxidative stress

When parental iron

•      Indicated for the treatment of iron deficiency when oral iron preparations are ineffective or cannot be used

•      Comparative clinical trials show a faster and more prolonged response with IV iron than with oral iron

•      IV iron is more effective, better tolerated and improves the quality of life to a greater extent than oral iron

•      Concerns regarding allergic reactions

Why Iron Isomaltoside?

•       very low immunogenic potential and a very low content of labile and free iron and therefore less oxidative stress and potentially better long-term safety

•       enables to be administered as a rapid high dose infusion in doses exceeding 1000 mg without the application of a test dose

•       offers a considerable dose flexibility, including the possibility of providing full iron repletion in a single infusion (one-dose iron repletion)

•       consists of iron and a carbohydrate moiety where the iron is tightly bound in a matrix structure

•       enables a controlled slow release of bioavailable iron to the iron-binding proteins, with potentially a reduced risk of free iron toxicity

Pharmacodynamic properties

•       Iron Isomaltoside solution for injection is a colloid with strongly bound iron in spheroidal iron-carbohydrate particles

•       The formulation contains iron in a complex that enables a controlled and slow release of bioavailable iron to iron-binding proteins with little risk of free iron

•       Each particle consists of a matrix of iron(III) atoms and isomaltoside pentamers – the chelation of iron(III) with carbohydrate confers to the particles a structure resembling ferritin that is suggested to protect against the toxicity of unbound inorganic iron(III)

•       The iron is available in a non-ionic water-soluble form in an aqueous solution with pH between 5.0 and 7.0

•       Evidence of a therapeutic response can be seen within a few days of administration as an increase in the reticulocyte count. Due to the slow release of bioavailable iron serum ferritin peaks within days after an intravenous dose and slowly returns to baseline after weeks

 

Pharmacodynamic properties (cont.)

•       Following IV administration, Iron Isomaltoside 1000 is rapidly taken up by the cells in the reticuloendothelial system (RES), particularly in the liver and spleen, from where iron is slowly released

•       The plasma half-life is 5 hr for unbound circulating iron and 20 hr for total iron (bound and circulating)

•       Circulating iron is removed from the plasma by cells of the reticuloendothelial system which split the complex into its components of iron and isomaltoside 1000

•       The iron is immediately bound to the available protein moieties to form haemosiderin or ferritin, the physiological storage forms of iron, or to a lesser extent, to the transport molecule transferrin

•       Due to the size of the carbohydrate–iron complex, intact Iron Isomaltoside 1000 is not eliminated via the kidneys

•       Small quantities of iron are eliminated in urine and faeces

•       The carbohydrate component, isomaltoside 1000, is either metabolized or excreted

Why Ideal IV..?

•       Capable of delivering a wide dosing range to allow a single visit iron correction dose

•       Test dose not necessary

•       Controlled slow release of bioavailable iron to the iron-binding proteins, with potentially a reduced risk of free iron toxicity

•       A fast infusion, and minimal potential side effects including low catalytic/labile iron release and negligible risk of anaphylaxis

•       They should be convenient for the patient and the health care professional

•       Cost effective for the health care system

•       Each 1 ml contains 100 mg iron

Snapshot

•       Tightly bind iron – more doses in one shot

•       Each 1 ml contains 100 mg iron

•       Test dose not necessary

•       One dose Iron Repletion

•       No ceiling in dose (upto 2000 mg can be given in 1 shot and 3000 mg in cumulative dose)

•       Can be administered as a single infusion in 30-60 minutes for doses upto 20mg iron/kg body weight

•       Negligible Hypophosphatemia Episode

•       An important component of the strategy as an alternative to blood transfusion