Ferric Derisomaltose

Approved Indications:

• Treatment of iron deficiency anemia (IDA) in adults when oral iron preparations are ineffective or cannot be used.
• Iron deficiency requiring rapid iron repletion.
• Iron deficiency anemia associated with chronic kidney disease (CKD), including non-dialysis and dialysis patients.
• Iron deficiency anemia due to blood loss, malabsorption, or chronic inflammatory diseases such as inflammatory bowel disease (IBD).
• Correction of iron deficiency prior to elective surgery to reduce the need for transfusions.

Off-label/Clinically accepted uses:

• Iron deficiency anemia in patients with heart failure and other chronic conditions.
• Iron deficiency related to cancer therapy.

• Route: Intravenous (IV) administration only.
• Dose:
• Single doses up to 1,000 mg elemental iron can be administered per infusion.
• Total cumulative dose is based on calculated iron deficit, typically using Ganzoni’s formula or clinical judgment.
• Frequency:
• Repeat dosing can be given at weekly intervals if total iron requirement exceeds single dose limit.
• Special populations:
• Renal impairment: No dose adjustment required.
• Hepatic impairment: Use cautiously; avoid in severe liver dysfunction.
• Elderly: No specific adjustment; monitor response.
• Administration:
• Undiluted IV injection over 20 minutes or diluted in 100–250 mL normal saline and infused over 15–30 minutes.
• Monitor for hypersensitivity during and for at least 30 minutes after infusion.

Ferric Derisomaltose is a stable complex of ferric iron with derisomaltose carbohydrate, designed for intravenous iron delivery. Upon administration, the complex is taken up by macrophages in the reticuloendothelial system, where it is broken down to release elemental iron. This iron is then bound to transferrin in plasma and transported to the bone marrow to support erythropoiesis, restoring hemoglobin levels. The stability of the iron-carbohydrate complex minimizes free iron release, reducing oxidative damage and allowing administration of high doses safely.

• Absorption: Not applicable (administered intravenously).
• Distribution: Rapidly taken up by the reticuloendothelial system (liver, spleen, bone marrow).
• Metabolism: The iron complex is metabolized intracellularly in macrophages; elemental iron is released gradually.
• Elimination: Iron is incorporated into body stores or used in hemoglobin synthesis; the carbohydrate moiety is cleared renally.
• Half-life: Terminal elimination half-life ~20 hours.
• Onset of effect: Clinical response in hemoglobin levels is usually evident within 1 to 2 weeks post-infusion.
• Bioavailability: 100% (IV route).

• Pregnancy: No well-controlled studies in pregnant women; use only if clearly needed. Animal studies do not show teratogenicity but caution advised.
• Lactation: Limited data on excretion into breast milk. Presumed low exposure; use with caution during breastfeeding.

• Primary class: Parenteral iron supplement
• Subclass: Intravenous iron carbohydrate complex (non-dextran)

• Known hypersensitivity to ferric derisomaltose or any excipients.
• Evidence of iron overload or disturbances in iron metabolism (e.g., hemochromatosis).
• Anemia not due to iron deficiency.
• First trimester of pregnancy, unless benefits outweigh risks.
• Active systemic infections.

• Hypersensitivity: Risk of anaphylaxis and serious hypersensitivity reactions. Monitor closely during and after infusion.
• Hypophosphatemia: May cause symptomatic hypophosphatemia; monitor phosphate levels in high-risk patients.
• Iron overload: Avoid repeated administration without confirmed iron deficiency.
• Infections: Iron can promote bacterial growth; avoid during acute infections.
• Liver impairment: Use cautiously in patients with significant hepatic dysfunction.
• Blood pressure: Transient hypertension or hypotension may occur during infusion.
• Clinical monitoring: Regular monitoring of hemoglobin, ferritin, TSAT, phosphate, and signs of allergic reactions is recommended.

Common:

• Nausea, headache, dizziness
• Injection site reactions (pain, swelling, erythema)
• Arthralgia and myalgia
• Hypotension or hypertension during infusion

Serious but rare:

• Anaphylactic or anaphylactoid reactions
• Severe hypersensitivity
• Symptomatic hypophosphatemia (muscle weakness, fatigue)

Onset & dose-dependence:

• Most adverse effects occur during or shortly after infusion.
• Hypophosphatemia may develop after repeated dosing.

• Oral iron supplements: Concurrent use may cause iron overload; avoid.
• Phosphate binders: Increased risk of hypophosphatemia.
• ACE inhibitors and ARBs: Possible increased risk of hypotension during infusion.
• CYP450 enzymes: No significant interactions; not metabolized by hepatic enzymes.

• Increased emphasis on monitoring phosphate levels due to risk of hypophosphatemia.
• Guidelines from kidney disease and cardiology societies recommend IV iron (including ferric derisomaltose) for iron deficiency anemia when oral iron is inadequate or contraindicated.
• Safety updates stress caution in patients with severe liver disease and during pregnancy.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Protect from light.
• Do not freeze.
• Use immediately after opening.
• If diluted for infusion, use within 12 hours at room temperature.
• Vials and pre-filled syringes are for single use only.