How to bind iron, specifically referring to Iron (Fe) binding?

From the Guidelines

To bind iron, use deferasirox (Exjade, Jadenu) as the first-line treatment, given its oral administration and once-daily dosing at 20-40 mg/kg. Deferasirox is a tridentate lipophilic oral chelating agent that selectively binds to iron in a 2:1 molar ratio and mobilizes iron from stores 1. The goal of chelation therapy is to detoxify those organs containing excess iron by binding the iron, removing it, and then excreting the compound in urine and bile. Other options include deferiprone (Ferriprox), taken three times daily at 75-100 mg/kg/day, and deferoxamine (Desferal), which requires subcutaneous or intravenous administration at 20-60 mg/kg/day for 8-24 hours. These medications work by forming complexes with iron molecules, allowing excess iron to be excreted through urine or stool. Iron chelation therapy is primarily used for conditions involving iron overload, such as hemochromatosis, thalassemia, or multiple blood transfusions.

• Side effects may include gastrointestinal disturbances, skin rash, and kidney or liver function changes, so regular monitoring is essential, including tests of renal and hepatic function 1.
• Treatment duration depends on the severity of iron overload and is typically guided by serum ferritin levels or other iron markers, with the goal of decreasing ferritin levels to less than 1000 mcg/L 1.
• Always consult a healthcare provider before starting iron chelation therapy, as inappropriate use can lead to iron deficiency or other complications.
• Monitoring serum ferritin may be useful to assess iron overload, although it has limitations due to the influence of infection, acute and chronic inflammation, and alcohol abuse 1.

From the FDA Drug Label

Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Deferiprone is a chelating agent with an affinity for ferric ions (iron III). Deferiprone binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable at physiological pH.

To bind iron, deferasirox and deferiprone can be used as they are both iron chelators.

• Deferasirox binds iron in a 2:1 ratio.
• Deferiprone binds iron in a 3:1 ratio. 2 3

From the Research

Iron Chelation Therapy

To bind iron, several iron chelation therapies are available, including:

• Desferrioxamine mesylate (desferrioxamine) 4
• Deferiprone (DFP) 4, 5, 6, 7
• Deferasirox (DFX) 4, 5, 6, 8

Mechanism of Action

These therapies work by:

• Binding to iron in the body and removing it through excretion 4, 5, 6, 7, 8
• Reducing iron absorption in the gut 8
• Preventing iron toxicity in organs such as the heart and liver 4, 5, 6, 7, 8

Efficacy and Safety

Studies have shown that:

• Desferrioxamine is effective in reducing iron overload, but its use is limited by the need for subcutaneous infusion 4
• Deferiprone and deferasirox are oral iron chelators that are effective in reducing iron overload, with deferiprone showing non-inferiority to desferrioxamine in some studies 5, 7
• The combination of deferiprone and deferasirox is efficacious in iron overloaded patients with β-thalassemia major 6
• Deferasirox offers an important treatment option for people with thalassaemia and secondary iron overload, but its efficacy and safety compared to desferrioxamine are still being studied 5

Adverse Events

Common adverse events associated with these therapies include:

• Gastrointestinal symptoms such as nausea, vomiting, and abdominal pain 5, 6, 7
• Joint pain and arthralgia 5, 6, 7
• Increases in liver enzymes and renal impairment 4, 5, 7
• Neutropenia and agranulocytosis 7