DEFERIPRONE KEY

Indications

• Transfusion-related chronic iron overload in patients with beta thalassaemia major receiving infrequent blood transfusions
• Chronic iron overload in patients where desferrioxamine is contraindicated or inadequate
• Other anaemias requiring treatment of iron overload (specialist use only)

Dosage

Children: Initially 7–21 mg/kg once daily for children aged 2–17 years, with dose adjustments based on serum-ferritin concentration and the amount of transfused blood, and a maximum of 28 mg/kg per day.

Adults: Initially 7–21 mg/kg once daily, adjusted according to serum-ferritin concentration and the amount of transfused blood, with a maximum of 21 mg/kg per day.

Mechanism of action

Deferiprone is an iron chelator that binds to ferric ions (iron III) and forms a 3:1 (deferiprone:iron) stable complex, which is then eliminated in the urine. It has a higher selectivity for iron compared to other metals such as zinc, copper, and aluminum, making it effective in reducing iron overload.

Pharmacodynamics

Deferiprone decreases iron loading in various tissues by chelating excess iron, which can prevent oxidative stress and subsequent damage to organs such as the heart and liver. Its capacity to form stable complexes with ferric ions leads to enhanced urinary excretion of iron, thereby lowering total body iron levels.

Pharmacokinetics

Deferiprone is absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1 to 2 hours after oral administration. It is metabolized primarily in the liver, with an elimination half-life of about 2 to 3 hours. The majority of the drug is excreted in the urine as chelated iron complexes, while a smaller proportion is excreted unchanged.

Contra-indications

• Hypersensitivity to deferiprone or any of its components
• Severe renal impairment
• History of myelodysplastic syndromes
• Platelet count less than 50 x 10^9/litre

Adverse effects

• Gastrointestinal discomfort
• Constipation
• Diarrhoea
• Nausea
• Vomiting
• Headache
• Skin reactions
• Urine abnormalities
• Anxiety
• Cataract
• Cholelithiasis
• Dizziness
• Acute kidney injury

Interactions

• Ascorbic acid may increase the risk of cardiovascular adverse effects when used with deferiprone
• Oral iron may decrease absorption of deferiprone
• NSAIDs may increase exposure to deferiprone
• Diclofenac may increase exposure to deferiprone
• Oral zinc may decrease absorption of deferiprone

Precautions

• Monitor liver function before treatment initiation and periodically during therapy
• Monitor renal function, including proteinuria, before treatment initiation and during therapy
• Regular eye and ear examinations before treatment and annually during treatment
• Increased risk of side effects in elderly patients

Pregnancy

There are limited data on the use of deferiprone in pregnant women. Use only if clearly needed and the benefits outweigh the risks.

Breast-feeding

It is unknown if deferiprone is excreted in human breast milk. Caution is advised when administering to breastfeeding women.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Film-coated tablets
• Deferiprone 180 mg tablets

Mechanism of action

Deferiprone is an iron chelator that binds to ferric ions (iron III) and forms a 3:1 (deferiprone:iron) stable complex and is then eliminated in the urine. Deferiprone is more selective for iron in which other metals such as zinc, copper, and aluminum have a lower affinity for deferiprone. Deferiprone is a chelating agent with an affinity for ferric ion (iron III). Deferiprone binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable over a wide range of pH values. Deferiprone has a lower binding affinity for other metals such as copper, aluminum and zinc than for iron.