Usage
Deferiprone is an iron chelator indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. It is also used for transfusional iron overload due to other chronic anemias like sickle cell disease. It is important to remove excess iron because high levels can lead to health problems such as heart failure, liver disease, diabetes, and delayed growth in children. Deferiprone works by binding to iron, which helps the body eliminate it through urine.
Alternate Names
The active ingredient is sometimes referred to as 3-hydroxy-1,2-dimethylpyridin-4-one. A common brand name is Ferriprox.
How It Works
Pharmacodynamics: Deferiprone acts as an iron chelator, binding to ferric iron (Fe3+) in a 3:1 molar ratio (deferiprone:iron). This neutral complex is then excreted primarily in the urine.
Pharmacokinetics:
- Absorption: Deferiprone is rapidly absorbed after oral administration, with peak plasma concentration achieved within 1 hour on an empty stomach. Food may decrease the rate, but not the extent of absorption.
- Metabolism: It is extensively metabolized in the liver, mainly through glucuronidation by the UGT1A6 enzyme, forming the inactive metabolite deferiprone 3-O-glucuronide (DFP-G).
- Elimination: More than 90% of free deferiprone is eliminated from plasma within 5-6 hours. Both deferiprone and DFP-G are primarily excreted in the urine.
Dosage
Standard Dosage
Adults:
- Initial dose: 25 mg/kg body weight orally three times a day (total daily dose: 75 mg/kg).
- Maximum dose: 33 mg/kg orally three times a day (total daily dose: 99 mg/kg).
Children:
- Tablets (≥8 years old): Same as adult dosing.
- Oral Solution (≥3 years old): Same as adult dosing, with adjustments for different formulations.
- Children under 3 years old: Dosage must be determined by a doctor.
Special Cases:
- Elderly patients: Dose selection should be cautious, usually starting at the low end of the dosing range.
- Patients with Renal Impairment: No dose adjustment is necessary for mild to severe impairment. Limited data for end-stage renal disease.
- Patients with Hepatic Dysfunction: No dose adjustment is needed for mild or moderate hepatic impairment. Caution advised, with close liver enzyme monitoring. Limited information available for severe hepatic impairment.
- Patients with Comorbid Conditions: Caution should be exercised in patients with other medical conditions. Monitor for drug interactions.
Clinical Use Cases
Deferiprone is not specifically indicated for use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use remains iron chelation in chronic conditions.
Dosage Adjustments
Dose adjustments may be needed based on patient response, serum ferritin levels, and therapeutic goals. If serum ferritin falls consistently below 500 mcg/L, temporary treatment interruption may be considered.
Side Effects
Common Side Effects
Nausea, vomiting, abdominal pain, arthralgia, chromaturia (change in urine color), neutropenia.
Rare but Serious Side Effects
Agranulocytosis, neutropenia, liver injury (increased ALT levels).
Long-Term Effects
Chronic complications from prolonged use are possible, including zinc deficiency and other metabolic imbalances.
Adverse Drug Reactions (ADR)
Agranulocytosis requires immediate intervention. Neutropenia can also be an ADR requiring close monitoring.
Contraindications
Hypersensitivity to deferiprone, history of recurrent episodes of neutropenia, history of agranulocytosis, pregnancy, breastfeeding.
Drug Interactions
Avoid coadministration with other drugs known to cause neutropenia or agranulocytosis. Allow at least a 4-hour interval between deferiprone and mineral supplements or antacids containing polyvalent cations (e.g., iron, aluminum, zinc) to prevent binding and malabsorption of supplements. Avoid concomitant use of UGT1A6 inhibitors (e.g., diclofenac, probenecid, silymarin).
Pregnancy and Breastfeeding
Deferiprone is contraindicated during pregnancy (Pregnancy Category D) and breastfeeding. It may cause fetal harm. Safer alternatives should be considered.
Drug Profile Summary
- Mechanism of Action: Iron chelator, binds to ferric iron, forming a complex that is excreted in urine.
- Side Effects: Nausea, abdominal pain, arthralgia, neutropenia, agranulocytosis.
- Contraindications: Hypersensitivity, history of neutropenia/agranulocytosis, pregnancy, breastfeeding.
- Drug Interactions: Drugs that cause neutropenia/agranulocytosis, UGT1A6 inhibitors, polyvalent cations.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 25-33 mg/kg three times daily, max 99 mg/kg/day. Adjust based on response and serum ferritin.
- Monitoring Parameters: Absolute neutrophil count (ANC) weekly, serum ferritin every 2-3 months, liver enzymes, zinc levels.
Popular Combinations
Combination therapy with deferoxamine is sometimes used when monotherapy is insufficient, or when rapid iron chelation is needed.
Precautions
- Monitor ANC weekly, especially initially.
- Monitor serum ferritin, liver enzymes, and zinc levels.
- Patient education about signs of infection.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Deferiprone?
A: The initial dose is 25 mg/kg orally three times daily, with a maximum dose of 99 mg/kg/day. Adjustments are made based on patient response and ferritin levels.
Q2: What is the mechanism of action of Deferiprone?
A: Deferiprone chelates iron by binding to ferric iron (Fe3+), creating a complex that is then excreted in the urine.
Q3: What are the most serious side effects of Deferiprone?
A: Agranulocytosis and neutropenia are the most serious, potentially life-threatening side effects.
Q4: Can Deferiprone be used during pregnancy?
A: No, Deferiprone is contraindicated during pregnancy due to the risk of fetal harm.
Q5: What are the key monitoring parameters for patients on Deferiprone?
A: Weekly ANC, serum ferritin levels every 2-3 months, liver enzyme levels, zinc levels.
Q6: How should Deferiprone be administered?
A: Orally, three times a day, with or without food (food may reduce nausea).
Q7: What should patients be advised to do if they develop an infection while on Deferiprone?
A: Immediately report the infection to their physician and interrupt therapy until the infection resolves and ANC recovers.
Q8: What should be done if a patient’s serum ferritin falls below 500 mcg/L consistently?
A: Temporary interruption of therapy should be considered.
Q9: Can Deferiprone be used in patients with renal impairment?
A: Yes, usually without dose adjustment, but with caution and monitoring.
Q10: Are there any specific drug interactions to be aware of with Deferiprone?
A: Yes, avoid concurrent use of drugs causing neutropenia/agranulocytosis, UGT1A6 inhibitors, and agents containing polyvalent cations (iron, aluminum, zinc). Separate administration by at least 4 hours.
