Deferiprone is a medication primarily used in the treatment of iron overload conditions such as thalassemia major and transfusional hemosiderosis. It belongs to a class of medications called iron chelators, which work by binding to excess iron in the body and helping its elimination through urine.

Iron overload can occur in individuals who require frequent blood transfusions, such as those with thalassemia or other chronic anemias. These transfusions can lead to an accumulation of iron in various organs, which can cause damage over time if not properly managed.

Deferiprone is typically administered orally and is often used in combination with other treatments for iron overload, such as deferoxamine. It is important for patients taking deferiprone to undergo regular monitoring of their iron levels and other relevant blood parameters to ensure the treatment is effective and safe.

Deferiprone (Ferriprox) is an oral iron-chelating agent that binds to plasma iron and helps it to pass in the urine. It is indicated in iron overload syndromes and patients with thalassemia.

Deferiprone (Ferriprox) Uses:

• Transfusional iron overload:
  • It is indicated for the treatment of iron overload resulting from repeated transfusions (in patients with thalassemia) who have an inadequate response to other iron-chelating agents.
• Limitation of use:
  • The efficacy and safety of the drug have not been established in other conditions of iron overload.

Deferiprone (Ferriprox) Dose in Adults

In the treatment of transfusional iron overload, the recommended initial oral dose of deferiprone is 25 mg/kg three times a day, which equates to a total daily dose of 75 mg/kg. The maximum dose is 33 mg/kg three times a day, totaling 99 mg/kg per day.

For example, for a person weighing 70 kg, the initial dose would be:

Initial dose = 25 mg/kg × 70 kg = 1750 mg per dose

Since we need to round the dose to the nearest 250 mg, this would be:

Initial dose ≈ 1750 mg ≈ 1750 mg (rounding to the nearest 250 mg)

So, the initial dose would be approximately 1750 mg per dose, three times a day.

And the maximum dose would be:

Maximum dose = 33 mg/kg × 70 kg = 2310 mg per dose

Rounding to the nearest 250 mg:

Maximum dose ≈ 2310 mg ≈ 2250 mg (rounding to the nearest 250 mg)

So, the maximum dose would be approximately 2250 mg per dose, three times a day.

It's important to note that these doses should be individualized based on the patient's response and therapeutic goals, and treatment may need to be temporarily interrupted if serum ferritin consistently falls below 500 mcg/L.

Deferiprone (Ferriprox) Dose in Children:

The safety and efficacy of the drug in children have not been established.

Pregnancy Risk Factor D

• Studies on animals have shown negative effects on reproduction with the use of deferiprone.
• While there's not much data on humans, it's possible that deferiprone might harm a developing fetus if taken during pregnancy.
• Therefore, women who could become pregnant should avoid getting pregnant while taking deferiprone.

Deferiprone use during breastfeeding:

• It's unclear whether deferiprone passes into breast milk.
• Because there's a chance it could cause serious problems for the nursing baby, the manufacturer suggests deciding whether to stop breastfeeding or stop taking the medication, considering how important the treatment is for the mother.

Ferriprox Dose in Kidney Disease:

The manufacturer's labeling for deferiprone does not include any specific dosage adjustments for individuals with renal impairment.

Ferriprox Dose in Liver disease:

• The manufacturer's labeling for deferiprone does not include any specific dosage adjustments for individuals with hepatic impairment.
• However, it's important to note that deferiprone has not been studied in patients with severe hepatic impairment.
• Therefore, caution should be exercised when administering deferiprone to patients with hepatic impairment, and close monitoring for potential adverse effects is recommended.

Common Side Effects of Deferiprone (Ferriprox):

• Gastrointestinal:
  • Nausea
• Genitourinary:
  • Urine discoloration

Less Common Side Effects of Deferiprone (Ferriprox):

• Central nervous system:
  • Headache
• Gastrointestinal:
  • Vomiting
  • Abdominal distress
  • Abdominal pain
  • Increased appetite
  • Diarrhea
  • Dyspepsia
  • Weight gain
  • Decreased appetite
• Hematologic & oncologic:
  • Neutropenia
  • Agranulocytosis
• Hepatic:
  • Increased serum ALT
  • Increased serum AST
• Neuromuscular and skeletal:
  • Arthralgia
  • Back pain
  • Limb pain
  • Arthropathy

Contraindications to Deferiprone (Ferriprox):

• In addition to hypersensitivity to deferiprone or any component of the formulation, Canadian labeling for deferiprone lists additional contraindications not found in US labeling.
• These include severe neutropenia (absolute neutrophil count <500/mm³), pregnancy, and breastfeeding.
• It's important for healthcare providers to be aware of these contraindications when considering deferiprone therapy for patients in Canada.

Warnings and Precautions

Agranulocytosis and Neutropenia: [US Boxed Warning]:

• Deferiprone carries a US Boxed Warning due to the risk of agranulocytosis, a condition characterized by a severe decrease in white blood cells, which can lead to serious infections, some of which may be fatal.
• Agranulocytosis may be preceded by neutropenia, so it's crucial to monitor the absolute neutrophil count (ANC) before starting treatment and weekly thereafter.
• If an infection develops, treatment should be interrupted, and ANC should be monitored more frequently.
• Patients should report any symptoms indicating infection promptly.
• If neutropenia (ANC <1,500/mm³) occurs, treatment should be interrupted, and other medications potentially associated with neutropenia should be withheld.
• Daily monitoring of complete blood count (CBC), white blood cell count corrected for nucleated red blood cells (corrected WBC), ANC, and platelets should be conducted until ANC recovery.
• Hospitalization may be necessary if ANC drops below 500/mm³, along with other clinically appropriate management.
• Treatment with deferiprone should not be resumed unless the potential benefits outweigh the risks.
• Neutropenia and agranulocytosis are generally reversible upon discontinuation of deferiprone.
• The mechanism for deferiprone-induced agranulocytosis is unknown, so concurrent use with other agents associated with neutropenia (or agranulocytosis) should be avoided.

Hepatotoxicity:

• Hepatotoxicity, characterized by elevated ALT (alanine aminotransferase) values, has been reported with the use of deferiprone.

Hypersensitivity:

• Hypersensitivity reactions, such as Henoch-Schönlein purpura (immunoglobulin A vasculitis), urticaria, and periorbital edema with skin rash, have been reported with the use of deferiprone.

Zinc deficiency:

• Deferiprone use has been associated with lower plasma zinc concentrations, which may lead to zinc deficiency.
• Healthcare providers should monitor zinc levels in patients receiving deferiprone and consider supplementation if necessary to maintain adequate zinc levels.
• This proactive approach helps prevent potential complications associated with zinc deficiency during deferiprone therapy.

Deferiprone: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
UGT1A6 Inhibitors	May increase the serum concentration of Deferiprone.
Risk Factor D (Consider therapy modification)
Polyvalent Cation Containing Products	May decrease the serum concentration of Deferiprone. Management: Separate administration of deferiprone and oral medications or supplements that contain polyvalent cations by at least 4 hours.
Risk Factor X (Avoid combination)
Myelosuppressive Agents	May enhance the neutropenic effect of Deferiprone.

Monitoring parameters:

• Serum Ferritin: Check every 2-3 months to monitor iron levels in the blood.
• Absolute Neutrophil Count (ANC):
  • Baseline: Check before starting treatment.
  • During Treatment: Monitor weekly.
  • If ANC drops below 1,500/mm³:
    • Monitor Complete Blood Count (CBC), White Blood Cell count (corrected for nucleated Red Blood Cells), ANC, and platelets daily until ANC recovers.
• Alanine Aminotransferase (ALT): Monitor monthly to detect liver function changes.
• Zinc Levels: Check periodically to monitor for potential zinc deficiency.
• Signs or Symptoms of Infection: Patients should report any signs or symptoms of infection promptly for appropriate evaluation and management.

How to administer Deferiprone (Ferriprox)?

• Timing: Take deferiprone in the morning, at midday, and in the evening for optimal effectiveness.
• With Food: Taking deferiprone with food may help decrease nausea.
• Avoid Polyvalent Cations: Administer deferiprone at least 4 hours apart from medications or supplements containing polyvalent cations such as iron, aluminum, or zinc to prevent interactions that may affect absorption.

Mechanism of action of Deferiprone (Ferriprox):

• Deferiprone is an iron-chelating agent that specifically targets ferric ions (iron III) in the body.
• It forms a complex with ferric ions in a ratio of 3:1 (deferiprone to iron), effectively binding to excess iron and facilitating its elimination through urine.
• While deferiprone primarily targets iron, it has a lower affinity for other metals such as copper, aluminum, and zinc, which means it is less likely to bind to these metals and interfere with their normal physiological functions.

Absorption:

• Rapid absorption into the bloodstream.

Distribution:

• In thalassemia patients, the distribution volume is approximately 1.6 liters per kilogram of body weight.

Protein Binding:

• Less than 10% of deferiprone is bound to proteins in the bloodstream.

Metabolism:

• The primary metabolic pathway is through UGT 1A6 enzymes. The major metabolite, 3-O-glucuronide, does not have iron-binding capacity.

Bioavailability:

• Both tablets and oral solutions have comparable bioavailability.

Half-Life Elimination:

• The half-life of deferiprone elimination is approximately 2 hours.

Time to Peak:

• Peak plasma concentrations are typically reached around 1 to 2 hours after administration.

Excretion:

• Deferiprone and its metabolites are primarily excreted in urine, accounting for 75% to 90% of the administered dose, with the majority being excreted as the metabolite.

International Brands of Deferiprone:

• Ferriprox
• Feripon
• Kelfer
• Neferi

Deferiprone Brand Names in Pakistan:

Deferiprone Tablets 500 mg
Ferinil	Global Pharmaceuticals
Ferriprox	Ici Pakistan Ltd.

 

Deferiprone Capsules 500 mg
Kelfer	A. J. Mirza Pharma (Pvt) Ltd

Deferiprone is a medication primarily used in the treatment of iron overload conditions such as thalassemia major and transfusional hemosiderosis. It belongs to a class of medications called iron chelators, which work by binding to excess iron in the body and helping its elimination through urine.

Iron overload can occur in individuals who require frequent blood transfusions, such as those with thalassemia or other chronic anemias. These transfusions can lead to an accumulation of iron in various organs, which can cause damage over time if not properly managed.

Deferiprone is typically administered orally and is often used in combination with other treatments for iron overload, such as deferoxamine. It is important for patients taking deferiprone to undergo regular monitoring of their iron levels and other relevant blood parameters to ensure the treatment is effective and safe.

Deferiprone (Ferriprox) is an oral iron-chelating agent that binds to plasma iron and helps it to pass in the urine. It is indicated in iron overload syndromes and patients with thalassemia.

Deferiprone (Ferriprox) Uses:

• Transfusional iron overload:
  • It is indicated for the treatment of iron overload resulting from repeated transfusions (in patients with thalassemia) who have an inadequate response to other iron-chelating agents.
• Limitation of use:
  • The efficacy and safety of the drug have not been established in other conditions of iron overload.

Deferiprone (Ferriprox) Dose in Adults

In the treatment of transfusional iron overload, the recommended initial oral dose of deferiprone is 25 mg/kg three times a day, which equates to a total daily dose of 75 mg/kg. The maximum dose is 33 mg/kg three times a day, totaling 99 mg/kg per day.

For example, for a person weighing 70 kg, the initial dose would be:

Initial dose = 25 mg/kg × 70 kg = 1750 mg per dose

Since we need to round the dose to the nearest 250 mg, this would be:

Initial dose ≈ 1750 mg ≈ 1750 mg (rounding to the nearest 250 mg)

So, the initial dose would be approximately 1750 mg per dose, three times a day.

And the maximum dose would be:

Maximum dose = 33 mg/kg × 70 kg = 2310 mg per dose

Rounding to the nearest 250 mg:

Maximum dose ≈ 2310 mg ≈ 2250 mg (rounding to the nearest 250 mg)

So, the maximum dose would be approximately 2250 mg per dose, three times a day.

It's important to note that these doses should be individualized based on the patient's response and therapeutic goals, and treatment may need to be temporarily interrupted if serum ferritin consistently falls below 500 mcg/L.

Deferiprone (Ferriprox) Dose in Children:

The safety and efficacy of the drug in children have not been established.

Pregnancy Risk Factor D

• Studies on animals have shown negative effects on reproduction with the use of deferiprone.
• While there's not much data on humans, it's possible that deferiprone might harm a developing fetus if taken during pregnancy.
• Therefore, women who could become pregnant should avoid getting pregnant while taking deferiprone.

Deferiprone use during breastfeeding:

• It's unclear whether deferiprone passes into breast milk.
• Because there's a chance it could cause serious problems for the nursing baby, the manufacturer suggests deciding whether to stop breastfeeding or stop taking the medication, considering how important the treatment is for the mother.

Ferriprox Dose in Kidney Disease:

The manufacturer's labeling for deferiprone does not include any specific dosage adjustments for individuals with renal impairment.

Ferriprox Dose in Liver disease:

• The manufacturer's labeling for deferiprone does not include any specific dosage adjustments for individuals with hepatic impairment.
• However, it's important to note that deferiprone has not been studied in patients with severe hepatic impairment.
• Therefore, caution should be exercised when administering deferiprone to patients with hepatic impairment, and close monitoring for potential adverse effects is recommended.

Common Side Effects of Deferiprone (Ferriprox):

• Gastrointestinal:
  • Nausea
• Genitourinary:
  • Urine discoloration

Less Common Side Effects of Deferiprone (Ferriprox):

• Central nervous system:
  • Headache
• Gastrointestinal:
  • Vomiting
  • Abdominal distress
  • Abdominal pain
  • Increased appetite
  • Diarrhea
  • Dyspepsia
  • Weight gain
  • Decreased appetite
• Hematologic & oncologic:
  • Neutropenia
  • Agranulocytosis
• Hepatic:
  • Increased serum ALT
  • Increased serum AST
• Neuromuscular and skeletal:
  • Arthralgia
  • Back pain
  • Limb pain
  • Arthropathy

Contraindications to Deferiprone (Ferriprox):

• In addition to hypersensitivity to deferiprone or any component of the formulation, Canadian labeling for deferiprone lists additional contraindications not found in US labeling.
• These include severe neutropenia (absolute neutrophil count <500/mm³), pregnancy, and breastfeeding.
• It's important for healthcare providers to be aware of these contraindications when considering deferiprone therapy for patients in Canada.

Warnings and Precautions

Agranulocytosis and Neutropenia: [US Boxed Warning]:

• Deferiprone carries a US Boxed Warning due to the risk of agranulocytosis, a condition characterized by a severe decrease in white blood cells, which can lead to serious infections, some of which may be fatal.
• Agranulocytosis may be preceded by neutropenia, so it's crucial to monitor the absolute neutrophil count (ANC) before starting treatment and weekly thereafter.
• If an infection develops, treatment should be interrupted, and ANC should be monitored more frequently.
• Patients should report any symptoms indicating infection promptly.
• If neutropenia (ANC <1,500/mm³) occurs, treatment should be interrupted, and other medications potentially associated with neutropenia should be withheld.
• Daily monitoring of complete blood count (CBC), white blood cell count corrected for nucleated red blood cells (corrected WBC), ANC, and platelets should be conducted until ANC recovery.
• Hospitalization may be necessary if ANC drops below 500/mm³, along with other clinically appropriate management.
• Treatment with deferiprone should not be resumed unless the potential benefits outweigh the risks.
• Neutropenia and agranulocytosis are generally reversible upon discontinuation of deferiprone.
• The mechanism for deferiprone-induced agranulocytosis is unknown, so concurrent use with other agents associated with neutropenia (or agranulocytosis) should be avoided.

Hepatotoxicity:

• Hepatotoxicity, characterized by elevated ALT (alanine aminotransferase) values, has been reported with the use of deferiprone.

Hypersensitivity:

• Hypersensitivity reactions, such as Henoch-Schönlein purpura (immunoglobulin A vasculitis), urticaria, and periorbital edema with skin rash, have been reported with the use of deferiprone.

Zinc deficiency:

• Deferiprone use has been associated with lower plasma zinc concentrations, which may lead to zinc deficiency.
• Healthcare providers should monitor zinc levels in patients receiving deferiprone and consider supplementation if necessary to maintain adequate zinc levels.
• This proactive approach helps prevent potential complications associated with zinc deficiency during deferiprone therapy.

Deferiprone: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
UGT1A6 Inhibitors	May increase the serum concentration of Deferiprone.
Risk Factor D (Consider therapy modification)
Polyvalent Cation Containing Products	May decrease the serum concentration of Deferiprone. Management: Separate administration of deferiprone and oral medications or supplements that contain polyvalent cations by at least 4 hours.
Risk Factor X (Avoid combination)
Myelosuppressive Agents	May enhance the neutropenic effect of Deferiprone.

Monitoring parameters:

• Serum Ferritin: Check every 2-3 months to monitor iron levels in the blood.
• Absolute Neutrophil Count (ANC):
  • Baseline: Check before starting treatment.
  • During Treatment: Monitor weekly.
  • If ANC drops below 1,500/mm³:
    • Monitor Complete Blood Count (CBC), White Blood Cell count (corrected for nucleated Red Blood Cells), ANC, and platelets daily until ANC recovers.
• Alanine Aminotransferase (ALT): Monitor monthly to detect liver function changes.
• Zinc Levels: Check periodically to monitor for potential zinc deficiency.
• Signs or Symptoms of Infection: Patients should report any signs or symptoms of infection promptly for appropriate evaluation and management.

How to administer Deferiprone (Ferriprox)?

• Timing: Take deferiprone in the morning, at midday, and in the evening for optimal effectiveness.
• With Food: Taking deferiprone with food may help decrease nausea.
• Avoid Polyvalent Cations: Administer deferiprone at least 4 hours apart from medications or supplements containing polyvalent cations such as iron, aluminum, or zinc to prevent interactions that may affect absorption.

Mechanism of action of Deferiprone (Ferriprox):

• Deferiprone is an iron-chelating agent that specifically targets ferric ions (iron III) in the body.
• It forms a complex with ferric ions in a ratio of 3:1 (deferiprone to iron), effectively binding to excess iron and facilitating its elimination through urine.
• While deferiprone primarily targets iron, it has a lower affinity for other metals such as copper, aluminum, and zinc, which means it is less likely to bind to these metals and interfere with their normal physiological functions.

Absorption:

• Rapid absorption into the bloodstream.

Distribution:

• In thalassemia patients, the distribution volume is approximately 1.6 liters per kilogram of body weight.

Protein Binding:

• Less than 10% of deferiprone is bound to proteins in the bloodstream.

Metabolism:

• The primary metabolic pathway is through UGT 1A6 enzymes. The major metabolite, 3-O-glucuronide, does not have iron-binding capacity.

Bioavailability:

• Both tablets and oral solutions have comparable bioavailability.

Half-Life Elimination:

• The half-life of deferiprone elimination is approximately 2 hours.

Time to Peak:

• Peak plasma concentrations are typically reached around 1 to 2 hours after administration.

Excretion:

• Deferiprone and its metabolites are primarily excreted in urine, accounting for 75% to 90% of the administered dose, with the majority being excreted as the metabolite.

International Brands of Deferiprone:

• Ferriprox
• Feripon
• Kelfer
• Neferi

Deferiprone Brand Names in Pakistan:

Deferiprone Tablets 500 mg
Ferinil	Global Pharmaceuticals
Ferriprox	Ici Pakistan Ltd.

Deferiprone Capsules 500 mg
Kelfer	A. J. Mirza Pharma (Pvt) Ltd