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

Note:

Round the dose to the nearest 250 mg (or 1/2 tablet) or 2.5 mL (oral solution). The treatment may need interruption if the serum ferritin is persistently below 500 mcg/L.

Deferiprone (Ferriprox) Dose in the treatment of Transfusional iron overload:

• 25 mg/kg orally 3 times/day (75 mg/kg/day) initially,
• The dose should be individualized based on the response to treatment and the target ferritin levels.
• The maximum recommended dose is 33 mg/kg thrice daily (99 mg/kg/day).

Deferiprone (Ferriprox) Dose in Children:

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

Pregnancy Risk Factor D

• Adverse events have been observed in animal studies.
• Because of the potentially serious adverse events in the fetus, the manufacturer recommends avoiding the drug during pregnancy.

Deferiprone use during breastfeeding:

• The excretion of the drug into breastmilk is not known.
• The manufacturer recommends discontinuing the drug or breastfeeding considering the benefits and risks.

Ferriprox Dose in Kidney Disease:

The manufacturer has not provided any adjustments in the dose in patients with renal disease.

Ferriprox Dose in Liver disease:

• The manufacturer has not recommended any adjustments in the dose.
• It has not been studied in patients with severe liver disease.

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):

• Allergic reactions to the drug or any component of the formulation
• Severe neutropenia (ANC <500/mm³)
• Pregnancy
• Breastfeeding

Warnings and Precautions

• Agranulocytosis and Neutropenia: [US Boxed Warning]:

  • Agranulocytosis may occur that may result in serious infection resulting in fatalities.
  • Preceding neutropenia may occur. ANC (Absolute neutrophil counts should be monitored before treatment initiation and at weekly intervals.
  • Patients who develop an infection may need to interrupt the treatment and monitor ANC daily.
  • Patients should be asked to report any symptoms suggestive of an infection such as fever or sore throat.
  • If the ANC falls to less than 1500/mm³, treatment must be withheld including medications that can cause neutropenia.
  • CBC and corrected WBC, ANC, and platelets daily should be monitored until ANC recovery.
  • Patients may need hospitalization if the ANC falls to less than 500/mm³. Treatment must not be resumed unless the benefits outweigh the risks.
  • Treatment interruption may result in an improvement in the hematological parameters.

• Hepatotoxicity:

  • Hepatotoxicity may occur and manifest as rising ALT levels.
  • Consider withholding the treatment if persistent ALT elevation is noted.

• Hypersensitivity:

  • Allergic reactions may occur that may manifest as Ig A vasculitis (Henoch-Schönlein purpura), skin rash, urticaria, and periorbital edema.

• Zinc deficiency:

  • Zinc levels may reduce with treatment and should be monitored periodically.
  • If zinc levels are reduced, supplementation may be necessary.

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

Monitoring parameters:

• Monitor serum ferritin every 2-3 months
• ANC at baseline and weekly during treatment.
  • if ANC <1,500/mm³, monitor CBC, WBC (corrected for nucleated RBCs), ANC, and platelets daily until ANC recovery;
• ALT monthly
• zinc levels;
• signs or symptoms of infection

How to administer Deferiprone (Ferriprox)?

• Administer the drug with meals to avoid gastrointestinal side effects.
• Concomitant administration with medicines containing polyvalent cations should be avoided.
• A 4-hour interval should be kept between the drug and administration of cations (iron, zinc, or aluminum).

Mechanism of action of Deferiprone (Ferriprox):

• It is an oral iron-chelating agent that has a high affinity for the ferric form of iron.
• It binds to the iron in a 3:1 (deferiprone: iron) complex that is then excreted in the urine.
• Its affinity for other metals such as copper, zinc, and aluminum is very low.

Absorption:

• Rapid

Protein binding:

• <10%

Metabolism:

• Primarily by UGT 1A6;
• major metabolite (3-O-glucuronide) lacks the capacity to bind iron.

Bioavailability:

• The oral solution and the tablets are considered to be bioequivalent

Half-life elimination:

• About 2 hours

Time to peak:

• About 1-2 hours

Excretion:

• Urine 75% to 90% (primarily as metabolite).

International Brands of Deferiprone:

• Ferriprox
• Feripon
• Kelfer
• Neferi

Deferiprone Brand Names in Pakistan: