Ferriprox (deferiprone) for sickle cell disease

Last updated May 16, 2024, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD

What is Ferriprox for sickle cell disease?

Ferriprox (deferiprone) is an oral medication that’s used to treat iron overload — a condition marked by dangerously high iron levels in the body — that occurs as a complication of blood transfusions in children and adults with sickle cell disease (SCD).

The therapy, originally developed by ApoPharma and currently marketed by Chiesi Global Rare Diseases, also is approved to treat transfusion-induced iron overload in other types of anemia and in thalassemia syndromes, a group of related genetic blood disorders.

Ferriprox is supplied in the form of oral tablets and as an oral solution.

Therapy snapshot

How does Ferriprox work?

Treating blood disorders like SCD often involves blood transfusions, where blood or blood cells from a donor are infused into the patient’s bloodstream. Transfusions can be lifesaving, but like any medical procedure, they also can cause complications.

Since blood naturally has a lot of iron, transfusions can lead to iron overload, especially when given repeatedly within a short period of time. When iron levels are too high, iron can form damaging deposits in internal organs, particularly the liver, heart, and pancreas.

Deferiprone, the active agent in Ferriprox, is an iron chelator, or a molecule that can bind and neutralize iron, helping to eliminate it from the body, mainly through urine. In essence, the therapy sponges up excess iron from the body, working to reduce its levels and prevent the damaging consequences of iron overload.

Who with sickle cell disease can take Ferriprox?

The U.S. Food and Drug Administration (FDA) approved Ferriprox as a treatment for transfusion-induced iron overload in adults and children with SCD in April 2021. The oral solution formulation of the medication is authorized for use in sickle cell patients ages 3 and older, while the oral tablet version is authorized for patients ages 8 and older. Ferriprox also is approved to treat transfusion-induced iron overload in sickle cell patients in other countries, including Brazil and Canada.

In the U.S., Ferriprox initially was approved by the FDA in October 2011 as a treatment for transfusion-induced iron overload in people with thalassemia who didn’t respond adequately to prior treatment with an iron chelator.

Who should not take Ferriprox?

Ferriprox is contraindicated, or not recommended, for people with a known allergy to any of its ingredients.

The prescribing information of the therapy’s tablet and oral solution formulation also comes with a boxed warning that the therapy can severely reduce the number of neutrophils, a type of white blood cell, which increases a person’s risk of serious infections and death. Patients showing signs of infection or with low neutrophil counts should interrupt treatment with Ferriprox.

The safety and effectiveness of Ferriprox in treating transfusion-induced iron overload in patients with myelodysplastic syndrome, a type of blood cancer, or Diamond Blackfan anemia, a rare type of anemia, have not been established.

How is Ferriprox administered in sickle cell disease?

Ferriprox is supplied in the form of an oral solution and oral tablets. Patients with difficulties swallowing tablets may consider using the oral solution formulation.

The oral solution contains 100 mg/mL of the medication in a solution that’s clear and reddish orange in color. For the oral solution, the recommended starting dose is 25 milligrams of medication per kilogram of body weight (mg/kg), taken three times per day, for a total daily dose of 75 mg/kg. Based on how the patient responds to treatment, the dose then can be adjusted up to a maximum of 33 mg/kg three times per day, for a total daily dose of 99 mg/kg.

To reduce the chances of gastrointestinal issues when starting treatment, patients may start taking Ferriprox at a lower daily dose of 45 mg/kg and gradually increase the daily dosage (in 15 mg/kg weekly increments) until reaching their full prescribed dose.

When taking Ferriprox oral solution, patients should use the measuring cup supplied with the medication to measure the amount of solution they need to ingest. After swallowing the prescribed dose, they should add 10 to 15 mL of water to the measuring cup to mix it with any remnants of the medication. That mixture then also should be swallowed. Ferriprox oral solution should be stored at room temperature, protected from light. Once opened, the bottle containing the medication should be used within 35 days. After that period, the bottle should be discarded, along with any remaining medication.

Recommended dosing for the oral tablet formulation of Ferriprox is the same as that for the oral solution: the recommended starting daily dose is 75 mg/kg, which can be increased to 99 mg/kg as needed. A lower starting daily dose of 45 mg/kg followed by weekly increments also may be used to minimize the chances of gastrointestinal upset.

Three versions of Ferriprox oral tablets are available, with different dosing strengths and allowing for slightly different dosing schedules, with tablets being taken with food either two or three times each day:

• Capsule-shaped, film-coated, white to off-white 1,000 mg tablets with functional scoring, engraved with “APO” and “1000” on one side and plain on the other, which should be taken three times per day.
• Capsule-shaped, white to off-white 1,000 mg tablets with functional scoring, engraved with “FPX” and “DR” on one side and “APO” and “1000” on the other, which should be taken twice each day, approximately 12 hours apart, with food.
• Capsule-shaped, film-coated, white to off-white 500 mg tablets with functional scoring, imprinted with “APO” and “500” on one side and plain on the other, which should be taken three times per day.

All three versions of Ferriprox oral tablets should be stored at room temperature.

During treatment, it is recommended that ferritin levels be checked regularly (every two to three months) to assess the effects of Ferriprox on body iron stores. If ferritin levels in the blood are consistently below 500 micrograms per liter, patients and physicians should consider temporarily interrupting treatment until they are above that threshold. Of note, ferritin is a protein that’s responsible for storing iron inside cells; low levels of ferritin usually indicate a depletion in body iron stores.

Because Ferriprox may interact with positively charged ions, such as aluminum and zinc, the medication should be administered with a minimum four-hour interval of other medicines or supplements containing positively charged ions, including antacids.

Ferriprox in sickle cell disease clinical trials

The approval of Ferriprox in the U.S. for transfusion-induced iron overload associated with SCD or other anemias was supported by data from a Phase 3b/4 clinical trial called FIRST (NCT02041299), which enrolled more than 200 patients, most of whom had SCD.

Trial participants were treated for about one year with either oral Ferriprox or with deferoxamine, an iron chelator medication marketed under the brand name Desferal by Novartis and given as an under-the-skin injection. The study’s main goal was to test if Ferriprox was as effective as deferoxamine at reducing liver iron concentration.

Results showed that both treatments had a comparable effect, with liver iron concentration decreasing by slightly more than 4 milligrams per gram of dry weight (mg/g dw) with both therapies after one year.

A subgroup analysis focusing only on children and adolescents also found comparable effects, with both medications reducing iron concentration in the liver by more than 3 mg/g dw after one year.

After the initial study, 134 patients who completed FIRST elected to continue in an open-label extension study, FIRST-EXT (NCT02443545), in which all were treated with Ferriprox for an additional two years. Available data showed that iron levels in the liver continued to fall over time for up to three years.

Common side effects of Ferriprox

The most common side effects of Ferriprox in people with SCD or other anemias include:

• fever
• pain in the abdomen, back, joints, throat, bones, and/or extremities
• headache
• cough
• vomiting and/or nausea
• increased levels of liver enzymes
• sickle cell crisis
• low neutrophil counts.

Low immune cell counts

Ferriprox’s prescribing information carries a boxed warning noting it can severely reduce the levels of neutrophils, a type of immune cell critical for fighting off infections. Low neutrophil counts (less than 1.5 billion cells per liter) are referred to as neutropenia, and extremely low counts (less than 0.5 billion cells per liter) as agranulocytosis. The use of Ferriprox may result in fatal agranulocytosis, or lead to the development of neutropenia, which may precede the onset of agranulocytosis.

Low neutrophil counts can increase the risk of serious and life-threatening infections. Patients should immediately report any symptoms suggesting the presence of an infection while on Ferriprox.

Neutrophil counts also should be checked before patients start treatment with Ferriprox and regularly during  treatment. It is recommended that absolute neutrophil counts be checked weekly in the first six months of treatment, once every two weeks in the following six months, and every two to four weeks after the first year.

If patients develop neutropenia or have any symptoms indicative of an infection, treatment with Ferriprox should be interrupted. If agranulocytosis occurs, hospitalization and other intensive management strategies to prevent serious infection may be warranted.

People who previously developed neutropenia or agranulocytosis should only resume treatment with Ferriprox if the benefits clearly outweigh the potential risks.

Ferriprox should not be given to patients taking other medications that could cause neutropenia or agranulocytosis. In cases where co-administration is unavoidable, it is recommended that absolute neutrophil counts be closely monitored.

Increases in liver enzymes

Ferriprox may cause elevations in liver enzymes, which can be a sign of liver damage. Liver enzyme levels should be checked at least once every month for patients taking Ferriprox. If levels are persistently elevated, treatment interruption should be considered. Liver enzyme levels also should be checked before patients start treatment with Ferriprox.

Zinc deficiency

People treated with Ferriprox may have abnormally low levels of zinc. Zinc levels should be checked at least once a year for patients on Ferriprox, and supplements should be given if patients have a deficiency. Zinc levels also should be checked prior to treatment initiation.

Fetal toxicity and other considerations for pregnancy and breastfeeding

Ferriprox has not been rigorously studied in women who are pregnant or breastfeeding, but data from animal studies suggest the therapy can cause genotoxicity and be harmful to the developing fetus if used during pregnancy. Genotoxicity is the ability of a compound or therapy to cause damage to a cell’s genetic material. If this type of damage occurs in germ cells (sperm or egg cells) used during conception, the resulting fetus may be harmed.

Specifically, animal studies in rats and rabbits have shown the use of Ferriprox during pregnancy led to various types of malformations in the fetus, as well as to fetal or embryo loss.

Animal studies also indicated the medication can potentially cause complications in nursing infants if used during breastfeeding, including promoting the development of tumors.

For these reasons, Ferriprox is not recommended for use in women who are pregnant or breastfeeding.

Due to the risks of genotoxicity and the potential harmful effects of Ferriprox to a developing fetus, it is recommended that female patients with the capacity to become pregnant utilize an effective form of contraception while on the medication and for at least six months after stopping treatment. Additionally, it is recommended that a pregnancy test be made prior to treatment initiation in female patients of reproductive potential. Male patients of similar potential also should use effective forms of contraception while on Ferriprox and for at least three months after the last dose.

Likewise, due to the potential complications Ferriprox can cause to nursing infants, it is recommended that women taking the medication refrain from breastfeeding during treatment and for at least two weeks after their last dose.

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