Ferriprox

Deferiprone binds to iron and removes it from the blood stream.

Deferiprone is used to treat iron overload caused by blood transfusions in people with certain hereditary red blood cell disorders (thalassemia syndrome).

Deferiprone may also be used for purposes not listed in this medication guide.

Do not use deferiprone if you are pregnant. It could harm the unborn baby.

Stop using this medicine and call your doctor right away if you have signs of infection such as: fever, chills, body aches, flu symptoms, or sores in your mouth and throat.

You should not use deferiprone if you are allergic to it.

To make sure deferiprone is safe for you, tell your doctor if you have:

• liver disease; or
• a weak immune system.

This medicine can harm an unborn baby or cause birth defects. Do not use if you are pregnant, and tell your doctor right away if you become pregnant. Use effective birth control to prevent pregnancy while you are using this medicine.

It is not known whether deferiprone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking deferiprone.

Deferiprone is not approved for use by anyone younger than 18 years old.

Deferiprone binds to iron and removes it from the blood stream.

Deferiprone is used to treat iron overload caused by blood transfusions.

Deferiprone may also be used for purposes not listed in this medication guide.

Heavy metal antagonist; chelates iron.1 4 5 10 13 14 18

Contraindications

• Known hypersensitivity to deferiprone or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Risk of agranulocytosis, which may be preceded by neutropenia; may result in potentially life-threatening infections.1 17 Agranulocytosis reported in 1.7% of patients in clinical trials; agranulocytosis and neutropenia usually resolve upon drug discontinuance.1

Measure ANC before initiating deferiprone and every week during therapy.1 17 If neutropenia (ANC <1500/mm3) develops, temporarily discontinue deferiprone and any other drugs that may cause neutropenia.1 Obtain CBC, including WBC count corrected for the presence of nucleated RBCs, ANC, and platelet count, daily until neutropenia resolves (ANC ≥1500/mm3).1 If agranulocytosis (ANC <500/mm3) develops, discontinue deferiprone and initiate appropriate clinical treatment, including hospitalization if necessary.1

In patients who have experienced neutropenia or agranulocytosis, do not resume deferiprone therapy unless potential benefit outweighs potential risk.1

If infection occurs, interrupt deferiprone therapy and monitor ANC more frequently.1

Other Warnings/Precautions

May cause fetal harm; embryofetal lethality and teratogenicity demonstrated in animals.1 If used during pregnancy or if the patient becomes pregnant, apprise of potential fetal hazard.1

Hypersensitivity reactions (e.g., Henoch-Schönlein purpura, urticaria, periorbital edema with skin rash) reported.1

Effect on QT interval not studied thoroughly to date.1 Torsades de pointes reported in a patient with a history of QT-interval prolongation who was receiving deferiprone.1

Use with caution in patients who may be at increased risk for QT-interval prolongation (e.g., patients with CHF, bradycardia, cardiac hypertrophy, hypokalemia, or hypomagnesemia and those receiving diuretics).1

Increased serum transaminase concentrations, sometimes resulting in drug discontinuance, reported.1 Monitor serum ALT concentrations monthly; consider interrupting therapy if transaminase concentrations are persistently increased.1

Early reports that deferiprone may worsen liver fibrosis13 23 not confirmed in subsequent clinical trials.5 13 24

Decreased plasma zinc concentrations reported.1 Monitor serum zinc concentrations and administer zinc supplements if necessary.1

Specific Populations

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Not known whether deferiprone is distributed into milk.1 Discontinue nursing or the drug.1

Safety and efficacy not established.1

Safety and efficacy not established.1 (See Geriatric Patients under Dosage and Administration.)

Not studied conclusively.1

Not studied specifically.1

Common Adverse Effects

Chromaturia, nausea, vomiting, abdominal pain/discomfort, arthralgia, increased ALT, decreased neutrophil count, neutropenia.1

Storage

Oral

20–25°C (may be exposed to 15–30°C).1

In the U.S.

• Ferriprox

Available Dosage Forms:

• Tablet
• Solution

Therapeutic Class: Heavy Metal Chelator

Ferriprox® (deferiprone) is indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate.

Approval is based on a reduction in serum ferritin levels. There are no controlled trials demonstrating a direct treatment benefit, such as improvement in disease-related symptoms, functioning, or increased survival [see Clinical Studies (14)].

Limitation of Use:

• Safety and effectiveness have not been established for the treatment of transfusional iron overload in patients with other chronic anemias.

Agranulocytosis/Neutropenia

Fatal agranulocytosis can occur with Ferriprox use. Ferriprox can also cause neutropenia, which may foreshadow agranulocytosis. Measure the absolute neutrophil count (ANC) before starting Ferriprox therapy and monitor the ANC weekly on therapy.

Interrupt Ferriprox therapy if neutropenia develops (ANC < 1.5 x 109/L).

Interrupt Ferriprox if infection develops, and monitor the ANC more frequently.

Advise patients taking Ferriprox to immediately interrupt therapy and report to their physician if they experience any symptoms indicative of infection.

In pooled clinical trials, the incidence of agranulocytosis was 1.7% of patients. The mechanism of Ferriprox-associated agranulocytosis is unknown. Agranulocytosis and neutropenia usually resolve upon discontinuation of Ferriprox, but there have been reports of agranulocytosis leading to death.

Implement a plan to monitor for and to manage agranulocytosis/neutropenia prior to initiating Ferriprox treatment.

For neutropenia (ANC < 1.5 x 109/L and > 0.5 x 109/L):

Instruct the patient to immediately discontinue Ferriprox and all other medications with a potential to cause neutropenia.

Obtain a complete blood cell (CBC) count, including a white blood cell (WBC) count corrected for the presence of nucleated red blood cells, an absolute neutrophil count (ANC), and a platelet count daily until recovery (ANC ≥ 1.5 x 109/L).

For agranulocytosis (ANC < 0.5 x 109/L):

Consider hospitalization and other management as clinically appropriate.

Do not resume Ferriprox in patients who have developed agranulocytosis unless potential benefits outweigh potential risks. Do not rechallenge patients who develop neutropenia with Ferriprox unless potential benefits outweigh potential risks.

Embryofetal Toxicity

Based on evidence of genotoxicity and developmental toxicity in animal studies, Ferriprox can cause fetal harm when administered to a pregnant woman. In animal studies, administration of deferiprone during the period of organogenesis resulted in embryofetal death and malformations at doses lower than equivalent human clinical doses. If Ferriprox is used during pregnancy or if the patient becomes pregnant while taking Ferriprox, the patient should be apprised of the potential hazard to the fetus. Women of reproductive potential should be advised to avoid pregnancy when taking Ferriprox [see Use in Specific Populations (8.1) and Nonclinical Toxicology (13.1)].

Laboratory Tests

Serum Liver Enzyme Activities

In clinical studies, 7.5% of 642 subjects treated with Ferriprox developed increased ALT values. Four (0.62%) Ferriprox-treated subjects discontinued the drug due to increased serum ALT levels and 1 (0.16%) due to an increase in both ALT and AST.

Monitor serum ALT values monthly during therapy with Ferriprox, and consider interruption of therapy if there is a persistent increase in the serum transaminase levels.

Plasma Zinc Concentration

Decreased plasma zinc concentrations have been observed on Ferriprox therapy. Monitor plasma zinc, and supplement in the event of a deficiency.

Ferriprox® (Feh’ ri prox)

(deferiprone)

tablets 

Read this Medication Guide before you start taking Ferriprox and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about Ferriprox?

Ferriprox can cause serious side effects, including a very low white blood cell count in your blood.  One type of white blood cell that is important for fighting infections is called a neutrophil. If your neutrophil count is low (neutropenia), you may be at risk of developing a serious infection that can lead to death. Neutropenia is common with Ferriprox and can become severe in some people. Severe neutropenia is known as agranulocytosis. If you develop agranulocytosis, you will be at risk of developing serious infections that can lead to death.

Your healthcare provider should do a blood test before you start Ferriprox and weekly during treatment to check your neutrophil count. If you develop neutropenia, your healthcare provider should check your blood counts every day until your white blood cell count improves. 

Stop taking Ferriprox and get medical help right away if you develop any of these symptoms of infection:

• fever
• sore throat or mouth sores
• flu-like symptoms
• chills and severe shaking

See “What are the possible side effects of Ferriprox?” for more information about side effects.

What is Ferriprox?

Ferriprox is a prescription medicine used to treat people with thalassemia syndromes who have iron overload from blood transfusions, when current iron removal (chelation) therapy does not work well enough.

It is not known if Ferriprox tablets are safe and effective:

• to treat iron overload due to blood transfusions in people with any other type of anemia that is long lasting (chronic)
• in children
• in people with severe liver problems

Who should not take Ferriprox?

Do not take Ferriprox if you are allergic to deferiprone or any of the ingredients in Ferriprox. See the end of this Medication Guide for a complete list of ingredients in Ferriprox.

What should I tell my healthcare provider before taking Ferriprox?

Before you take Ferriprox, tell your healthcare provider if you:

• have liver problems
• have any other medical conditions.
• are pregnant or plan to become pregnant. Ferriprox can harm your unborn baby. You should avoid becoming pregnant while taking Ferriprox. Tell your healthcare provider right away if you become pregnant or plan to become pregnant while taking Ferriprox.
• are breastfeeding or plan to breastfeed. It is not known if Ferriprox passes into your breast milk. You and your healthcare provider should decide if you will take Ferriprox or breastfeed.  You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Especially tell your healthcare provider if you take:

• other medicines that can cause a lowering of your neutrophil count
• antacids or mineral supplements that contain: iron, aluminum, and zinc.  Allow at least 4 hours between taking Ferriprox and any of these products.

Ask your healthcare provider or pharmacist if your medicine is one that is listed above.

Know the medicines you take.  Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Ferriprox?

• Take Ferriprox exactly as prescribed by your healthcare provider. Do not change your dose of Ferriprox unless your healthcare provider tells you to.
• Your healthcare provider will tell you how many Ferriprox tablets to take.
• Ferriprox is taken 3 times each day.  Take your first dose in the morning, the second dose at mid-day, and third dose in the evening.
• You can take Ferriprox with or without food.
• Taking Ferriprox with meals may help reduce nausea.
• If you take too much Ferriprox, call your healthcare provider.
• If you do miss a dose take it as soon as you remember.  If it is almost time for your next dose, skip the missed dose and then continue with your regular schedule.  Do not try to catch-up or take 2 doses at the same time to make up for a missed dose.

What are the possible side effects of Ferriprox?

Ferriprox can cause serious side effects, including:

• See “What is the most important information I should know about Ferriprox?”
• Increased liver enzyme levels in your blood. Your healthcare provider should do monthly blood test to check your liver function during treatment with Ferriprox.

The most common side effects of Ferriprox include:

• reddish-brown colored urine.  This is not harmful and is expected when you are taking Ferriprox.
• nausea
• vomiting
• stomach-area (abdominal) pain
• joint pain
• low neutrophil count. See “What is the most important information I should know about Ferriprox?”

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Ferriprox. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800-FDA-1088.

How should I store Ferriprox?

• Store Ferriprox at room temperature between 68○F to 77○F (20○C to 25○C).

Keep Ferriprox and all medicines out of the reach of children.

General information about the safe and effective use of Ferriprox.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Ferriprox for a condition for which it was not prescribed. Do not give Ferriprox to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Ferriprox. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about Ferriprox that is written for health professionals.

For more information call 1-866-949-0995.

What are the ingredients in Ferriprox?

Active ingredients: deferiprone

Inactive ingredients:

   Tablet core: microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide.

   Coating: hydroxypropyl methyl cellulose, polyethylene glycol, titanium dioxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by:

ApoPharma USA, Inc., Rockville, MD, United States of America, 20850.

Manufactured by:

Apotex Inc., Toronto, Ontario, Canada, M9L 1T9.

Revised February 2015

Trademark disclaimers.

Do not use Ferriprox if you are pregnant. It could harm the unborn baby.

Stop using this medicine and call your doctor right away if you have signs of infection such as: fever, chills, body aches, flu symptoms, or sores in your mouth and throat.