Deferiprone (Monograph)

Brand name: Ferriprox
Drug class: Heavy Metal Antagonists

Medically reviewed by Drugs.com on Aug 29, 2023. Written by ASHP.

[Web]

Introduction

Chelating agent with affinity for ferric ions.

Uses for Deferiprone

Transfusional Iron Overload

Oral tablets are used for treatment of transfusional iron overload in adult and pediatric patients ≥8 years of age with thalassemia syndromes, sickle cell disease, or other anemias.

Oral solution is used for treatment of transfusional iron overload in adult and pediatric patients ≥3 years of age with thalassemia syndromes, sickle cell disease, or other anemias.

Safety and efficacy for treatment of transfusional iron overload in patients with myelodysplastic syndrome or Diamond Blackfan anemia not established.

Designated an orphan drug by FDA for treatment of iron overload in patients with hematologic disorders requiring chronic transfusion therapy.

Guidelines generally recommend chelation therapy, including deferiprone, for transfusion-dependent iron overload; the optimal regimen should be tailored for the individual patient and their clinical situation.

Deferiprone Dosage and Administration

General

Pretreatment Screening

• Measure ANC before treatment with deferiprone.

• Measure serum ALT values before treatment.

• Measure zinc levels before treatment.

• Perform pregnancy testing in females of reproductive potential prior to treatment.

Patient Monitoring

• Monitor ANC weekly for the first 6 months of therapy, once every 2 weeks for the next 6 months of therapy, and every 2–4 weeks (or at the patient’s blood transfusion interval if there have been no interruptions due to any decrease in ANC) after 1 year of therapy.

• Monitor serum ALT values monthly during treatment with deferiprone.

• Monitor plasma zinc levels at least annually during treatment.

• Monitor serum ferritin concentration every 2–3 months during treatment to assess the effects of deferiprone on body iron stores. If serum ferritin concentration is decreased consistently to <500 mcg/L, consider temporary interruption of therapy until serum ferritin rises to >500 mcg/L.

Dispensing and Administration Precautions

• Deferiprone tablets are available in 3 formulations: 2 different 1000 mg formulations (a twice-a-day 1000-mg formulation and a three-times-a-day 1000-mg formulation) and a 500-mg formulation). These formulations have different dosing regimens to achieve the same total daily dosage. Prior to prescribing and dispensing, ensure that the formulation is appropriate for the dosing regimen in order to prevent medication errors. Each formulation has distinct identifying characteristics; consult the prescribing information for further details.

Administration

Oral Administration

Administer orally (as tablets or solution).

Administer tablets orally 2 or 3 times daily depending on the formulation used. For the twice-a-day 1000-mg tablet formulation, administer the first dose in the morning and second dose in the evening, approximately 12 hours apart. For the three-times-a-day 1000-mg tablet formulation and the 500-mg tablet, administer the first dose in the morning, second dose at mid-day, and third dose in the evening.

Administer oral solution 3 times daily with the first dose in the morning, second dose at mid-day, and third dose in the evening.

Administration with meals may help reduce nausea.

Dosage

Dosing of deferiprone based on actual body weight.

Pediatric Patients

Transfusional Iron Overload

Oral

Dosage for 1000-mg twice-daily tablets in pediatric patients ≥8 years of age: Initial dosage of 75 mg/kg per day (based on actual body weight) administered in 2 divided doses (approximately 12 hours apart) with food. Round calculated dose to nearest 500 mg (one-half of 1000-mg tablet).

Adjust dosage up to a maximum of 99 mg/kg per day, administered in 2 divided doses, based on individual patient response and therapeutic goals.

To minimize GI upset when initiating treatment, may start dosage at 45 mg/kg per day and increase weekly by increments of 15 mg/kg per day until full prescribed dose is achieved.

Dosage for 1000-mg three times a day tablets in pediatric patients ≥8 years of age: Initial dosage of 75 mg/kg per day (based on actual body weight) administered in 3 divided doses. Round calculated dose to nearest 500 mg (one-half of 1000-mg tablet).

Adjust dosage up to a maximum of 99 mg/kg per day, administered in 3 divided doses, based on individual patient response and therapeutic goals.

To minimize GI upset when initiating treatment, may start dosage at 45 mg/kg per day and increase weekly by increments of 15 mg/kg per day until full prescribed dose is achieved.

Dosage for 500-mg tablets in pediatric patients ≥8 years of age: Initial dosage of 75 mg/kg per day (based on actual body weight) administered in 3 divided doses. Round calculated dose to nearest 250 mg (one-half of 500-mg tablet).

Adjust dosage up to maximum of 99 mg/kg per day, administered in 3 divided doses, based on individual patient response and therapeutic goals.

To minimize GI upset when initiating treatment, may start dosage at 45 mg/kg per day and increase weekly by increments of 15 mg/kg per day until full prescribed dose is achieved.

Dosage for oral solution in pediatric patients ≥3 years of age: Initial dosage of 25 mg/kg (based on actual body weight) 3 times daily (75 mg/kg per day). Round calculated dose to the nearest 2.5 mL.

Adjust dosage up to a maximum of 33 mg/kg 3 times daily (99 mg/kg per day) based on individual patient response and therapeutic goals.

To minimize GI upset when initiating treatment, may start dosage at 45 mg/kg per day and increase weekly by increments of 15 mg/kg per day until full prescribed dose is achieved.

Adults

Transfusional Iron Overload

Oral

Dosage for 1000-mg twice-daily tablets: Initial dosage of 75 mg/kg per day (based on actual body weight) administered in 2 divided doses (approximately 12 hours apart) with food. Round calculated dose to nearest 500 mg (one-half of 1000-mg tablet).

Adjust dosage up to a maximum of 99 mg/kg per day, administered in 2 divided doses, based on individual patient response and therapeutic goals.

To minimize GI upset when initiating treatment, may start dosage at 45 mg/kg per day and increase weekly by increments of 15 mg/kg per day until full prescribed dose is achieved.

Dosage for 1000-mg three times a day tablets: Initial dosage of 75 mg/kg per day (based on actual body weight) administered in 3 divided doses. Round calculated dose to nearest 500 mg (one-half of 1000-mg tablet).

Adjust dosage up to a maximum of 99 mg/kg per day, administered in 3 divided doses, based on individual patient response and therapeutic goals.

To minimize GI upset when initiating treatment, may start dosage at 45 mg/kg per day and increase weekly by increments of 15 mg/kg per day until full prescribed dose is achieved.

Dosage for 500-mg three times a day tablets: Initial dosage of 75 mg/kg per day (based on actual body weight), administered in 3 divided doses. Round calculated dose to nearest 250 mg (one-half of 500-mg tablet).

Adjust dosage up to a maximum of 99 mg/kg per day, administered in 3 divided doses, based on individual patient response and therapeutic goals.

To minimize GI upset when initiating treatment, may start dosage at 45 mg/kg per day and increase weekly by increments of 15 mg/kg per day until full prescribed dose is achieved.

Dosage of oral solution:Initial dosage of 25 mg/kg (based on actual body weight) 3 times daily (75 mg/kg per day). Round calculated dose to the nearest 2.5 mL.

Adjust dosage up to a maximum of 33 mg/kg 3 times daily (99 mg/kg per day) based on individual patient response and therapeutic goals.

To minimize GI upset when initiating treatment, may start dosage at 45 mg/kg per day and increase weekly by increments of 15 mg/kg per day until full prescribed dose is achieved.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Cautions for Deferiprone

Contraindications

• Known hypersensitivity to deferiprone or any ingredient in the formulation. Hypersensitivity reactions (Henoch-Schönlein purpura, urticaria, and periorbital edema with skin rash) have been reported.

Warnings/Precautions

Warnings

Agranulocytosis and Neutropenia

Risk of agranulocytosis and neutropenia; may result in potentially life-threatening infections and/or death (See Boxed Warning).

Measure ANC before initiating deferiprone. During treatment, monitor ANC weekly for the first 6 months of therapy, once every 2 weeks for the next 6 months of therapy, and every 2–4 weeks (or at the patient’s blood transfusion interval if there have been no interruptions due to any decrease in ANC) after 1 year of therapy. The frequency of ANC monitoring may be reduced by the provider based on an individual patient basis. If infection occurs, interrupt therapy and monitor ANC more frequently.

If neutropenia (ANC <1500/mm³ and >500/mm³) develops, immediately discontinue deferiprone and any other drugs that may cause neutropenia. Obtain CBC, including WBC count corrected for the presence of nucleated RBCs, ANC, and platelet count, daily until neutropenia resolves (ANC ≥1500/mm³).

If agranulocytosis (ANC <500/mm³) develops, discontinue drug and initiate appropriate clinical treatment, including hospitalization if necessary. Do not resume deferiprone unless benefits outweigh risks.

In patients who have experienced neutropenia, do not rechallenge with deferiprone unless benefit outweighs risk.

Other Warnings/Precautions

Liver Enzyme Elevations

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

Zinc Deficiency

Decreased plasma zinc concentrations reported. Monitor serum zinc concentrations at least annually and administer zinc supplements if necessary.

Embryo-Fetal Toxicity

May cause fetal harm; embryofetal deaths and malformations demonstrated in animals. Apprise pregnant women and females of reproductive potential of potential fetal risk.

Specific Populations

Pregnancy

Limited data in pregnant women to inform a drug-associated risk of major birth defects and miscarriage; may cause fetal harm based on evidence of genotoxicity and findings from animal reproduction studies. Apprise pregnant women and females of reproductive potential of the potential risk to the fetus.

Lactation

Not known whether deferiprone is distributed into breastmilk. Effects on breast-fed infants and milk production also unknown. Animal studies have found potential for tumorigenicity in the breast-fed child. Do not breast-feed during treatment with deferiprone and for ≥2 weeks after the last dose.

Females and Males of Reproductive Potential

Pregnancy testing recommended in females of reproductive potential before starting deferiprone. Females of reproductive potential should use an effective method of contraception while taking deferiprone and for ≥6 months after the last dose. Males with female partners of reproductive potential should use effective contraception while taking deferiprone and for ≥3 months after the last dose.

Pediatric Use

Safety and efficacy of deferiprone tablets not established in pediatric patients <8 years of age with chronic iron overload due to blood transfusions.

Safety and efficacy of deferiprone oral solution not established in pediatric patients <3 years of age with chronic iron overload due to blood transfusion.

Geriatric Use

Insufficient number of subjects ≥65 years of age in clinical studies to determine whether geriatric patients respond differently than younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients.

Hepatic Impairment

No clinically significant differences in the pharmacokinetics of deferiprone observed in patients with mild (Child Pugh class A) to moderate (Child Pugh class B) hepatic impairment. Effect of severe (Child Pugh class C) hepatic impairment on the pharmacokinetics of deferiprone unknown.

Renal Impairment

No clinically significant differences in pharmacokinetics of deferiprone observed in patients with mild to severe (eGFR 15–89 mL/minute per 1.73 m²) renal impairment. Effect of end stage renal disease on pharmacokinetics of deferiprone unknown.

Common Adverse Effects

Adverse effects (>6%) in patients with thalassemia: nausea, vomiting, abdominal pain, arthralgia, increased ALT concentrations, neutropenia.

Adverse effects (>6%) in patients with sickle cell disease or other anemias: pyrexia, abdominal pain, bone pain, headache, vomiting, pain in extremity, sickle cell anemia with crisis, back pain, increased ALT concentrations, increased AST concentrations, arthralgia, oropharyngeal pain, nasopharyngitis, decreased neutrophil count, cough, nausea.

Drug Interactions

Metabolized primarily by uridine diphosphate-glucuronosyltransferase (UGT) 1A6. Chelating agent with an affinity for ferric ions (iron III); binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes.

Polyvalent Cations

Deferiprone may bind to polyvalent cations, such as iron, aluminum, and zinc. Allow ≥4 hours between the administration of deferiprone and preparations containing iron, aluminum, or zinc.

Drugs Associated with Neutropenia or Agranulocytosis

Increased risk of neutropenia and agranulocytosis. Avoid concomitant use; if this is not possible, closely monitor ANC.

Drugs Affecting UGT Enzymes

UGT1A6 inhibitors: Pharmacokinetic interaction (decreased glucuronidation of deferiprone). Avoid concomitant use.

Specific Drugs

Deferiprone Pharmacokinetics

Absorption

Bioavailability

After administration of a single dose of deferiprone oral tablet (2 times a day 1000-mg tablet), peak plasma concentrations attained in approximately 2 hours in fasted, healthy subjects.

After administration of a single dose of deferiprone oral tablet (3 times a day 1000-mg tablet or 500-mg tablet) or oral solution, peak plasma concentrations attained in approximately 1 to 2 hours.

Food

Administration of food has no effect on absorption of deferiprone oral tablet (2 times a day formulation); peak plasma concentrations and AUC remain unchanged after a high-fat meal compared to fasted conditions.

Administration of food with deferiprone oral tablet (3 times a day formulation) or oral solution does not result in clinically significant differences in pharmacokinetics.

Special Populations

No clinically significant differences in absorption of deferiprone based on sex, race/ethnicity, body weight, mild to severe renal impairment, or mild to moderate hepatic impairment.

Effects of age, end stage renal disease, or severe hepatic impairment on the absorption of deferiprone unknown.

Distribution

Extent

Not known whether deferiprone is distributed into breastmilk.

Elimination

Metabolism

Extensively metabolized, primarily by UGT1A6. Major metabolite, the 3-O-glucuronide, lacks iron-binding capability.

Elimination Route

Excreted in urine (75–90% within 24 hours following oral administration) mainly as metabolite.

Half-life

Oral tablet (2 times a day formulation): Approximately 1.8 hours.

Oral tablet (3 times a day formulation) or solution: Approximately 2 hours.

Special Populations

No clinically significant differences in elimination based on sex, race/ethnicity, body weight, mild to severe renal impairment, or mild to moderate hepatic impairment.

Effects of age, end stage renal disease, or severe hepatic impairment on elimination of deferiprone unknown.

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted between 15–30°C).

Store 1000 mg (3 times daily formulation) tablets in original bottle, closed tightly to protect from moisture.

Solution

20–25°C (excursions permitted between 15–30°C).

Store in original bottle and carton to protect from light; after first opening bottle, discard any unused portion after 35 days.

Actions

• Chelates iron by binding ferric ions and forming a stable complex.

• Has a high binding affinity for iron in a 3:1 ratio (3 deferiprone molecules binding 1 iron atom) , and a lower binding affinity for other metals, including aluminum and zinc.

Advice to Patients

• Inform patients of the risk of blood disorders, which can result in potentially life-threatening infections. Instruct patients to immediately discontinue the drug and inform clinicians if symptoms of infection (e.g., fever, sore throat, mouth sores, flu-like symptoms) occur. Inform patients of the need for regular monitoring of blood cell counts before and during treatment with deferiprone.

• Inform patients of the risk of abnormal liver enzymes and the need for regular blood testing before and during treatment with deferiprone.

• Inform patients of the risk of zinc deficiency and the need for regular blood testing before and during treatment with deferiprone.

• Advise patients to take the first dose of deferiprone tablets (2 times a day regimen) in the morning and second dose in the evening. Advise patients to avoid alcohol while taking deferiprone tablets (2 times a day).

• Advise patients to take the first dose of deferiprone tablets (3 times a day regimen) in the morning, the second dose at midday, and the third dose in the evening.

• Advise patients to take the first dose of deferiprone oral solution in the morning, the second dose at midday, and the third dose in the evening. Instruct patients to use the provided measuring cup to measure the prescribed dose.

• Advise patients to take a missed dose as soon as it is remembered unless it is almost time for the next dose; a double dose should not be taken to make up for a missed dose. Advise patients to contact their clinician if a higher dosage than prescribed is taken.

• Advise patients to allow for ≥4 hours between taking deferiprone and taking any antacids or mineral supplements that contain iron, aluminum, or zinc.

• Inform patients of the risk of nausea, which may be decreased by taking deferiprone with food.

• Inform patients of the possibility of reddish/brown discoloration of the urine, which is common and not harmful.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Advise pregnant women and females of reproductive potential of the potential risks to the fetus. Advise female patients of reproductive potential to use effective contraception while taking deferiprone and for ≥6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception while taking deferiprone and for ≥3 months after the last dose. Advise female patients not to breast-feed while taking deferiprone and for ≥2 weeks after the last dose.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal or dietary supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of deferiprone is through specialty pharmacy providers. For further information, contact: [Web].

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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