These Highlights Do Not Include All The Information Needed To Use Deferiprone Tablets Safely And Effectively. See Full Prescribing Information For Deferiprone Tablets.

Limitations of Use

• Safety and effectiveness have not been established for the treatment of transfusional iron overload in patients with myelodysplastic syndrome or in patients with Diamond Blackfan anemia.

Pediatric use information is approved for Chiesi USA, Inc.'s FERRIPROX ^®(deferiprone) tablets. However, due to Chiesi USA, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Dispense with Medication Guide available at: https://www.sunpharma.com/usa/products

Pediatric use information is approved for Chiesi USA, Inc.'s FERRIPROX® (deferiprone) tablets. However, due to Chiesi USA, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Revised: April 2025

5230551-0425-03

Warnings and Precautions, Agranulocytosis and Neutropenia (5.1) 3/2025

Store at 20°C to 25°C (68°F to 77°F); [see USP Controlled Room Temperature].

No cases of acute overdose have been reported. There is no specific antidote to deferiprone overdose.

Neurological disorders such as cerebellar symptoms, diplopia, lateral nystagmus, psychomotor slowdown, hand movements and axial hypotonia have been observed in children treated with 2.5 to 3 times the recommended dose for more than one year. The neurological disorders progressively regressed after deferiprone discontinuation.

Deferiprone Tablets contain 1,000 mg or 500 mg deferiprone (3-hydroxy-1,2-dimethylpyridin-4-one), a synthetic, orally active, iron-chelating agent. The molecular formula for deferiprone is C ₇H ₉NO ₂and its molecular weight is 139.15 g/mol. Deferiprone has the following structural formula:

Deferiprone is a white to pinkish-white powder. It is sparingly soluble in deionized water (14.3 mg/mL) and has a melting point range of 272°C to 278°C.

Safety and effectiveness of deferiprone tablets have not been established in pediatric patients with chronic iron overload due to blood transfusions who are less than 8 years of age.

Pediatric use information is approved for Chiesi USA, Inc.'s FERRIPROX® (deferiprone) tablets. However, due to Chiesi USA, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Clinical studies of deferiprone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

The following information is based on studies with deferiprone tablets (three times a day).

Deferiprone is contraindicated in patients with known hypersensitivity to deferiprone or to any of the excipients in the formulations. The following reactions have been reported in association with the administration of deferiprone: Henoch-Schönlein purpura; urticaria; and periorbital edema with skin rash [see Adverse Reactions (6.2)].

Decreased plasma zinc concentrations have been observed on deferiprone therapy. Monitor plasma zinc annually, and supplement in the event of a deficiency [see Dosage and Administration (2.1)].

The following clinically significant adverse reactions are described below and elsewhere in the labeling:

• Agranulocytosis and Neutropenia [see Warnings and Precautions (5.1)]
• Liver Enzyme Elevations [see Warnings and Precautions (5.2)]
• Zinc Deficiency [see Warnings and Precautions (5.3)]

• Drugs Associated with Neutropenia or Agranulocytosis: Avoid co-administration. If co-administration is unavoidable, closely monitor the absolute neutrophil count. ( 7.1)
• UGT1A6 Inhibitors: Avoid co-administration. ( 7.2)
• Polyvalent Cations: Allow at least a 4-hour interval between administration of deferiprone and drugs or supplements containing polyvalent cations (e.g., iron, aluminum, or zinc). ( 2.6, 7.2)

No clinical studies were performed to assess the relationship between the dose of deferiprone and the amount of iron eliminated from the body.

Deferiprone tablets are indicated for the treatment of transfusional iron overload in adult patients with thalassemia syndromes when current chelation therapy is inadequate.

Deferiprone is a chelating agent with an affinity for ferric ions (iron III). Deferiprone binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable at physiological pH.

Based on findings from animal reproduction studies and evidence of genotoxicity, deferiprone can cause fetal harm when administered to a pregnant woman. The available data on the use of deferiprone in pregnant women are insufficient to inform risk. In animal studies, administration of deferiprone during the period of organogenesis resulted in embryo-fetal death and malformations at doses lower than equivalent human clinical doses. Advise pregnant women and females of reproductive potential of the potential risk to the fetus [see Use in Specific Populations (8.1)] .

Advise females of reproductive potential to use an effective method of contraception during treatment with deferiprone and for at least six months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with deferiprone and for at least three months after the last dose [see Use in Specific Populations (8.1, 8.3)].

• Liver Enzyme Elevations: Monitor monthly and discontinue for persistent elevations. ( 5.2)
• Zinc Deficiency: Monitor during therapy and supplement for deficiency. ( 5.3)
• Embryo-Fetal Toxicity: Can cause fetal harm. ( 5.4)

• Deferiprone tablets are available in two formulations. A 1,000 mg formulation and a 500 mg formulation, which have different dosing regimens to achieve the same total daily dosage. ( 2.1)
• To prevent medication errors, before prescribing and dispensing, ensure that the tablet formulation is appropriate for the dosing regimen. Each tablet has distinct identifying characteristics. ( 2.1, 3)
• Deferiprone tablets (three times a day), 1,000 mg:
  • Starting oral dosage: 75 mg/kg/day (actual body weight) in three divided doses ( 2.3)
  • Maximum oral dosage: 99 mg/kg/day (actual body weight) in three divided doses ( 2.3)
• Deferiprone tablets (three times a day), 500 mg:
  • Starting oral dosage: 75 mg/kg/day (actual body weight) in three divided doses ( 2.4)
  • Maximum oral dosage: 99 mg/kg/day (actual body weight) in three divided doses ( 2.4)

In pooled clinical trials, 7.5% of 642 patients with thalassemia syndromes treated with deferiprone developed increased ALT values. Four (0.62%) deferiprone-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 deferiprone and consider interruption of therapy if there is a persistent increase in the serum transaminase levels [see Dosage and Administration (2.1)] .

• Tablets (three times a day): 1,000 mg are white, film-coated, oval shaped tablets; imprinted with "T" score "1 K" on one side and plain on the other side.
• Tablets: 500 mg are white to pinkish-white, capsule-shaped tablets; scored on one side, engraved "T" on the left of the score line and "5" on the right and plain on the other side.

The following additional adverse reactions have been reported in patients receiving deferiprone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.

Blood and lymphatic system disorders:thrombocytosis, pancytopenia.

Cardiac disorders:atrial fibrillation, cardiac failure.

Congenital, familial and genetic disorders:hypospadias.

Eye disorders:diplopia, papilledema, retinal toxicity.

Gastrointestinal disorders:enterocolitis, rectal hemorrhage, gastric ulcer, pancreatitis, parotid gland enlargement.

General disorders and administration site conditions:chills, edema peripheral, multi-organ failure.

Hepatobiliary disorders:jaundice, hepatomegaly.

Immune system disorders:anaphylactic shock, hypersensitivity.

Infections and infestations:cryptococcal cutaneous infection, enteroviral encephalitis, pharyngitis, pneumonia, sepsis, furuncle, infectious hepatitis, rash pustular, subcutaneous abscess.

Investigations:blood bilirubin increased, blood creatinine phosphokinase increased.

Metabolism and nutrition disorders:metabolic acidosis, dehydration.

Musculoskeletal and connective tissue disorders:myositis, chondropathy, trismus.

Nervous system disorders:cerebellar syndrome, cerebral hemorrhage, convulsion, gait disturbance, intracranial pressure increased, psychomotor skills impaired, pyramidal tract syndrome, somnolence.

Psychiatric disorders:bruxism, depression, obsessive-compulsive disorder.

Renal disorders:glycosuria, hemoglobinuria.

Respiratory, thoracic and mediastinal disorders:acute respiratory distress syndrome, epistaxis, hemoptysis, pulmonary embolism.

Skin, subcutaneous tissue disorders:hyperhidrosis, periorbital edema, photosensitivity reaction, pruritis, urticaria, rash, Henoch-Schönlein purpura.

Vascular disorders:hypotension, hypertension.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reaction information represents the pooled data collected from single arm or active-controlled clinical trials with deferiprone tablets (three times a day).

Lactation: Advise not to breastfeed. ( 8.2)

 

Pediatric use information is approved for Chiesi USA, Inc.'s FERRIPROX® (deferiprone) tablets. However, due to Chiesi USA, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Advise the patient to read the FDA-approved patient labeling (Medication Guide)

Fatal agranulocytosis can occur with deferiprone use. Deferiprone can also cause neutropenia, which may foreshadow agranulocytosis. Measure the absolute neutrophil count (ANC) before starting deferiprone therapy and monitor it regularly while on therapy [see Dosage and Administration (2.1)] .

Reduction in the frequency of ANC monitoring should be considered on an individual patient basis, according to the health care provider's assessment of the patient's understanding of the risk minimization measures required during therapy.

Interrupt deferiprone therapy if neutropenia develops (ANC < 1.5 × 10 ⁹/L).

Interrupt deferiprone if infection develops and monitor the ANC frequently.

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

The incidence of agranulocytosis was 1% of patients in pooled clinical trials of 642 patients with thalassemia syndromes. The mechanism of deferiprone-associated agranulocytosis is unknown. Agranulocytosis and neutropenia usually resolve upon discontinuation of deferiprone, but there have been reports of agranulocytosis leading to death.

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

• Deferiprone can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. [see Warnings and Precautions (5.1)]
• Measure the absolute neutrophil count (ANC) before starting deferiprone therapy and monitor regularly while on therapy.
• Interrupt deferiprone therapy if neutropenia develops. [see Warnings and Precautions (5.1)]
• Interrupt deferiprone if infection develops, and monitor the ANC more frequently. [see Warnings and Precautions (5.1)]
• Advise patients taking deferiprone to report immediately any symptoms indicative of infection. [see Warnings and Precautions (5.1)]

Allow at least a 4-hour interval between administration of deferiprone and other drugs or supplements containing polyvalent cations such as iron, aluminum, or zinc [see Drug Interactions (7.2), Clinical Pharmacology (12.3)] .

Monitor serum ferritin concentration every two to three months to assess the effect of deferiprone on body iron stores. If the serum ferritin is consistently below 500 mcg/L, consider temporarily interrupting deferiprone therapy until serum ferritin rises above 500 mcg/L.

Deferiprone tablets are available in a 1,000 mg formulation and a 500 mg formulation, which have different oral dosing regimens to achieve the same total daily dosage.

• Deferiprone tablets (three times a day) - 1,000 mg - given three times a day [see Dosage and Administration (2.3)]
• Deferiprone tablets - 500 mg - given three times a day [see Dosage and Administration (2.4)]

To prevent medication errors, before prescribing and dispensing, ensure that the tablet formulation is appropriate for the dosing regimen. Each tablet has distinct identifying characteristics [see Dosage Forms and Strengths (3)].

For patients who have trouble swallowing tablets, consider the use of oral solution (see the prescribing information for oral solution).

Deferiprone

Tablets 500 mg

PHARMACIST: Dispense Medication Guide to each patient.

Print Medication Guides at: www.taro.com

TARO

Rx only

NDC 51672-4237-4

50 Tablets

THREE-TIMES-A-DAY

Deferiprone

Tablets 1,000 mg

Attention Pharmacist: Dispense the accompanying

Medication Guide to each patient.

TARO

Rx only

Avoid co-administration of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis. If co-administration is unavoidable, closely monitor the absolute neutrophil count [see Warnings and Precautions (5.1)] .

Carcinogenicity studies have not been conducted with deferiprone. However, in view of the genotoxicity results, and the findings of mammary gland hyperplasia and mammary gland tumors in rats treated with deferiprone in the 52-week toxicology study, tumor formation in carcinogenicity studies must be regarded as likely.

Deferiprone was positive in a mouse lymphoma cell assay in vitro. Deferiprone was clastogenic in an in vitrochromosomal aberration test in mice and in a chromosomal aberration test in Chinese Hamster Ovary cells. Deferiprone given orally or intraperitoneally was clastogenic in a bone marrow micronucleus assay in non-iron-loaded mice. A micronucleus test was also positive when mice predosed with iron dextran were treated with deferiprone. Deferiprone was not mutagenic in the Ames bacterial reverse mutation test.

A fertility and early embryonic development study of deferiprone was conducted in rats. Sperm counts, motility and morphology were unaffected by treatment with deferiprone. There were no effects observed on male or female fertility or reproductive function at the highest dose which was 25% of the MRHD.

In a prospective, planned, pooled analysis of patients with thalassemia syndromes from several studies, the efficacy of deferiprone was assessed in transfusion-dependent iron overload patients in whom previous iron chelation therapy had failed or was considered inadequate due to poor tolerance. The main criterion for chelation failure was serum ferritin > 2,500 mcg/L before treatment with deferiprone. Deferiprone therapy (35 to 99 mg/kg/day) was considered successful in individual patients who experienced a ≥ 20% decline in serum ferritin within one year of starting therapy.

Data from a total of 236 patients were analyzed. Of the 224 patients with thalassemia who received deferiprone monotherapy and were eligible for serum ferritin analysis, 105 (47%) were male and 119 (53%) were female. The mean age of these patients was 18.2 years (range 2 to 62; 91 patients were <17).

For the patients in the analysis, the endpoint of at least a 20% reduction in serum ferritin was met in 50% (of 236 subjects), with a 95% confidence interval of 43% to 57%.

A small number of patients with thalassemia and iron overload were assessed by measuring the change in the number of milliseconds (ms) in the cardiac MRI T2* value before and after treatment with deferiprone for one year. There was an increase in cardiac MRI T2* from a mean at baseline of 11.8 ± 4.9 ms to a mean of 15.1 ± 7.0 ms after approximately one year of treatment. The clinical significance of this observation is not known.

Limitations of Use

• Safety and effectiveness have not been established for the treatment of transfusional iron overload in patients with myelodysplastic syndrome or in patients with Diamond Blackfan anemia.

Pediatric use information is approved for Chiesi USA, Inc.'s FERRIPROX ^®(deferiprone) tablets. However, due to Chiesi USA, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Dispense with Medication Guide available at: https://www.sunpharma.com/usa/products

Pediatric use information is approved for Chiesi USA, Inc.'s FERRIPROX® (deferiprone) tablets. However, due to Chiesi USA, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Revised: April 2025

5230551-0425-03

Warnings and Precautions, Agranulocytosis and Neutropenia (5.1) 3/2025

Store at 20°C to 25°C (68°F to 77°F); [see USP Controlled Room Temperature].

No cases of acute overdose have been reported. There is no specific antidote to deferiprone overdose.

Neurological disorders such as cerebellar symptoms, diplopia, lateral nystagmus, psychomotor slowdown, hand movements and axial hypotonia have been observed in children treated with 2.5 to 3 times the recommended dose for more than one year. The neurological disorders progressively regressed after deferiprone discontinuation.

Deferiprone Tablets contain 1,000 mg or 500 mg deferiprone (3-hydroxy-1,2-dimethylpyridin-4-one), a synthetic, orally active, iron-chelating agent. The molecular formula for deferiprone is C ₇H ₉NO ₂and its molecular weight is 139.15 g/mol. Deferiprone has the following structural formula:

Deferiprone is a white to pinkish-white powder. It is sparingly soluble in deionized water (14.3 mg/mL) and has a melting point range of 272°C to 278°C.

Safety and effectiveness of deferiprone tablets have not been established in pediatric patients with chronic iron overload due to blood transfusions who are less than 8 years of age.

Pediatric use information is approved for Chiesi USA, Inc.'s FERRIPROX® (deferiprone) tablets. However, due to Chiesi USA, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Clinical studies of deferiprone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

The following information is based on studies with deferiprone tablets (three times a day).

Deferiprone is contraindicated in patients with known hypersensitivity to deferiprone or to any of the excipients in the formulations. The following reactions have been reported in association with the administration of deferiprone: Henoch-Schönlein purpura; urticaria; and periorbital edema with skin rash [see Adverse Reactions (6.2)].

Decreased plasma zinc concentrations have been observed on deferiprone therapy. Monitor plasma zinc annually, and supplement in the event of a deficiency [see Dosage and Administration (2.1)].

The following clinically significant adverse reactions are described below and elsewhere in the labeling:

• Agranulocytosis and Neutropenia [see Warnings and Precautions (5.1)]
• Liver Enzyme Elevations [see Warnings and Precautions (5.2)]
• Zinc Deficiency [see Warnings and Precautions (5.3)]

• Drugs Associated with Neutropenia or Agranulocytosis: Avoid co-administration. If co-administration is unavoidable, closely monitor the absolute neutrophil count. ( 7.1)
• UGT1A6 Inhibitors: Avoid co-administration. ( 7.2)
• Polyvalent Cations: Allow at least a 4-hour interval between administration of deferiprone and drugs or supplements containing polyvalent cations (e.g., iron, aluminum, or zinc). ( 2.6, 7.2)

No clinical studies were performed to assess the relationship between the dose of deferiprone and the amount of iron eliminated from the body.

Deferiprone tablets are indicated for the treatment of transfusional iron overload in adult patients with thalassemia syndromes when current chelation therapy is inadequate.

Deferiprone is a chelating agent with an affinity for ferric ions (iron III). Deferiprone binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable at physiological pH.

Based on findings from animal reproduction studies and evidence of genotoxicity, deferiprone can cause fetal harm when administered to a pregnant woman. The available data on the use of deferiprone in pregnant women are insufficient to inform risk. In animal studies, administration of deferiprone during the period of organogenesis resulted in embryo-fetal death and malformations at doses lower than equivalent human clinical doses. Advise pregnant women and females of reproductive potential of the potential risk to the fetus [see Use in Specific Populations (8.1)] .

Advise females of reproductive potential to use an effective method of contraception during treatment with deferiprone and for at least six months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with deferiprone and for at least three months after the last dose [see Use in Specific Populations (8.1, 8.3)].

• Liver Enzyme Elevations: Monitor monthly and discontinue for persistent elevations. ( 5.2)
• Zinc Deficiency: Monitor during therapy and supplement for deficiency. ( 5.3)
• Embryo-Fetal Toxicity: Can cause fetal harm. ( 5.4)

• Deferiprone tablets are available in two formulations. A 1,000 mg formulation and a 500 mg formulation, which have different dosing regimens to achieve the same total daily dosage. ( 2.1)
• To prevent medication errors, before prescribing and dispensing, ensure that the tablet formulation is appropriate for the dosing regimen. Each tablet has distinct identifying characteristics. ( 2.1, 3)
• Deferiprone tablets (three times a day), 1,000 mg:
  • Starting oral dosage: 75 mg/kg/day (actual body weight) in three divided doses ( 2.3)
  • Maximum oral dosage: 99 mg/kg/day (actual body weight) in three divided doses ( 2.3)
• Deferiprone tablets (three times a day), 500 mg:
  • Starting oral dosage: 75 mg/kg/day (actual body weight) in three divided doses ( 2.4)
  • Maximum oral dosage: 99 mg/kg/day (actual body weight) in three divided doses ( 2.4)

In pooled clinical trials, 7.5% of 642 patients with thalassemia syndromes treated with deferiprone developed increased ALT values. Four (0.62%) deferiprone-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 deferiprone and consider interruption of therapy if there is a persistent increase in the serum transaminase levels [see Dosage and Administration (2.1)] .

• Tablets (three times a day): 1,000 mg are white, film-coated, oval shaped tablets; imprinted with "T" score "1 K" on one side and plain on the other side.
• Tablets: 500 mg are white to pinkish-white, capsule-shaped tablets; scored on one side, engraved "T" on the left of the score line and "5" on the right and plain on the other side.

The following additional adverse reactions have been reported in patients receiving deferiprone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.

Blood and lymphatic system disorders:thrombocytosis, pancytopenia.

Cardiac disorders:atrial fibrillation, cardiac failure.

Congenital, familial and genetic disorders:hypospadias.

Eye disorders:diplopia, papilledema, retinal toxicity.

Gastrointestinal disorders:enterocolitis, rectal hemorrhage, gastric ulcer, pancreatitis, parotid gland enlargement.

General disorders and administration site conditions:chills, edema peripheral, multi-organ failure.

Hepatobiliary disorders:jaundice, hepatomegaly.

Immune system disorders:anaphylactic shock, hypersensitivity.

Infections and infestations:cryptococcal cutaneous infection, enteroviral encephalitis, pharyngitis, pneumonia, sepsis, furuncle, infectious hepatitis, rash pustular, subcutaneous abscess.

Investigations:blood bilirubin increased, blood creatinine phosphokinase increased.

Metabolism and nutrition disorders:metabolic acidosis, dehydration.

Musculoskeletal and connective tissue disorders:myositis, chondropathy, trismus.

Nervous system disorders:cerebellar syndrome, cerebral hemorrhage, convulsion, gait disturbance, intracranial pressure increased, psychomotor skills impaired, pyramidal tract syndrome, somnolence.

Psychiatric disorders:bruxism, depression, obsessive-compulsive disorder.

Renal disorders:glycosuria, hemoglobinuria.

Respiratory, thoracic and mediastinal disorders:acute respiratory distress syndrome, epistaxis, hemoptysis, pulmonary embolism.

Skin, subcutaneous tissue disorders:hyperhidrosis, periorbital edema, photosensitivity reaction, pruritis, urticaria, rash, Henoch-Schönlein purpura.

Vascular disorders:hypotension, hypertension.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reaction information represents the pooled data collected from single arm or active-controlled clinical trials with deferiprone tablets (three times a day).

Lactation: Advise not to breastfeed. ( 8.2)

 

Pediatric use information is approved for Chiesi USA, Inc.'s FERRIPROX® (deferiprone) tablets. However, due to Chiesi USA, Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Advise the patient to read the FDA-approved patient labeling (Medication Guide)

Fatal agranulocytosis can occur with deferiprone use. Deferiprone can also cause neutropenia, which may foreshadow agranulocytosis. Measure the absolute neutrophil count (ANC) before starting deferiprone therapy and monitor it regularly while on therapy [see Dosage and Administration (2.1)] .

Reduction in the frequency of ANC monitoring should be considered on an individual patient basis, according to the health care provider's assessment of the patient's understanding of the risk minimization measures required during therapy.

Interrupt deferiprone therapy if neutropenia develops (ANC < 1.5 × 10 ⁹/L).

Interrupt deferiprone if infection develops and monitor the ANC frequently.

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

The incidence of agranulocytosis was 1% of patients in pooled clinical trials of 642 patients with thalassemia syndromes. The mechanism of deferiprone-associated agranulocytosis is unknown. Agranulocytosis and neutropenia usually resolve upon discontinuation of deferiprone, but there have been reports of agranulocytosis leading to death.

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

• Deferiprone can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. [see Warnings and Precautions (5.1)]
• Measure the absolute neutrophil count (ANC) before starting deferiprone therapy and monitor regularly while on therapy.
• Interrupt deferiprone therapy if neutropenia develops. [see Warnings and Precautions (5.1)]
• Interrupt deferiprone if infection develops, and monitor the ANC more frequently. [see Warnings and Precautions (5.1)]
• Advise patients taking deferiprone to report immediately any symptoms indicative of infection. [see Warnings and Precautions (5.1)]

Allow at least a 4-hour interval between administration of deferiprone and other drugs or supplements containing polyvalent cations such as iron, aluminum, or zinc [see Drug Interactions (7.2), Clinical Pharmacology (12.3)] .

Monitor serum ferritin concentration every two to three months to assess the effect of deferiprone on body iron stores. If the serum ferritin is consistently below 500 mcg/L, consider temporarily interrupting deferiprone therapy until serum ferritin rises above 500 mcg/L.

Deferiprone tablets are available in a 1,000 mg formulation and a 500 mg formulation, which have different oral dosing regimens to achieve the same total daily dosage.

• Deferiprone tablets (three times a day) - 1,000 mg - given three times a day [see Dosage and Administration (2.3)]
• Deferiprone tablets - 500 mg - given three times a day [see Dosage and Administration (2.4)]

To prevent medication errors, before prescribing and dispensing, ensure that the tablet formulation is appropriate for the dosing regimen. Each tablet has distinct identifying characteristics [see Dosage Forms and Strengths (3)].

For patients who have trouble swallowing tablets, consider the use of oral solution (see the prescribing information for oral solution).

Deferiprone

Tablets 500 mg

PHARMACIST: Dispense Medication Guide to each patient.

Print Medication Guides at: www.taro.com

TARO

Rx only

NDC 51672-4237-4

50 Tablets

THREE-TIMES-A-DAY

Deferiprone

Tablets 1,000 mg

Attention Pharmacist: Dispense the accompanying

Medication Guide to each patient.

TARO

Rx only

Avoid co-administration of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis. If co-administration is unavoidable, closely monitor the absolute neutrophil count [see Warnings and Precautions (5.1)] .

Carcinogenicity studies have not been conducted with deferiprone. However, in view of the genotoxicity results, and the findings of mammary gland hyperplasia and mammary gland tumors in rats treated with deferiprone in the 52-week toxicology study, tumor formation in carcinogenicity studies must be regarded as likely.

Deferiprone was positive in a mouse lymphoma cell assay in vitro. Deferiprone was clastogenic in an in vitrochromosomal aberration test in mice and in a chromosomal aberration test in Chinese Hamster Ovary cells. Deferiprone given orally or intraperitoneally was clastogenic in a bone marrow micronucleus assay in non-iron-loaded mice. A micronucleus test was also positive when mice predosed with iron dextran were treated with deferiprone. Deferiprone was not mutagenic in the Ames bacterial reverse mutation test.

A fertility and early embryonic development study of deferiprone was conducted in rats. Sperm counts, motility and morphology were unaffected by treatment with deferiprone. There were no effects observed on male or female fertility or reproductive function at the highest dose which was 25% of the MRHD.

In a prospective, planned, pooled analysis of patients with thalassemia syndromes from several studies, the efficacy of deferiprone was assessed in transfusion-dependent iron overload patients in whom previous iron chelation therapy had failed or was considered inadequate due to poor tolerance. The main criterion for chelation failure was serum ferritin > 2,500 mcg/L before treatment with deferiprone. Deferiprone therapy (35 to 99 mg/kg/day) was considered successful in individual patients who experienced a ≥ 20% decline in serum ferritin within one year of starting therapy.

Data from a total of 236 patients were analyzed. Of the 224 patients with thalassemia who received deferiprone monotherapy and were eligible for serum ferritin analysis, 105 (47%) were male and 119 (53%) were female. The mean age of these patients was 18.2 years (range 2 to 62; 91 patients were <17).

For the patients in the analysis, the endpoint of at least a 20% reduction in serum ferritin was met in 50% (of 236 subjects), with a 95% confidence interval of 43% to 57%.

A small number of patients with thalassemia and iron overload were assessed by measuring the change in the number of milliseconds (ms) in the cardiac MRI T2* value before and after treatment with deferiprone for one year. There was an increase in cardiac MRI T2* from a mean at baseline of 11.8 ± 4.9 ms to a mean of 15.1 ± 7.0 ms after approximately one year of treatment. The clinical significance of this observation is not known.