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Chiesi USA, Inc. NDC 10122-100-10

Ferriprox (deferiprone) tablets

500 mg

Rx only

100 Tablets


1** INDICATIONS AND USAGE**

FERRIPROX Tablets are indicated for the treatment of transfusional iron overload in adult and pediatric patients 8 years of age and older with thalassemia syndromes, sickle cell disease or other anemias.

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.

5** WARNINGS AND PRECAUTIONS**

5.1Agranulocytosis andNeutropenia

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

Interrupt FERRIPROX if infection develops and monitor the ANC frequently.

Advise patients taking FERRIPROX 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 and 0.5% of patients in pooled clinical trials of 196 patients with sickle cell disease or other anemias. 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 and neutropenia prior to initiating FERRIPROX treatment.

For agranulocytosis (ANC < 0.2 x 109/L) and severe neutropenia (0.2 x 109/L ≤ 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 have developed neutropenia with FERRIPROX unless potential benefits outweigh potential risks.

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).

5.2Liver Enzyme Elevations

In pooled clinical trials, 7.5% of 642 patients with thalassemia syndromes 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. In pooled clinical trials, 7.7% of 196 patients with sickle cell disease or other anemias treated with FERRIPROX developed increased ALT values.

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 [see Dosage and Administration (2.1)].

5.3Zinc Deficiency

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

5.4Embryo-F****etal Toxicity

Based on findings from animal reproduction studies and evidence of genotoxicity, FERRIPROX can cause fetal harm when administered to a pregnant woman. The available data on the use of FERRIPROX 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 FERRIPROX 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 FERRIPROX and for at least three months after the last dose [see Use in Specific Populations (8.1, 8.3)].

6** ADVERSE REACTIONS**

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)]

6.1** Clinical Trial Experience**

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.

FERRIPROX Tablets (twice a day) were evaluated in trials in healthy subjects. FERRIPROX Tablets (twice a day) contain deferiprone, the same active ingredient as FERRIPROX Tablets (deferiprone) (three times a day) and FERRIPROX Oral Solution (deferiprone).

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

Thalassemia Syndromes

The safety of FERRIPROX was evaluated in the pooled clinical trial database [see Clinical Studies (14.1)]. Patients received FERRIPROX Tablets (three times a day) or FERRIPROX Oral Solution . FERRIPROX was administered orally three times a day (total daily dose either 50, 75, or 99 mg/kg), N=642. Among 642 patients receiving FERRIPROX, 492 (76.6%) were exposed for 6 months or longer and 365 (56.9%) were exposed for greater than one year.

The median age of patients who received FERRIPROX was 19 years (range 1, 77 years); 50.2% female; 71.2% White, 17.8% Asian, 9.2% Unknown, 1.2% Multi- racial and 0.6% Black.

The most serious adverse reaction reported in clinical trials with FERRIPROX was agranulocytosis [see Warnings and Precautions (5.1)].

The most common adverse reactions (≥6%) reported during clinical trials were nausea, vomiting, abdominal pain, arthralgia, alanine aminotransferase increased and neutropenia.

The table below lists the adverse drug reactions that occurred in at least 1% of patients treated with FERRIPROX in clinical trials in patients with thalassemia syndromes.

Table 7: Adverse reactions occurring in ≥ 1% of FERRIPROX-treated patients with thalassemia syndromes

Body System	(N=642)
****Adverse Reaction	**%**Patients
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Neutropenia*	7
Agranulocytosis†	1
GASTROINTESTINAL DISORDERS
Nausea	13
Abdominal pain/discomfort	10
Vomiting	10
Diarrhea	3
Dyspepsia	2
INVESTIGATIONS
Alanine aminotransferase increased	7
Weight increased	2
Aspartate aminotransferase increased	1
METABOLISM AND NUTRITION DISORDERS
Increased appetite	4
Decreased appetite	1
MUSCULOSKELETAL AND CONNECTIVE****TISSUE DISORDERS
Arthralgia	10
Back pain	2
Pain in extremity	2
Arthropathy	1
NERVOUS SYSTEM DISORDERS
Headache	2
*Neutropenia includes events of severe neutropenia (ANC ≥0.2 x 109/L and <0.5 x 109/L). †Agranulocytosis (ANC< 0.2 x 109/L)

Gastrointestinal symptoms such as nausea, vomiting, and abdominal pain were the most frequent adverse reactions reported by patients participating in clinical trials and led to the discontinuation of FERRIPROX therapy in 1.6% of patients.

Chromaturia (reddish/brown discoloration of the urine) is a result of the excretion of iron in the urine.

Sickle Cell Disease or Other Anemias

The safety of FERRIPROX compared to deferoxamine was evaluated in LA38-0411 [see Clinical Studies (14.2)]. Patients received FERRIPROX Tablets or FERRIPROX Oral Solution orally three times a day (total daily dose 75-99 mg/kg/day) n=152) or the control arm, deferoxamine, 20-40 mg/kg/day (children) or 40-50 mg/kg/day (adults), by subcutaneous infusion for 5 – 7 days per week, n=76. Among 152 patients receiving FERRIPROX, 120 (78.9%) were exposed for 6 months or longer and 17 (11.2%) were exposed for greater than one year.

The median age of patients who received FERRIPROX was 15 years (range 3, 59 years); 54.6% male; 78.9% White, 15.1% Black and 5.9% Multi-racial.

The most common adverse reactions (≥6%) reported during clinical trials in patients with SCD or other anemias were pyrexia, abdominal pain, bone pain, headache, vomiting, pain in extremity, sickle cell anemia with crisis, back pain, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, arthralgia, oropharyngeal pain, nasopharyngitis, neutrophil count decreased, cough and nausea.

The table below lists the adverse reactions (irrespective of a causal assessment; adverse events) of interest that occurred in patients treated with FERRIPROX in clinical trials in subjects with sickle cell disease or other anemias.

Table 8: Adverse reactions occurring in ≥5% of FERRIPROX-treated patients with sickle cell disease or other anemias

Body System**** ** Adverse Reaction**	FERRIPROX (N=152) % Patients	DEFEROXAMINE (N=76) % Patients
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Sickle cell anemia with crisis	17	13
GASTROINTESTINAL DISORDERS
Abdominal pain*	26	13
Vomiting	19	11
Nausea	7	9
Diarrhea	5	8
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Pyrexia	28	33
Pain	5	4
INFECTIONS AND INFESTATIONS
Nasopharyngitis	9	12
Upper respiratory tract infection	5	3
INVESTIGATIONS
Alanine aminotransferase increased	12	0
Aspartate aminotransferase increased	11	0
Neutrophil count decreased	8	4
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Bone pain	25	34
Pain in extremity	18	15
Back pain	13	18
Arthralgia	10	8
NERVOUS SYSTEM DISORDERS
Headache	20	13
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Oropharyngeal pain	10	15
Cough	8	15

*Grouped term

Clinically relevant adverse reactions in <5% of patients include neutropenia and agranulocytosis.

Pediatric Patients

FERRIPROX has been studied in 86 pediatric patients with sickle cell disease or other anemias. Pediatric patients (<17 years) had an increase in the following adverse reactions as compared to adults: abdominal pain, neutrophil count decreased, bone pain and oropharyngeal pain.

6.2** Postmarketing Experience**

The following additional adverse reactions have been reported in patients receiving FERRIPROX. 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.

14****CLINICAL STUDIES

FERRIPROX Tablets (twice a day) were evaluated in trials in healthy subjects. FERRIPROX Tablets (twice a day) contain deferiprone, the same active ingredient as FERRIPROX Tablets and FERRIPROX Oral Solution. The following information is based on studies with FERRIPROX Tablets (deferiprone) (three times a day) and FERRIPROX Oral Solution (deferiprone).

**14.1Transfusional Iron Overload in Patients with Thalassemia

Syndromes**

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 (35-99 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.

**14.2****Transfusional Iron Overload in Patients with Sickle Cell

DiseaseandotherAnemias**

Study LA38-0411, an actively-controlled non-inferiority study compared the efficacy of FERRIPROX to that of deferoxamine in patients with sickle cell disease and other transfusion-dependent anemias by evaluating liver iron concentration (LIC). The efficacy of FERRIPROX was established based upon the change in LIC from baseline after 12 months of FERRIPROX (75 or 99 mg/kg/day) compared to deferoxamine (20 or 40 mg/kg (pediatric patients); 40 or 50 mg/kg (adult patients)). Patient enrollment was stopped following an interim analysis. After adjusting for the type I (alpha) error, the non-inferiority criterion was established as the upper limit of the 96.01% confidence interval for the difference between treatments being ≤2 mg/g dry weight (dw).

Data from 185 patients (122 on FERRIPROX and 63 on deferoxamine) were available. Among the 122 FERRIPROX treated patients, the mean age was 15.9 years (range 3-46); 57.4% were male; 75.4% were White, 17.2% were Black and 7.4% were Multi-racial; 85% were diagnosed with Sickle Cell Disease and 15% with other anemias. Over 12 months, the Least Squares estimate of mean decrease from baseline in LIC was 4.13 ± 0.50 mg/g dw for FERRIPROX and 4.38 ± 0.59 mg/g dw for deferoxamine, and the non-inferiority criterion was met.

Upon completion of the first year of therapy in the non inferiority study, 89 patients from the FERRIPROX group opted to continue with treatment and 45 from the deferoxamine group opted to switch to ferriprox treatment. This group continued for up to an additional 2 years. LIC continued to decrease over time, with the mean value dropping from 14.93 mg/g dw at baseline to 12.30 mg/g dw after one year of treatment, to 11.19 mg/g dw after two years of treatment, and to 10.45 mg/g dw after three years of treatment.

17** PATIENT COUNSELING INFORMATION**

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

• Instruct patients and their caregivers to store FERRIPROX at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature].

• FERRIPROX Tablets (twice a day), 1,000 mg:
  Advise patients to take the first dose of FERRIPROX Tablets (twice a day) in the morning and the second in the evening.
  Advise patients to take FERRIPROX Tablets (twice a day) with food to reduce the risk of nausea and vomiting.
  Advise patients to avoid alcohol while taking FERRIPROX Tablets (twice a day). Consumption of alcohol while taking FERRIPROX Tablets (twice a day) may result in more rapid release of deferiprone.

• FERRIPROX Tablets (three times a day), 1,000 mg:
  Store in the originally supplied bottle, closed tightly to protect from moisture.
  Advise patients to take the first dose of FERRIPROX in the morning, the second dose at midday, and the third dose in the evening. Clinical experience suggests that taking FERRIPROX with meals may reduce nausea.

• FERRIPROX Tablets, 500 mg:
  Store in the originally supplied bottle, closed tightly to protect from moisture.
  Advise patients to take the first dose of FERRIPROX in the morning, the second dose at midday, and the third dose in the evening. Clinical experience suggests that taking FERRIPROX with meals may reduce nausea.

• If a dose of this medicine has been missed, take it as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Do not catch-up or double doses.

• Inform patients of the risks of developing agranulocytosis and the need for regular blood testing before and during their treatment to monitor for decreases in their ANC. Instruct them to immediately interrupt therapy and report to their physician if they experience any symptoms of infection such as fever, sore throat or flu-like symptoms [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)] in order to check their ANC within 24 hours. Advise them if they are unable to reach their physician, seek care from another provider so as not to delay medical care.

• Inform patients of the risk of abnormal liver transaminases and the need for regular blood testing before and during their treatment to monitor for increases in ALT [see Dosage and Administration (2.1) and Warnings and Precautions (5.2)].

• Inform patients of the risk of zinc deficiency and the need for regular blood testing before and during their treatment to monitor for reductions in zinc [see Dosage and Administration (2.1) and Warnings and Precautions (5.3)].

• Advise patients to contact their physician in the event of overdose.

• Inform patients that their urine might show a reddish/brown discoloration due to the excretion of the iron-deferiprone complex. This is a very common sign of the desired effect, and it is not harmful.

Embryo-Fetal toxicity

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)]. Advise female patients of reproductive potential to use effective contraception during treatment with FERRIPROX and for at least six months after the last dose [see Use in Specific Populations (8.1, 8.3)]. Advise males with female partners of reproductive potential to use effective contraception during treatment with FERRIPROX and for at least three months after the last dose [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].

Lactation

Advise females not to breastfeed during treatment with FERRIPROX and for at least 2 weeks after the last dose [see Use in Specific Populations (8.2)].

Distributed by Chiesi USA, Inc., Cary, NC 27518. Manufactured by Apotex Inc., Toronto, Ontario, Canada, M9L 1T9.

US-618-s1-W

2** DOSAGE AND ADMINISTRATION**

2.1****Important Dosage and Administration Information

FERRIPROX T****abletsare** available in two different 1,000 mg formulations and a 500 mgformulation, which have different oral dosing regimens to achieve the same total daily dosage.**

• FERRIPROX Tablets (twice a day) - 1,000 mg - given two times a day [see Dosage and Administration (2.2)]
• FERRIPROX Tablets (three times a day) - 1,000 mg - given three times a day [see Dosage and Administration (2.3)]
• FERRIPROX 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 FERRIPROX Oral Solution (see the prescribing information for FERRIPROX Oral Solution).

Monitoring for Safety

Due to the risk of agranulocytosis, monitor ANC before and during FERRIPROX therapy.

Test ANC prior to start of FERRIPROX therapy and monitor on the following schedule during treatment:

• First six months of therapy: Monitor ANC weekly;

• Next six months of therapy: Monitor ANC once every two weeks;

• After one year of therapy: Monitor ANC every two to four weeks (or at the patient’s blood transfusion interval in patients that have not experienced an interruption due to any decrease in ANC [see Warnings and Precautions (5.1)].

Due to the risk of hepatic transaminase elevations, monitor ALT before and monthly during FERRIPROX therapy [see Warnings and Precautions (5.2)].

Due to the risk of zinc deficiency, monitor zinc levels before and regularly during FERRIPROX therapy [see Warnings and Precautions (5.3)].

2.2Recommended Dosage for 1,000 mg****FERRIPROX**

Tablets (**twice a day) for Adult and Pediatric Patients with Transfusional Iron Overload due to Thalassemia Syndromes, Sickle Cell Disease or Other Anemias

Starting Dosage for Twice a Day Tablets

The recommended starting oral dosage of FERRIPROX Tablets (twice a day) is 75 mg/kg/day (actual body weight) in two divided doses per day (taken approximately 12 hours apart), with food. Round the total daily dose to the nearest 500 mg (half-tablet). Table 1 describes the number of FERRIPROX Tablets (twice a day) needed to achieve the 75 mg/kg/day total starting daily dosage.

Table1:Number ofFERRIPROX1,000 mg Tablets (twice a day)Needed to Achieve the Total Starting Daily Dosage of 75 mg/kg** (rounded to the nearest half-tablet)**
Body Weight (kg)	Morning	Evening
20	0.5	1
30	1	1.5
40	1.5	1.5
50	2	2
60	2	2.5
70	2.5	3
80	3	3
90	3.5	3.5

To minimize gastrointestinal upset when first starting therapy, dosing can start at 45 mg/kg/day and increase weekly by 15 mg/kg/day increments until the full prescribed dose is achieved.

Dosage Adjustments for Twice a Day Tablets

Tailor dosage adjustments of FERRIPROX Tablets (twice a day) to the individual patient’s response and therapeutic goals (maintenance or reduction of body iron burden). The maximum total daily oral dosage is 99 mg/kg (actual body weight) divided into two doses taken approximately 12 hours apart with food. Table 2 describes the number of FERRIPROX Tablets (twice a day) needed to achieve the 99 mg/day total maximum daily dosage.

Table2:Number of FERRIPROX1,000 mgTablets (twice a day) Needed to Achieve a Total Maximum Recommended Daily Dosage of 99 mg/kg (rounded to the nearest half-tablet)
Body Weight (kg)	Morning	Evening
20	1	1
30	1.5	1.5
40	2	2
50	2.5	2.5
60	3	3
70	3.5	3.5
80	4	4
90	4.5	4.5

2**.3RecommendedDosage for****1,000 mg

FERRIPROX Tablets (three times a day)**** for Adult and Pediatric Patients**** with Transfusional Iron Overload due to Thalassemia Syndromes, Sickle Cell Disease or Other Anemias******

Starting Dosage for Three Times a Day Tablets

The recommended starting oral dosage of FERRIPROX Tablets (three times a day) is 75 mg/kg/day (actual body weight), in three divided doses per day. Table 3 describes the number of FERRIPROX Tablets (three times a day) needed to achieve the 75 mg/kg/day total starting dosage). Round dose to the nearest 500 mg (half-tablet).

Table3:Number ofFERRIPROX1,000 mg Tablets** (three timesaday)Needed to Achieve the Total Starting Daily Dosage of75****mg/kg (rounded to the nearest half-tablet)**
Body Weight (kg)	Morning	Midday	Evening
20	0.5	0.5	0.5
30	1	0.5	1
40	1	1	1
50	1.5	1	1.5
60	1.5	1.5	1.5
70	2	1.5	2
80	2	2	2
90	2.5	2	2.5

To minimize gastrointestinal upset when first starting therapy, dosing can start at 45 mg/kg/day and increase weekly by 15 mg/kg/day increments until the full prescribed dose is achieved.

Dosage Adjustments for Three Times Daily Tablets

Tailor dosage adjustments for FERRIPROX Tablets (three times a day) to the individual patient’s response and therapeutic goals (maintenance or reduction of body iron burden). The maximum oral dosage is 99 mg/kg/day (actual body weight), in three divided doses per day. Table 4 describes the number of FERRIPROX Tablets (three times a day) needed to achieve the 99 mg/day total maximum daily dosage.

**Table 4:**Number of FERRIPROX 1,000 mg Tablets (three times a day) Needed to Achieve the Maximum Total Daily Dosage of 99 mg/kg (rounded to the nearest half-tablet)
Body Weight (kg)	Morning	Midday	Evening
20	0.5	0.5	1
30	1	1	1
40	1.5	1	1.5
50	1.5	1.5	2
60	2	2	2
70	2.5	2	2.5
80	2.5	2.5	3
90	3	3	3

2.4 Recommended Dosage for 500 mg FERRIPROX Tablets** (three

times a day)**** for Adult and Pediatric Patients with Transfusional Iron Overload due to Thalassemia Syndromes, Sickle Cell Disease or Other Anemias**

Starting Dosage for Three Times a Day Tablets

The recommended starting oral dosage of FERRIPROX Tablets (three times a day) is 75 mg/kg/day (actual body weight), in three divided doses per day. Table 5 describes the number of FERRIPROX Tablets (three times a day) needed to achieve the 75 mg/kg/day total starting dosage. Round dose to the nearest 250 mg (half-tablet).

**Table 5:**Number of FERRIPROX 500 mg Tablets (three times a day) Needed to Achieve the Total Starting Daily Dosage of 75 mg/kg dose (rounded to the nearest half-tablet)
Body Weight (kg)	Morning	Midday	Evening
20	1	1	1
30	1.5	1.5	1.5
40	2	2	2
50	2.5	2.5	2.5
60	3	3	3
70	3.5	3.5	3.5
80	4	4	4
90	4.5	4.5	4.5

To minimize gastrointestinal upset when first starting therapy, dosing can start at 45 mg/kg/day and increase weekly by 15 mg/kg/day increments until the full prescribed dose is achieved.

Dosage Adjustments

Tailor dosage adjustments for FERRIPROX Tablets (three times a day) to the individual patient’s response and therapeutic goals (maintenance or reduction of body iron burden). The maximum oral dosage is 99 mg/kg/day (actual body weight), in three divided doses per day. Table 6 describes the number of FERRIPROX Tablets (three times a day) needed to achieve the 99 mg/day total maximum daily dosage.

Table6:Number of FERRIPROX 500 mgTablets (three times a day) NeededtoAchieve the Maximum Total Daily Dosage of 99** mg/kgdose****(rounded to the nearest half-tablet)**
Body Weight (kg)	Morning	Midday	Evening
20	1.5	1	1.5
30	2	2	2
40	3	2	3
50	3.5	3	3.5
60	4	4	4
70	5	4.5	4.5
80	5.5	5	5.5
90	6	6	6

2.5 Monitoring Ferritin Levels to Assess Efficacy

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

2.6Dosage Modification for Drug Interactions

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

11** DESCRIPTION**

FERRIPROX Tablets (deferiprone) 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 C7H9NO2 and 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 - 278 °C.

FERRIPROX Tablets (twice a day), 1,000 mg

White to off-white, capsule-shaped tablets, and imprinted with “FPX” score “DR” on one side and “APO” score “1000” on the other. The tablets can be broken in half along the score line. Each tablet contains 1,000 mg deferiprone and the following inactive ingredients: Tablet core - hypromellose acetate succinate, magnesium oxide, colloidal silicon dioxide and magnesium stearate; Coating - triethyl citrate, talc, titanium dioxide, and methacrylic acid and ethyl acrylate copolymer.

FERRIPROX Tablets (three times a day), 1,000 mg

White to off-white, capsule-shaped tablets, and imprinted with “APO” score “1000” on one side and plain on the other. The tablets can be broken in half along the score line. Each tablet contains 1,000 mg deferiprone and the following inactive ingredients: Tablet core - methylcellulose, crospovidone, and magnesium stearate; Coating - hypromellose, hydroxypropyl cellulose, macrogol, and titanium dioxide.

FERRIPROX Tablets, 500 mg

White to off-white, capsule-shaped tablets, and imprinted with “APO” score “500” on one side and plain on the other. The tablets can be broken in half along the score line. Each tablet contains 500 mg deferiprone and the following inactive ingredients: Tablet core - microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide; Coating - hypromellose, polyethylene glycol, titanium dioxide.

RECENT MAJOR CHANGES

Warnings and Precautions, Agranulocytosis and Neutropenia (5.1)

3/2025