Deferiprone can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. Measure the ANC before starting deferiprone therapy and monitor regularly while on therapy. Interrupt deferiprone therapy if neutropenia develops. Interrupt deferiprone therapy if infection develops and monitor the ANC more frequently. Advise patients taking deferiprone to report immediately any symptoms indicative of infection.
Note: Round dose to the nearest 250 mg (or ½ of 500 mg tablet), 500 mg (or ½ of 1,000 mg tablet), or 2.5 mL (oral solution). If serum ferritin falls consistently below 500 mcg/L, consider temporary treatment interruption until serum ferritin rises above 500 mcg/L. Use actual body weight for dose calculation.
Transfusional iron overload: Oral: Note: Deferiprone is available as an oral solution, a 500 mg tablet, and as 2 different 1,000 mg tablet formulations (a twice-a-day formulation and a 3-times-a-day formulation); verify formulation prior to ordering/dispensing to avoid medication errors.
Initial: 75 mg/kg/day in 2 divided doses (using 1,000 mg twice-a-day tablet formulation only) or in 3 divided doses (using oral solution, 500 mg tablet, or 1,000 mg 3-times-a-day tablet formulation); individualize dose based on response and therapeutic goal. Dosing may start at 45 mg/kg/day and be increased weekly by 15 mg/kg/day increments until 75 mg/kg/day is achieved to minimize GI upset.
Maximum dose: 99 mg/kg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥15 mL/minute/1.73m2: There are no dosage adjustments provided in the manufacturer's labeling. However, no clinically significant pharmacokinetic differences were observed in patients with eGFR 15 to 89 mL/minute/1.73m2.
End stage renal disease: There are no dosage adjustments provided in the manufacturer's labeling (effect is unknown).
Hepatic impairment prior to treatment initiation:
Mild or moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer's labeling. However, no clinically significant pharmacokinetic differences were observed in mild or moderate impairment.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (effect is unknown).
Hepatotoxicity during treatment:
Persistent increase in serum transaminase levels: Consider interruption of therapy.
(For additional information see "Deferiprone: Pediatric drug information")
Note: Deferiprone is available as an oral solution, a 500 mg tablet, and as 2 different 1,000 mg tablet formulations (a twice-a-day formulation and a 3-times-a-day formulation); verify formulation prior to ordering/dispensing to avoid medication errors. Use actual body weight for dose calculations.
Transfusional iron overload, secondary thalassemia syndromes and sickle cell disease: Note: Has been used as monotherapy or in combination with other oral iron chelating agents; patients should be closely monitored for neutropenia; in trials, ANC was assessed weekly or at least prior to every transfusion (Gomber 2018; Maggio 2020; Nazir 2020).
Initial dosing:
Children <8 years: Limited data available in ages <3 years: Oral solution: Oral: 25 mg/kg/dose 3 times daily; round dose to the nearest 250 mg (2.5 mL); may consider a lower dose of 15 mg/kg/dose 3 times a day titrated in 15 mg/kg increments at weekly intervals to minimize GI side effects when initiating therapy (Botzenhardt 2018; Maggio 2020; manufacturer's labeling).
Children ≥8 years and Adolescents:
Three-times-daily dosing:
Oral solution, 3-times-daily 500 mg or 1,000 mg tablet formulations: Oral: Initial: 25 mg/kg/dose 3 times daily; for oral solution, round dose to the nearest 250 mg (2.5 mL); for tablets, round dose to the nearest 1/2 tablet; may consider a lower initial dose of 15 mg/kg/dose 3 times a day titrated in 15 mg/kg increments at weekly intervals to minimize GI side effects when initiating therapy.
Two-times-daily dosing:
Twice-daily 1,000 mg tablet formulation: Oral: Initial: 37.5 mg/kg/dose every 12 hours; round dose to the nearest 500 mg; may consider a lower dose of 22.5 mg/kg/dose every 12 hours titrated in 15 mg/kg increments at weekly intervals to minimize GI side effects when initiating therapy.
Maintenance dosing: Children and Adolescents: Monitor serum ferritin every 2 to 3 months with therapy per the manufacturer; individualize dose based on response and therapeutic goals for hemoglobinopathy; not to exceed maximum daily dose: 99 to 100 mg/kg/day (Maggio 2020; manufacturer's labeling). In DEEP-2 trial, serum ferritin was assessed monthly (Maggio 2020). If serum ferritin falls consistently below 500 mcg/L, consider temporary treatment interruption until serum ferritin rises above 500 mcg/L.
Dosage adjustment for toxicity: Children and Adolescents: Oral:
ANC 500to <1,500/mm3: Interrupt treatment immediately and monitor until recovery; do not rechallenge unless the potential benefit outweighs the risk.
ANC <500/mm3: In addition to treatment interruption, consider hospitalization (and other clinically-appropriate management); do not resume unless the potential benefits outweigh potential risks.
Infection: Interrupt treatment; monitor ANC more frequently.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents: Oral:
eGFR ≥15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied in pediatric patients). However, no clinically significant pharmacokinetic differences were observed in adult patients with eGFR 15 to 89 mL/minute/1.73 m2.
End-stage renal disease: There are no dosage adjustments provided in the manufacturer's labeling (effect is unknown).
Children and Adolescents: Oral:
Baseline hepatic impairment:
Mild or moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied in pediatric patients); however, no clinically significant pharmacokinetic differences were observed in adult patients with mild or moderate impairment; in clinical trials, pediatric patients with ALT >5 × ULN were excluded (Maggio 2020).
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (effect is unknown).
Hepatotoxicity during treatment:
Persistent increase in serum transaminase levels: Consider interruption of therapy; in pediatric clinical trials (DEEP-3), dosage adjustment could be utilized at an AST or ALT >10 × ULN (Maggio 2020).
Refer to adult dosing. Begin at the low end of dosing range.
ANC <1,500/mm3 and >500/mm3: Interrupt treatment immediately and monitor until recovery; do not rechallenge unless the potential benefit outweighs the risk.
ANC <500/mm3: In addition to treatment interruption, consider hospitalization (and other clinically-appropriate management); do not resume unless the potential benefits outweigh potential risks
Infection: Interrupt treatment; monitor ANC more frequently
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Ferriprox: 100 mg/mL (500 mL) [contains fd&c yellow #6 (sunset yellow); cherry-peppermint flavor]
Tablet, Oral:
Ferriprox: 500 mg
Ferriprox: 500 mg [scored]
Ferriprox: 1000 mg
Ferriprox: 1000 mg [scored]
Ferriprox Twice-A-Day: 1000 mg [scored]
Generic: 500 mg, 1000 mg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Ferriprox: 100 mg/mL (500 mL) [contains fd&c yellow #6 (sunset yellow)]
Tablet, Oral:
Ferriprox: 500 mg, 1000 mg
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Ferriprox oral solution: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208030s005lbl.pdf#page=25
Ferriprox tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212269s001lbl.pdf#page=16
Note: Deferiprone is available as an oral solution, a 500 mg tablet, and as 2 different 1,000 mg tablet formulations (a twice-a-day formulation and a 3-times-a-day formulation); verify formulation prior to administration to avoid medication errors.
Oral:
Allow at least a 4-hour interval between deferiprone and medications or supplements containing polyvalent cations (eg, iron, aluminum, zinc).
Oral solution, 500 mg tablet, or 1,000 mg 3-times-a-day tablet formulation: Administer in the morning, at midday, and in the evening. Administration with food may decrease nausea.
1,000 mg twice-a-day tablet formulation: Administer approximately every 12 hours (in the morning and evening) with food to decrease nausea/vomiting.
Note: Deferiprone is available as an oral solution, a 500 mg tablet, and as 2 different 1,000 mg tablet formulations (a twice-a-day formulation and a 3-times-a-day formulation); verify formulation prior to administration to avoid medication errors. Tablets may be halved for necessary dose rounding.
Oral: May consider taking with a meal to decrease nausea. Allow at least a 4-hour interval between deferiprone and medications or supplements containing polyvalent cations (eg, iron, aluminum, zinc).
Oral solution: Administer in the morning, at midday, and in the evening. Measure dose with provided cup; after dose administration, add 10 to 15 mL of water to the cup, swirl around to mix any remaining medication and consume. Hand wash measuring cup after use.
Tablets: Doses should be rounded to nearest half-tablet following verification of appropriate formulation.
Three-times-daily formulation (500 or 1,000 mg): Administer in the morning, at midday, and in the evening.
Twice-daily formulation (1,000 mg): Administer approximately every 12 hours (in the morning and evening).
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
Transfusional iron overload: Treatment of transfusional iron overload in adults and pediatric patients ≥8 years of age (tablets) or adults and pediatric patients ≥3 years of age (oral solution) with thalassemia syndromes, sickle cell disease, or other anemias.
Limitation of use: Safety and effectiveness have not been established for the treatment of transfusional iron overload in patients with myelodysplastic syndrome or Diamond Blackfan anemia.
Deferiprone may be confused with deferoxamine, deferasirox
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Abdominal pain (thalassemia: ≤10%; sickle cell/anemias: 26%), nausea (7% to 13%), vomiting (10% to 19%)
Hepatic: Increased serum alanine aminotransferase (7% to 12%), increased serum aspartate aminotransferase (thalassemia: 1%; sickle cell/anemias: 11%)
Nervous system: Headache (thalassemia: 2%: sickle cell/anemias: 20%)
Neuromuscular and skeletal: Back pain (thalassemia: 2%; sickle cell/anemias: 13%), limb pain (thalassemia: 2%; sickle cell/anemias: 18%), ostealgia (sickle cell/anemias: 25%)
Miscellaneous: Fever (sickle cell/anemias: 28%)
1% to 10%:
Endocrine and metabolic: Weight gain (thalassemia: 2%)
Gastrointestinal: Abdominal distress (thalassemia: ≤10%), decreased appetite (thalassemia: 1%), diarrhea (3% to 5%), dyspepsia (thalassemia: 2%), increased appetite (thalassemia: 4%),
Hematologic & oncologic: Agranulocytosis (2%), neutropenia (6%)
Nervous system: Pain (sickle cell/anemias: 5%)
Neuromuscular and skeletal: Arthralgia (10%), arthropathy (thalassemia: 1%)
Respiratory: Cough (sickle cell/anemias: 8%), nasopharyngitis (sickle cell/anemias: 9%), oropharyngeal pain (sickle cell/anemias: 10%), upper respiratory tract infection (sickle cell/anemias: 5%)
Frequency not defined (all indications):
Endocrine & metabolic: Decreased serum zinc
Genitourinary: Urine discoloration
Postmarketing (all indications):
Cardiovascular: Atrial fibrillation, cardiac failure, hypertension, hypotension, peripheral edema, pulmonary embolism
Dermatologic: Diaphoresis, furuncle, pruritus, pustular rash, skin photosensitivity, skin rash, urticaria
Gastrointestinal: Bruxism, enterocolitis, gastric ulcer, pancreatitis, parotid gland enlargement
Endocrine & metabolic: Dehydration, glycosuria, metabolic acidosis
Genitourinary: Hemoglobinuria, male hypospadias
Hematologic & oncologic: Henoch-Schönlein purpura, pancytopenia, rectal hemorrhage, thrombocythemia
Hepatic: Hepatitis A, hepatomegaly, increased serum bilirubin, jaundice
Hypersensitivity: Anaphylactic shock, hypersensitivity reaction
Infection: Cryptococcosis (cutaneous infection), sepsis, subcutaneous abscess
Nervous system: Abnormal gait, cerebellar syndrome, cerebral hemorrhage, chills, depression, drowsiness, encephalitis (enteroviral), increased intracranial pressure, motor dysfunction (pyramidal tract syndrome), obsessive compulsive disorder, psychomotor impairment, seizure, trismus
Neuromuscular & skeletal: Chondrolysis of articular cartilage, increased creatine phosphokinase in blood specimen, myositis
Ophthalmic: Diplopia, papilledema, periorbital edema, retinal toxicity
Respiratory: Acute respiratory distress syndrome, epistaxis, hemoptysis, pharyngitis, pneumonia
Miscellaneous: Multi-organ failure
Hypersensitivity to deferiprone or any component of the formulation
Canadian labeling: Additional contraindications (not in US labeling): Severe neutropenia (ANC <500/mm3); pregnancy; breastfeeding
Concerns related to adverse effects:
• Agranulocytosis/Neutropenia: May cause agranulocytosis, which could lead to serious infections (some fatal) and may be preceded by neutropenia. If ANC <500/mm3, consider hospitalization (and other clinically appropriate management); do not resume or rechallenge unless the potential benefits outweigh potential risks. Neutropenia and agranulocytosis were generally reversible upon discontinuation. The mechanism for deferiprone-induced agranulocytosis is not known. Avoid concurrent use with other agents associated with neutropenia (or agranulocytosis).
• Hepatotoxicity: Elevations in ALT values have been observed; consider treatment interruption for persistent ALT elevations.
• Hypersensitivity: Hypersensitivity reactions have been reported (eg, Henoch-Schönlein purpura [immunoglobulin A vasculitis], urticaria, and periorbital edema with skin rash).
• Zinc deficiency: Lower plasma zinc concentrations have been observed; supplementation may be needed.
Dosage form specific issues:
• Tablets: Available in 2 different 1,000 mg formulations (a twice-a-day formulation and a 3-times-a-day formulation); each has different identifying characteristics. Ensure the tablet formulation is correct for the dosing regimen prior to prescribing and dispensing to prevent medication errors.
Substrate of UGT1A6, UGT1A9, UGT2B15, UGT2B7
Myelosuppressive Agents: May enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Polyvalent Cation Containing Products: May decrease the serum concentration of Deferiprone. Management: Separate administration of deferiprone and oral medications or supplements that contain polyvalent cations by at least 4 hours. Risk D: Consider therapy modification
UGT1A6 Inhibitors: May increase the serum concentration of Deferiprone. Risk X: Avoid combination
Verify pregnancy status prior to initiation of deferiprone treatment. Females of reproductive potential should use contraception during treatment and for 6 months after the last deferiprone dose. Males with female partners of reproductive potential should use effective contraception during therapy and for 3 months after the last deferiprone dose.
Based on data from animal reproduction studies, in utero exposure to deferiprone may cause fetal harm. Outcome information following deferiprone use in pregnancy is limited. Deferiprone should be discontinued if pregnancy occurs. When iron chelation therapy is needed in a pregnant woman, agents other than deferiprone are preferred (Diamantidis 2016; Origa 2019).
It is not known if deferiprone is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends that women avoid breastfeeding during deferiprone treatment and for 2 weeks after the last dose.
Take with food to decrease nausea/vomiting. Allow at least a 4-hour interval with foods containing iron, aluminum, and zinc.
Serum ferritin (every 2 to 3 months); ANC (at baseline, weekly during the first 6 months of therapy, every 2 weeks for the next 6 months of therapy, and then every 2 to 4 weeks [or at the patient’s blood transfusion interval if an interruption due to any ANC decrease has not occurred] thereafter; reduction in ANC monitoring may be considered on an individual basis); if ANC <1,500/mm3, monitor CBC, WBC (corrected for nucleated RBCs), ANC, and platelets daily until ANC recovery; ALT (at baseline and monthly); zinc levels (at baseline and regularly); signs or symptoms of infection; pregnancy status (prior to initiation and as clinically indicated).
Iron-chelating agent with affinity for ferric ion (iron III); binds to ferric ion and forms a 3:1 (deferiprone:iron) complex which is excreted in the urine. Has a lower affinity for other metals such as copper, aluminum, and zinc.
Absorption: Rapid.
Distribution:
500 mg tablet: 1.6 L/kg.
1,000 mg tablet (twice-a-day formulation): 97 ± 28 L.
Protein binding: <10%.
Metabolism: Primarily by UGT 1A6; major metabolite (3-O-glucuronide) lacks iron-binding capacity.
Half life elimination: ~2 hours.
Time to peak: ~1 to 2 hours.
Excretion: Urine (75% to 90%; primarily as metabolite).
Solution (Ferriprox Oral)
100 mg/mL (per mL): $17.32
Tablets (Deferiprone Oral)
500 mg (per each): $73.81 - $82.26
1000 mg (per each): $174.39
Tablets (Ferriprox Oral)
500 mg (per each): $86.59
1000 mg (per each): $173.18
Tablets (Ferriprox Twice-A-Day Oral)
1000 mg (per each): $233.79
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.