Deferiprone

139.15

139.15

2BTY8KH53L

758880

DTXSID6040666

C73030

Needles from water

V03AC02|V - Various

2933399090

40.5

0.5

White to off-white Crystalline Powder or Needles

1.2±0.1 g/cm3

260-265 °C (decomp)

232.9°C at 760 mmHg

94.5±27.3 °C

1.565

Solubility at 37 deg C: water approx 20 mg/mL (pH 7.4)

-20°C Freezer

1.56X10-4 mm Hg at 25 deg C (est)

LD50 i.p. in rats, mice: 650 mg/kg, 0.8-1.0 g/kg; i.g. in rats: 2.0-3.0 g/kg (Kontoghiorghes, 1995)

Very bitter taste

Henry's Law constant = 1.92X10-8 atm-cu m/mol at 25 °C (est)

3.5|pKa1 = 3.3; pKa2 = 9.7

123.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydrophilic chelator; forms red colored complexes with iron|Hydroxyl radical reaction rate constant = 9.74X10-11 cu cm/molecule-sec at 25 °C (est)

3

22-36/37/38

26-36-37/39

UU7785940

Xn

Stable under recommended storage conditions.

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including deferiprone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 43 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical, or carbon dioxide.|Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.|Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.|Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Agranulocytosis and neutropenia may occur, which can lead to fatal infections. Hepatoxicity is also possible. Most common side effects that lead to discontinuation of therapy were the gastrointestinal adverse effects (diarrhea, ulcer, nausea, gastrointestinal disturbances)|IDENTIFICATION AND USE: Deferiprone is a heavy metal antagonist that chelates iron. It is indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. HUMAN EXPOSURE AND TOXICITY: No cases of acute overdose have been reported. However, 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. At the prescribed dose, deferiprone can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. Based on evidence of genotoxicity and developmental toxicity in animal studies, deferiprone can cause fetal harm when administered to a pregnant woman. ANIMAL STUDIES: Single oral doses of deferiprone of up to 100 mg/kg to mice and rats produced transient hypersalivation, whereas higher doses (300-600 mg/kg) affected behavior, decreased performance and body temperature, and affected passive avoidance and motility. At doses lower than those used clinically, deferiprone has been shown to penetrate the blood brain barrier in rats, and to interfere with dopamine and serotonin metabolism through inhibitory effects on catechol-O-methyltransferase and tyrosine and tryptophan hydroxylases. In a 12-month rodent toxicology study, following administration of deferiprone at doses of 150 or 200 mg/kg/day in 2 divided doses (75 or 100 mg/kg bid), to non-iron-loaded or iron-loaded rats, respectively, 7 of 50 non-iron-loaded and 3 of 50 iron-loaded animals were either found dead or sacrificed moribund with severe anemia and slight to moderate centrilobular degeneration and necrosis. Animals from which blood samples could be collected prior to their unscheduled termination had elevated levels of total bilirubin, aspartate aminotransferase, and/or alanine aminotransferase of up to ca. 8, 4, and 14 times their respective group mean control value. These findings could be ascribed to hypoxia due to severe anemia (hemoglobin concentration <2.5 g/dL). No findings of severe anemia with or without centrilobular degeneration and necrosis, or isolated findings of centrilobular degeneration and necrosis, were noted in non-iron-loaded or iron-loaded survivors. Relatively mild decreases in RBC and WBC counts in surviving rats partially reversed during a 4-week off-dose period following 12 months' treatment; recovery of bone marrow hypocellularity was complete in iron-loaded, but partial in non-iron-loaded, animals. The mean relative weight of the adrenal and pituitary gland was significantly greater in non-iron-loaded rats given 75 mg/kg deferiprone bid as compared to non-iron-loaded untreated rats. Skeletal and soft tissue malformations occurred in offspring of rats and rabbits that received deferiprone orally during organogenesis at the lowest doses tested (25 mg/kg per day in rats; 10 mg/kg per day in rabbits). These doses were equivalent to 3% to 4% of the maximum recommended human dose (MRHD) based on body surface area. No maternal toxicity was evident at these doses. Embryofetal lethality and maternal toxicity occurred in pregnant rabbits given 100 mg/kg/day deferiprone orally during the period of organogenesis. This dose is equivalent to 32% of the MRHD based on body surface area. 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 based on body surface area. Deferiprone was positive in a mouse lymphoma cell assay in vitro. Deferiprone was clastogenic in an in vitro chromosomal 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 pre-dosed with iron dextran were treated with deferiprone. Deferiprone was not mutagenic in the Ames bacterial reverse mutation test.

In large clinical trials, elevations in serum aminotransferase levels occurred in 7.5% of patients treated with deferiprone and led to drug discontinuation in ~1%. In many situations, it was unclear whether the ALT elevations were due to deferiprone therapy as opposed to spontaneous worsening of an underlying chronic hepatitis B or C, which is common in patients with transfusion related iron overload. Furthermore, there have been very few reports of clinically apparent liver injury attributed to deferiprone therapy and the clinical features of hepatic injury from deferiprone (latency to onset, pattern of serum enzyme elevations, clinical symptoms and laboratory findings, subsequent course) have not been defined.

Deferiprone may bind to aluminum. The manufacturer states that an interval of at least 4 hours should be allowed between the administration of deferiprone and aluminum-containing antacids.|Concurrent use of Ferriprox with foods, mineral supplements, and antacids that contain polyvalent cations has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron, aluminum, and zinc), allow at least a 4-hour interval between Ferriprox and other medications (e.g., antacids), or supplements containing these polyvalent cations.|Deferiprone is primarily eliminated via metabolism to the 3-O-glucuronide. In vitro studies suggest that UDP glucuronosyltransferase (UGT) 1A6 is primarily responsible for the glucuronidation of deferiprone which can be reduced up to 78% in the presence of the UGT1A6 inhibitor phenylbutazone. However, the clinical significance of coadministration of Ferriprox with a UGT1A6 inhibitor (e.g. diclofenac, probenecid, or silymarin (milk thistle)) on the systemic exposure of deferiprone has not been determined. Closely monitor patients for adverse reactions that may require downward dose titration or interruption when Ferriprox is concomitantly administered with a UGT1A6 inhibitor.|Avoid concomitant use of Ferriprox with other drugs known to be associated with neutropenia or agranulocytosis; however, if this is not possible, closely monitor the absolute neutrophil count.

LD50 Rat ip 650 mg/kg|LD50 Mouse ip 983 mg/kg|LD50 Rat oral 2000-3000 mg/kg

Given that Ferriprox can be associated with neutropenia and agranulocytosis, therapy in immune-compromised patients should not be initiated unless potential benefits outweigh potential risks.|Based on evidence of genotoxicity and developmental toxicity in animal studies, Ferriprox can cause fetal harm when administered to a pregnant woman. ... If Ferriprox is used during pregnancy or if the patient becomes pregnant while taking Ferriprox, the patient should be apprised of the potential hazard to the fetus.|... Deferiprone /should/ not be prescribed to Diamond-Blackfan anemia (DBA) patients unless the clinical indications are particularly strong, and that the risk of agranulocytosis in thalassemia patients be carefully considered.|The effect of deferiprone on the QT interval has not been studied thoroughly to date; however, torsades de pointes has been reported in a patient with a history of QT-interval prolongation who was receiving deferiprone. The manufacturer states that the drug should be used with caution in patients who may be at increased risk for prolongation of the QT interval (e.g., patients with congestive heart failure, bradycardia, cardiac hypertrophy, hypokalemia, or hypomagnesemia and those receiving diuretics). Patients should be instructed to seek immediate medical attention if symptoms suggestive of an arrhythmia (e.g., palpitations, dizziness, lightheadedness, syncope, seizures) occur.

Plasma protein binding is less than 10%.

Deferiprone is indicated in thalassemia syndromes when first line chelation agents are not adequate to treat transfusional iron overload.|FDA Label|Ferriprox monotherapy is indicated for the treatment of iron overload in patients with thalassaemia major when current chelation therapy is contraindicated or inadequate.Ferriprox in combination with another chelator is indicated in patients with thalassaemia major when monotherapy with any iron chelator is ineffective, or when prevention or treatment of life-threatening consequences of iron overload (mainly cardiac overload) justifies rapid or intensive correction.|Deferiprone Lipomed monotherapy is indicated for the treatment of iron overload in patients with thalassaemia major when current chelation therapy is contraindicated or inadequate.Deferiprone Lipomed in combination with another chelator is indicated in patients with thalassaemia major when monotherapy with any iron chelator is ineffective, or when prevention or treatment of life-threatening consequences of iron overload justifies rapid or intensive correction.|Treatment of chronic iron overload

Deferiprone is an oral iron chelating agent used to treat transfusion related, chronic iron overload. Deferiprone has been linked to a low rate of transient serum aminotransferase elevations during therapy and to rare instances of clinically apparent liver injury.

Hematological Agents

Iron Chelating Agents|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Deferiprone is included in the database.|Ferriprox (deferiprone) is indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. /Included in US product label/|/EXPL THER/ Friedreich ataxia is an inherited disorder characterized by degeneration of the peripheral and central nervous system and hypertrophic cardiomyopathy. Homozygous mutations in the frataxine (FXN) gene reduce expression of frataxin and cause accumulation of iron in the mitochondria. Deferiprone, an oral iron chelator, has been shown effective in cell and animal models of Friedreich ataxia. The results of a 6-month randomized, double blind placebo-controlled study suggested that deferiprone 20 mg/kg/day may reduce disease progression. The authors present their experience of 5 Friedreich ataxia patients treated with deferiprone (20 mg/kg/day), in addition to idebenone treatment, followed over a period of 10-24 months, under off-label authorization. The patients were monitored for laboratory parameters, cardiac assessment, neurological evaluations, and quality of life. The authors conclude that combined therapy of a low dose of deferiprone with idebenone is relatively safe, might improve neurological function, and seems to improve heart hypertrophy, warranting further studies.|/EXPL THER/ Growing body of evidence suggests that Parkinson's disease (PD) is associated with oxidative damage via iron accumulation in the substantia nigra (SN). Low ceruloplasmin (CP)-ferroxidase activity has been identified in the SN and the cerebrospinal fluid (CSF) of patients with PD. The iron chelator, deferiprone, reduces the abnormally high levels of iron in the SN. In order to determine CP's involvement in iron accumulation in SN and PD progression, we aim to compare the ability of iron chelation treatment to reducing both SN iron levels and motor handicap in PD patients according to the level of ceruloplasmin activity. We used a moderate chelation protocol with deferiprone (DFP) based on a, 6-month delayed-start paradigm, randomized placebo controlled clinical trial in 40 PD patients. CP-ferroxidase activity was determined in blood and CSF together with the D544E gene polymorphism (rs701753). Iron levels were determined by R2* MRI sequence and the motor handicap by the UPDRS motor score. After 6 to 12 months of DFP treatment, greater reductions in SN iron levels and UPDRS motor scores were obtained in patients with higher serum and CSF levels of CP-ferroxidase activity. After 6 months of DFP treatment, the AT genotype group displayed greater reduction of iron level in the SN with greater CSF and serum levels of CP activity than the AA genotype group. Although most of the DFP-treated patients displayed clinical and radiological improvements, those with the lower CP activity appeared to respond better to iron chelation. Larger RCTs are now needed to establish whether pharmacological modulation of CP activity could be an innovative neuroprotective strategy in PD.

/BOXED WARNING/ WARNING: AGRANULOCYTOSIS/NEUTROPENIA: Ferriprox can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. Measure the absolute neutrophil count (ANC) before starting Ferriprox therapy and monitor the ANC weekly on therapy. Interrupt Ferriprox therapy if neutropenia develops. Interrupt Ferriprox if infection develops, and monitor the ANC more frequently. Advise patients taking Ferriprox to report immediately any symptoms indicative of infection.|Based on evidence of genotoxicity and developmental toxicity in animal studies, Ferriprox can cause fetal harm when administered to a pregnant woman. ... If Ferriprox is used during pregnancy or if the patient becomes pregnant while taking Ferriprox, the patient should be apprised of the potential hazard to the fetus.|It is not known whether deferiprone is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from Ferriprox, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.|Safety and effectiveness in elderly individuals have not been established. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.|For more Drug Warnings (Complete) data for Deferiprone (13 total), please visit the HSDB record page.

Organic chemicals that form two or more coordination links with an iron ion. Once coordination has occurred, the complex formed is called a chelate. The iron-binding porphyrin group of hemoglobin is an example of a metal chelate found in biological systems. (See all compounds classified as Iron Chelating Agents.)

Deferiprone is absorbed in the upper gastrointestinal tract. Absorption is rapid with maximum plasma concentrations occurring after 1 hour in the fasted state and after 2 hours in the fed state.|Within 5-6 hours of administration, more than 90% of deferiprone is eliminated from the plasma. 75 to 90% of deferiprone is excreted in the urine as the metabolite.|In healthy patients, the volume of distribution is 1L/kg, and in thalassemia patients, the volume of distribution is 1.6L/kg.|In healthy subjects, the mean maximum concentration (Cmax) of deferiprone in serum was 20 ug/mL, and the mean total area under the concentration-time curve (AUC) was 53 ug*hr/mL following oral administration of a 1,500 mg dose of Ferriprox tablets in the fasting state. Dose proportionality over the labeled dosage range of 25 to 33 mg/kg three times per day (75 to 99 mg/kg per day) has not been studied. The elimination half life of deferiprone was 1.9 hours. The accumulation of deferiprone and its glucuronide metabolite at the highest approved dosage level of 33 mg/kg three times per day has not been studied. The volume of distribution of deferiprone is 1.6 L/kg in thalassemia patients, and approximately 1 L/kg in healthy subjects. The plasma protein binding of deferiprone in humans is less than 10%.|Deferiprone is rapidly absorbed from the upper part of the gastrointestinal tract, appearing in the blood within 5 to 10 minutes of oral administration. Peak serum concentrations occur approximately 1 hour after a single dose in fasted healthy subjects and patients, and up to 2 hours after a single dose in the fed state. Administration with food decreased the Cmax of deferiprone by 38% and the AUC by 10%. While a food effect cannot be ruled out, the magnitude of the exposure change does not warrant dose adjustment.|More than 90% of deferiprone is eliminated from plasma within 5 to 6 hours of ingestion. Following oral administration, 75% to 90% is recovered in the urine in the first 24 hours, primarily as metabolite.|/MILK/ It is not known whether deferiprone is excreted in human milk.|For more Absorption, Distribution and Excretion (Complete) data for Deferiprone (8 total), please visit the HSDB record page.

Deferiprone is mainly metabolized by UGT1A6 to the 3-O-glucuronide metabolite. This metabolite cannot chelate iron.|In humans, the majority of the deferiprone is metabolized, primarily by UGT1A6. The contribution of extrahepatic (e.g., renal) UGT1A6 is unknown. The major metabolite of deferiprone is the 3-O-glucuronide, which lacks iron binding capability. Peak serum concentration of the glucuronide occurs 2 to 4 hours after administration of deferiprone in fasting subjects.

The half-life is 1.9 hours.|The pharmacokinetics of deferiprone in children was assessed in 7 patients with thalassemia and iron overload aged 11 to 18 years (mean age= 15 + or - 2.7 years; median=16 years). These patients were on long term therapy with deferiprone and were thus considered to be at steady state. ... Serum levels of deferiprone were maximal approximately 2 hours after dosing and declined with a half-life of 1.8 hours; levels of deferiprone glucuronide peaked at approximately 3 hours and fell with a half-life of 2.0 hours. ...|In healthy subjects ... following oral administration of a 1,500 mg dose of Ferriprox tablets in the fasting state ... the elimination half life ... was 1.9 hours.

Deferiprone is an iron chelator that binds to ferric ions (iron III) and forms a 3:1 (deferiprone:iron) stable complex and is then eliminated in the urine. Deferiprone is more selective for iron in which other metals such as zinc, copper, and aluminum have a lower affinity for deferiprone.|Deferiprone is a chelating agent with an affinity for ferric ion (iron III). Deferiprone binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable over a wide range of pH values. Deferiprone has a lower binding affinity for other metals such as copper, aluminum and zinc than for iron.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ No cases of acute overdose have been reported. ... 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.|/SIGNS AND SYMPTOMS/ Ferriprox can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis.|/CASE REPORTS/ The oral iron chelator deferiprone is associated with various side effects including agranulocytosis, arthropathy, and deranged liver function tests. Rarely, neurological and visual side effects have been reported with high doses. The authors describe rare neurological manifestations of cerebellar ataxia, hypertonia, and bilateral cataract in an 11-year-old boy with thalassemia major on recommended therapeutic doses of deferiprone. The neurological abnormalities resolved with stoppage of deferiprone. Central nervous system toxicity and lenticular opacities may be attributed to the low molecular weight of deferiprone and its ability to cross the blood-brain and blood-ocular barrier, respectively. Clinicians should be alert to the possibility of neurological abnormalities that may occur during deferiprone therapy.|/CASE REPORTS/ A 10-year-old girl with steroid-resistant Diamond-Blackfan anemia (DBA) developed agranulocytosis 9 weeks after chelation with deferiprone was initiated (45 mg/kg daily, 60% of recommended dose) in addition to her ordinary deferoxamine therapy. The blood counts, checked weekly, dropped markedly between weeks 8 and 9. She rapidly developed a septicemia and was admitted with high fever (40.9 degrees C), white blood cell count 0.4 x 10(9)/L, absolute neutrophil count 0.1 x 10(9)/L and platelets 114 x 10(9)/L. She was administered broad spectrum antibiotics, G-CSF (10 ug/kg daily) and corticosteroids but remained neutropenic and died 6 weeks after admission. Bone marrow examination day 23 revealed areas with low cellularity (around 30%), but also areas with infiltrates of T cells; granulopoiesis and erythropoiesis were scarce. We conclude that weekly neutrophil monitoring is not sufficient to avoid fatal agranulocytosis. We suggest that deferiprone not be prescribed to DBA patients unless the clinical indications are particularly strong, and that the risk of agranulocytosis in thalassemia patients be carefully considered.|For more Human Toxicity Excerpts (Complete) data for Deferiprone (11 total), please visit the HSDB record page.

1,2 Dimethyl 3 hydroxy 4 pyridinone

Oral: Tablets, film-coated: 500 mg, Ferriprox, (scored) (ApoPharma)

HLPC determn in serum and urine.

Human drugs -> Ferriprox -> EMA Drug Category|All other therapeutic products -> Human pharmacotherapeutic group|Human drugs -> Deferiprone Lipomed -> EMA Drug Category|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients