CLASSES

Antidotes, Systemic
Chelating Agents

BOXED WARNING

Deferiprone may cause agranulocytosis which can lead to serious infection and death. Neutropenia may precede the development of agranulocytosis. Neutropenia and agranulocytosis usually resolve after discontinuation of therapy; however, there have been fatal cases of agranulocytosis associated with deferiprone. The mechanism for agranulocytosis due to the drug is not known. The absolute neutrophil count (ANC) should be monitored prior to initiation of deferiprone and regularly during therapy according to the following schedule: monitor ANC weekly during the first 6 months of therapy, monitor ANC every 2 weeks during the next 6 months of therapy, and monitor ANC every 2 to 4 weeks (or at the patient's blood transfusion interval in patients that have not experienced an interruption due to any decrease in ANC) after 1 year of therapy. 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 (i.e., ANC between 0.5 to 1.5 x 109/L) and obtain a complete blood cell (CBC) count, an ANC, and a platelet count daily until the white blood cell (WBC) count recovers. If agranulocytosis develops (i.e., ANC less than 0.5 x 109/L), consider hospitalization and other management as clinically appropriate. Do not resume deferiprone therapy in patients who develop agranulocytosis unless potential benefits outweigh potential risks. Do not rechallenge patients who have developed neutropenia unless potential benefits outweigh potential risks. Therapy should also be interrupted if an infection develops, and the ANC should then be monitored more frequently. Advise patients to immediately interrupt therapy and talk to their health care provider if they experience any symptoms of infection (e.g., fever, chills, sore throat, mouth sores, or flu-like symptoms).[46163] [60360]

DEA CLASS

Rx

DESCRIPTION

Iron chelator
Used for transfusional iron overload due to thalassemia syndromes, sickle cell disease, or other anemias in adults and pediatric patients 3 years and older
May cause agranulocytosis

COMMON BRAND NAMES

Ferriprox

HOW SUPPLIED

Deferiprone/Ferriprox Oral Sol: 1mL, 100mg
Deferiprone/Ferriprox Oral Tab: 500mg, 1000mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

99 mg/kg/day PO.

99 mg/kg/day PO.

99 mg/kg/day PO.

3 to 12 years: 99 mg/kg/day PO.
1 to 2 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are necessary.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are necessary.

ADMINISTRATION

NOTE: The 1,000 mg tablets are available in 2 different formulations, which have different dosing regimens to achieve the same total daily dosage (i.e., a twice a day tablet and 3 times a day tablet). Each tablet has different identifying characteristics to prevent medication errors. Before prescribing and dispensing a 1,000 mg tablet, ensure the formulation is appropriate for the dosing regimen.
Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.

STORAGE

Ferriprox:
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in the original carton to protect from light
- Store opened container at room temperature (between 59 to 86 degrees F) for up to 35 days

CONTRAINDICATIONS / PRECAUTIONS

Deferiprone is contraindicated in patients with a hypersensitivity to deferiprone or any excipients in the formulation.

Deferiprone may cause agranulocytosis which can lead to serious infection and death. Neutropenia may precede the development of agranulocytosis. Neutropenia and agranulocytosis usually resolve after discontinuation of therapy; however, there have been fatal cases of agranulocytosis associated with deferiprone. The mechanism for agranulocytosis due to the drug is not known. The absolute neutrophil count (ANC) should be monitored prior to initiation of deferiprone and regularly during therapy according to the following schedule: monitor ANC weekly during the first 6 months of therapy, monitor ANC every 2 weeks during the next 6 months of therapy, and monitor ANC every 2 to 4 weeks (or at the patient's blood transfusion interval in patients that have not experienced an interruption due to any decrease in ANC) after 1 year of therapy. 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 (i.e., ANC between 0.5 to 1.5 x 109/L) and obtain a complete blood cell (CBC) count, an ANC, and a platelet count daily until the white blood cell (WBC) count recovers. If agranulocytosis develops (i.e., ANC less than 0.5 x 109/L), consider hospitalization and other management as clinically appropriate. Do not resume deferiprone therapy in patients who develop agranulocytosis unless potential benefits outweigh potential risks. Do not rechallenge patients who have developed neutropenia unless potential benefits outweigh potential risks. Therapy should also be interrupted if an infection develops, and the ANC should then be monitored more frequently. Advise patients to immediately interrupt therapy and talk to their health care provider if they experience any symptoms of infection (e.g., fever, chills, sore throat, mouth sores, or flu-like symptoms).[46163] [60360]

Data are limited regarding use of deferiprone during pregnancy; however, based on animal studies deferiprone may cause fetal harm when administered to a pregnant woman. In studies involving rats and rabbits, administration of deferiprone during organogenesis at doses 33% and 49%, respectively, of the maximum recommended human dose (MRHD) resulted in embryo-fetal death, skeletal and soft tissue malformations, and alterations to growth. Available human data include postmarketing reports from 39 pregnancies of deferiprone-treated females and 10 pregnancies of partners of deferiprone-treated males. Of the 39 pregnancies in drug-exposed females, 23 resulted in healthy newborns, 6 ended in spontaneous abortions, 9 had unknown outcomes, and 1 infant was born with anal atresia, nephroptosis, ventricular septal defect, hemivertebral, and urethral fistula. Of the 10 pregnancies of partners of drug-exposed males, 5 resulted in healthy newborns, 1 resulted in a healthy newborn with slight hypospadias, 1 was electively terminated, 1 resulted in intrauterine death of twins, and 2 had unknown outcomes. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Instruct drug recipients to immediately report a known or suspected pregnancy to their health care provider.

Advise patients that breast-feeding is not recommended during treatment with deferiprone, and for at least 2 weeks after the last dose, due to the potential for serious adverse reactions in the breastfed child, including the potential for tumorigenicity shown for deferiprone in animal studies. There is no information regarding the presence of deferiprone in human milk, the effects on the breastfed child, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Counsel patients about the reproductive risk and contraception requirements during deferiprone treatment. Deferiprone can cause fetal harm when administered to pregnant females; therefore, all females of childbearing potential should undergo pregnancy testing prior to initiating treatment. Advise female drug recipients to use effective contraception during treatment and for 6 months after cessation of therapy. The drug has also been associated with male-mediated teratogenicity; thus, contraception requirements are also recommended for deferiprone-treated males with female sexual partners of reproductive potential. Instruct males to use contraception during treatment and for 3 months after cessation of therapy.

ADVERSE REACTIONS

agranulocytosis / Delayed / 1.5-1.7
pancreatitis / Delayed / Incidence not known
enterocolitis / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
acute cerebellar syndrome / Early / Incidence not known
increased intracranial pressure / Early / Incidence not known
seizures / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
retinopathy / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
atrial fibrillation / Early / Incidence not known
pulmonary embolism / Delayed / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known

bone pain / Delayed / 25.0-25.0
neutropenia / Delayed / 6.0-8.0
elevated hepatic enzymes / Delayed / 8.0-8.0
glycosuria / Early / Incidence not known
depression / Delayed / Incidence not known
teeth grinding (bruxism) / Delayed / Incidence not known
thrombocytosis / Delayed / Incidence not known
ocular inflammation / Early / Incidence not known
hepatitis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hepatomegaly / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
zinc deficiency / Delayed / Incidence not known
trismus / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
metabolic acidosis / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
hypertension / Early / Incidence not known
hemoptysis / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
furunculosis / Delayed / Incidence not known

fever / Early / 28.0-28.0
abdominal pain / Early / 10.0-26.0
headache / Early / 2.0-20.0
vomiting / Early / 10.0-19.0
nausea / Early / 7.0-13.0
back pain / Delayed / 2.0-13.0
arthralgia / Delayed / 10.0-10.0
pharyngitis / Delayed / 9.0-9.0
cough / Delayed / 8.0-8.0
diarrhea / Early / 3.0-5.0
appetite stimulation / Delayed / 4.0-4.0
dyspepsia / Early / 2.0-2.0
weight gain / Delayed / 2.0-2.0
arthropathy / Delayed / 1.0-1.0
anorexia / Delayed / 1.0-1.0
urine discoloration / Early / Incidence not known
drowsiness / Early / Incidence not known
psychomotor impairment / Early / Incidence not known
infection / Delayed / Incidence not known
rash / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known
purpura / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
photosensitivity / Delayed / Incidence not known
diplopia / Early / Incidence not known
epistaxis / Delayed / Incidence not known
chills / Rapid / Incidence not known

DRUG INTERACTIONS

Aluminum Hydroxide: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) 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 deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) 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 deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) 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 deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) 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 deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) 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 deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
Betibeglogene Autotemcel: (Major) Avoid use of deferiprone for 6 months after betibeglogene autotemcel infusion due to risk of myelosuppression. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators (i.e., deferoxamine). Phlebotomy can be used instead of iron chelation, when appropriate.
Chlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) 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 deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
Clozapine: (Major) Avoid concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis, such as clozapine; however, if this is not possible, closely monitor the absolute neutrophil count and interrupt deferiprone therapy if neutropenia develops.
Deferasirox: (Major) Although the potential benefits of combination iron chelation therapy have been mentioned in the literature, deferasirox should not be combined with other iron chelator therapies (e.g., deferiprone) as the safety of such combinations has not been established.
Deferoxamine: (Major) Although the potential benefits of combination iron chelation therapy have been mentioned in the literature, deferiprone should not be combined with other iron chelator therapies (e.g., deferoxamine) as the safety of such combinations has not been established.
Dichlorphenamide: (Moderate) Use dichlorphenamide and deferiprone together with caution. Metabolic acidosis is associated with the use of dichlorphenamide and has been reported with the postmarketing use of deferiprone. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Major) Avoid the concomitant use of deferiprone and diclofenac. Deferiprone is a UDP glucuronosyltransferase (UGT) 1A6 substrate, and diclofenac inhibits UGT1A6. The in vitro glucuronidation of deferiprone was reduced by 78% in the presence of another UGT1A6 inhibitor. Side effects, such as nausea, increased liver enzymes, or risk for neutropenia may be increased.
Diclofenac; Misoprostol: (Major) Avoid the concomitant use of deferiprone and diclofenac. Deferiprone is a UDP glucuronosyltransferase (UGT) 1A6 substrate, and diclofenac inhibits UGT1A6. The in vitro glucuronidation of deferiprone was reduced by 78% in the presence of another UGT1A6 inhibitor. Side effects, such as nausea, increased liver enzymes, or risk for neutropenia may be increased.
Ethanol: (Major) Advise patients to avoid alcohol while taking deferiprone twice a day tablets. Consumption of alcohol while taking deferiprone twice a day tablets may result in more rapid release of deferiprone. At 40% (v/v) alcohol concentration in vitro dissolution studies, there was 88% release of deferiprone from a 1,000 mg deferiprone tablet (twice a day) within two hours compared to 4% release of deferiprone within 2 hours in the absence of alcohol.
Felbamate: (Major) Avoid concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis, such as felbamate; however, if this is not possible, closely monitor the absolute neutrophil count and interrupt deferiprone therapy if neutropenia develops.
Ferric carboxymaltose: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, ferric carboxymaltose, ferric citrate, sodium ferric gluconate complex, iron sucrose, sucroferric oxyhydroxide or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. Since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used together.
Ferric Derisomaltose: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, ferric carboxymaltose, ferric citrate, sodium ferric gluconate complex, iron sucrose, sucroferric oxyhydroxide or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. Since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used together.
Ferric Maltol: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used.
Ferumoxytol: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, ferric carboxymaltose, ferric citrate, sodium ferric gluconate complex, iron sucrose, sucroferric oxyhydroxide or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. Since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used together.
Iron - Injectable Only: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, ferric carboxymaltose, ferric citrate, sodium ferric gluconate complex, iron sucrose, sucroferric oxyhydroxide or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. Since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used together.
Iron Dextran: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, ferric carboxymaltose, ferric citrate, sodium ferric gluconate complex, iron sucrose, sucroferric oxyhydroxide or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. Since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used together.
Iron Salts: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used.
Iron Sucrose, Sucroferric Oxyhydroxide: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, ferric carboxymaltose, ferric citrate, sodium ferric gluconate complex, iron sucrose, sucroferric oxyhydroxide or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. Since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used together.
Iron: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used.
Methimazole: (Major) Avoid concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis, such as methimazole; however, if this is not possible, closely monitor the absolute neutrophil count and interrupt deferiprone therapy if neutropenia develops.
Milk Thistle, Silybum marianum: (Major) Avoid the concomitant use of deferiprone and Milk Thistle (Silymarin). Deferiprone is a UDP glucuronosyltransferase (UGT) 1A6 substrate, and milk thistle may inhibit UGT1A6. The in vitro glucuronidation of deferiprone was reduced by 78% in the presence of another UGT1A6 inhibitor. Side effects, such as nausea, increased liver enzymes, or risk for neutropenia may be increased.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used.
Polysaccharide-Iron Complex: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used.
Probenecid: (Major) Avoid the concomitant use of deferiprone and probenecid. Deferiprone is a UDP glucuronosyltransferase (UGT) 1A6 substrate, and probenecid inhibits this enzyme. The in vitro glucuronidation of deferiprone is reduced by 78% in the presence of phenylbutazone, another UGT1A6 inhibitor. Similar results may be seen when deferiprone and probenecid are administered concomitantly.
Probenecid; Colchicine: (Major) Avoid the concomitant use of deferiprone and probenecid. Deferiprone is a UDP glucuronosyltransferase (UGT) 1A6 substrate, and probenecid inhibits this enzyme. The in vitro glucuronidation of deferiprone is reduced by 78% in the presence of phenylbutazone, another UGT1A6 inhibitor. Similar results may be seen when deferiprone and probenecid are administered concomitantly.
Propylthiouracil, PTU: (Major) Avoid concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis, such as propylthiouracil, PTU; however, if this is not possible, closely monitor the absolute neutrophil count and interrupt deferiprone therapy if neutropenia develops.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used.
Zinc Salts: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) 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 deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
Zinc: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) 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 deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.

PREGNANCY AND LACTATION

Data are limited regarding use of deferiprone during pregnancy; however, based on animal studies deferiprone may cause fetal harm when administered to a pregnant woman. In studies involving rats and rabbits, administration of deferiprone during organogenesis at doses 33% and 49%, respectively, of the maximum recommended human dose (MRHD) resulted in embryo-fetal death, skeletal and soft tissue malformations, and alterations to growth. Available human data include postmarketing reports from 39 pregnancies of deferiprone-treated females and 10 pregnancies of partners of deferiprone-treated males. Of the 39 pregnancies in drug-exposed females, 23 resulted in healthy newborns, 6 ended in spontaneous abortions, 9 had unknown outcomes, and 1 infant was born with anal atresia, nephroptosis, ventricular septal defect, hemivertebral, and urethral fistula. Of the 10 pregnancies of partners of drug-exposed males, 5 resulted in healthy newborns, 1 resulted in a healthy newborn with slight hypospadias, 1 was electively terminated, 1 resulted in intrauterine death of twins, and 2 had unknown outcomes. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Instruct drug recipients to immediately report a known or suspected pregnancy to their health care provider.

Advise patients that breast-feeding is not recommended during treatment with deferiprone, and for at least 2 weeks after the last dose, due to the potential for serious adverse reactions in the breastfed child, including the potential for tumorigenicity shown for deferiprone in animal studies. There is no information regarding the presence of deferiprone in human milk, the effects on the breastfed child, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

MECHANISM OF ACTION

Deferiprone is an orally active chelating agent with an affinity for Fe3+. It binds with ferric ions to form neutral complexes (3:1 deferiprone to iron) that are stable in a wide range of pH values. Deferiprone has a high affinity for iron with a lower affinity for other trivalent metals such as copper, aluminum, and zinc.

PHARMACOKINETICS

Deferiprone is administered orally. Once in the systemic circulation, the apparent mean volume of distribution is 97 +/- 28 L. Deferiprone is primarily metabolized by UGT1A6. The major metabolite is 3-O-glucuronide, which lacks iron-binding capacity. The half-life of deferiprone is approximately 2 hours. The majority (more than 90%) of deferiprone is eliminated from the plasma within 5 to 6 hours, and 75% to 90% is recovered in the urine in the first 24 hours (primarily as the metabolite).[46163]
 
Affected cytochrome P450 isoenzymes and drug transporters: UDP-Glucuronosyltransferase (UGT1A6)
Deferiprone is primarily metabolized by UGT1A6. Inhibitors of UGT1A6 can reduce the metabolism of deferiprone by up to 78%.[46163]