Deferiprone

Pronunciation: de-FER-i-prone
Class: Chelating agent

Trade Names

Ferriprox
- Tablets, oral 500 mg

Pharmacology

Orally active chelating agent that has a high affinity for binding with iron.

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Pharmacokinetics

Absorption

Rapidly absorbed. T _max is approximately 1 to 2 h. Mean C _max is 20 mcg/mL, and mean AUC is 53 mcg•h/mL. Administration with food decreases C _max by 38% and AUC by 10%.

Distribution

Protein binding is less than 10%. Vd is approximately 1 to 1.6 L/kg.

Metabolism

Majority of deferiprone is metabolized by UGT1A6. Major metabolite is the 3-O-glucuronide, which lacks iron binding capability.

Elimination

More than 90% is eliminated from plasma 5 to 6 h after administration; 75% to 90% is excreted in the urine as the metabolite. Elimination half-life is 1.9 h.

Special Populations

Renal Function Impairment

Not evaluated.

Hepatic Function Impairment

Not conclusively evaluated.

Elderly

Pharmacokinetics have not been studied in elderly patients.

Children

Pharmacokinetics have not been studied in pediatric patients.

Gender

Influence of gender has not been established.

Race

Influence of race has not been established.

Weight

Influence of obesity has not been established.

Indications and Usage

Treatment of transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate.

Contraindications

Hypersensitivity to deferiprone or to any of the components of the product.

Dosage and Administration

Adults

PO Initial dosage is 25 mg/kg 3 times daily. Adjust dose based on patient response and therapeutic goals (maintenance or reduction of body iron burden) up to a max dosage of 33 mg/kg 3 times daily.

General Advice

• Administer 3 times daily; may take with meals to reduce nausea.
• Round the dose to the nearest 250 mg (half-tablet).
• If the serum ferritin consistently falls below 500 mcg/L, consider temporary interruption of therapy.
• Allow at least a 4 h interval between administration of deferiprone and other medications or supplements containing polyvalent cations (eg, aluminum, iron, zinc).

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Drugs associated with neutropenia or agranulocytosis

Avoid concomitant use. However, if this is not possible, closely monitor the absolute neutrophil count (ANC).

Polyvalent cations (eg, aluminum, cation-containing antacids, iron, zinc)

Deferiprone has the potential to bind polyvalent cations (eg, iron). Allow at least a 4-hour interval between deferiprone and other medications (eg, antacids) or supplements containing these polyvalent cations.

UGT1A6 inhibitors (eg, silymarin [milk thistle])

Coadministration has not been evaluated. Closely monitor for adverse reactions that may require downward dose titration or interruption.

Adverse Reactions

Cardiovascular

Atrial fibrillation, cardiac failure, hypertension, hypotension (postmarketing).

CNS

Headache (3%); bruxism, cerebellar syndrome, cerebral hemorrhage, convulsion, depression, enteroviral encephalitis, gait disturbance, intracranial pressure increased, obsessive-compulsive disorder, psychomotor skills impaired, pyramidal tract syndrome, somnolence (postmarketing).

Dermatologic

Cryptococcal cutaneous infection, furuncle, Henoch-Schönlein purpura, hyperhidrosis, photosensitivity reaction, pruritus, pustular rash, rash, subcutaneous abscess, urticaria (postmarketing).

EENT

Diplopia, papilledema, periorbital edema, pharyngitis, retinal toxicity (postmarketing).

GI

Nausea (13%); abdominal pain or discomfort, vomiting (10%); diarrhea (3%); dyspepsia (2%); enterocolitis, gastric ulcer, pancreatitis, parotid gland enlargement, rectal hemorrhage (postmarketing).

Genitourinary

Chromaturia (15%); glycosuria, hemoglobinuria (postmarketing).

Hematologic-Lymphatic

Neutropenia (6%); agranulocytosis (2%); pancytopenia, thrombocytosis (postmarketing).

Hepatic

Hepatomegaly, infectious hepatitis, jaundice (postmarketing).

Hypersensitivity

Anaphylactic shock, hypersensitivity (postmarketing).

Lab Tests

Increased ALT (8%); decreased neutrophils (7%); increased AST (1%); increased blood bilirubin, increased blood CPK (postmarketing).

Metabolic-Nutritional

Increased appetite (4%); increased weight (2%); decreased appetite (1%); dehydration, metabolic acidosis, peripheral edema (postmarketing).

Musculoskeletal

Arthralgia (10%); back pain, pain in extremity (2%); arthropathy (1%); chondropathy, myositis, trismus (postmarketing).

Respiratory

Acute respiratory distress syndrome, epistaxis, hemoptysis, pneumonia, pulmonary embolism (postmarketing).

Miscellaneous

Chills, hypospadias, multiorgan failure, pyrexia, sepsis (postmarketing).

Precautions

Warnings Agranulocytosis/Neutropenia Deferiprone can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. Interrupt therapy if neutropenia or infection develops, and monitor the ANC more frequently. Advise patients to immediately report any symptoms indicative of infection.

Monitor Measure serum ferritin concentration every 2 to 3 mo. Measure ANC before starting therapy and weekly during therapy. For ANC less than 1.5 × 10 9 /L and more than 0.5 × 10 9 /L, discontinue therapy and all other medications with a potential to cause neutropenia, and obtain a CBC, including a WBC corrected for the presence of nucleated RBCs, ANC, and platelet count daily until ANC returns to at least 1.5 × 10 9 /L. Monitor serum ALT monthly. Monitor plasma zinc.

Pregnancy

Category D . Can cause fetal harm.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution, usually starting at the low end of the dosage range because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Hypersensitivity

Henoch-Schönlein purpura, periorbital edema with skin rash, and urticaria have been reported.

Laboratory Test Abnormalities

Elevations in ALT and AST and decreases in zinc concentrations may occur. Consider interruption of therapy if increased serum transaminase levels persist.

QT prolongation

A thorough QT study has not been conducted, but 1 patient with a history of QT prolongation experienced torsades de pointes during therapy. Use with caution in patients at increased risk of QT prolongation.

Overdosage

Symptoms

With long-term overdose, axial hypotonia, cerebellar symptoms, diplopia, hand movements, lateral nystagmus, and psychomotor slowdown may occur.

Patient Information

• Advise patient to read the Medication Guide prior to first use and to reread it with each refill.
• Inform patients of the risks of developing agranulocytosis and instruct them to immediately interrupt therapy and report to their health care provider if they experience symptoms of infection (eg, fever, flu-like symptoms, sore throat).
• Advise patients that the amount of deferiprone prescribed is based on body weight and on the therapeutic goal (reduction or stabilization of body iron load).
• Advise patients to take the first dose in the morning, the second dose at midday, and the third dose in the evening. Inform patients that taking deferiprone with meals may reduce nausea.
• Instruct patients that if a dose is missed, they should take it as soon as possible. If it is almost time for the next dose, advise the patient to skip the missed dose and resume their regular dosing schedule. Inform patients not to double doses.
• Inform patients that their urine may show a reddish/brown discoloration. Advise patients that this is a very common sign of the desired effect and is not harmful.
• Counsel women of reproductive potential to avoid pregnancy while taking deferiprone and to immediately notify their health care provider if they become pregnant or plan to become pregnant.
• Inform patients that they should not breast-feed during therapy.
• Inform patients to immediately seek medical attention if they experience dizziness, light-headedness, palpitations, seizures, or syncope.

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