Overview
11 DESCRIPTION Deferiprone Tablets 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 C 7 H 9 NO 2 and its molecular weight is 139.15 g/mol. Deferiprone has the following structural formula: Deferiprone is a white to pinkish-white powder.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Deferiprone is a chelating agent with an affinity for ferric ions (iron III). Deferiprone binds with ferric ions to form neutral 3:1 (deferiprone:iron) complexes that are stable at physiological pH. 12.2 Pharmacodynamics No clinical studies were performed to assess the relationship between the dose of deferiprone and the amount of iron eliminated from the body. Cardiac Electrophysiology At the maximum approved recommended dose, deferiprone does not prolong the QT interval to any clinically relevant extent. 12.3 Pharmacokinetics Deferiprone Tablets (three times a day), 1,000 mg and 500 mg The mean C max and AUC of deferiprone was 20 mcg/mL and 50 mcg∙h/mL, respectively, in healthy subjects.
Indications
- 1 INDICATIONS AND USAGE Deferiprone tablets are indicated for the treatment of transfusional iron overload in adult patients with thalassemia syndromes when current chelation therapy is inadequate. Deferiprone tablets are an iron chelator indicated for the treatment of transfusional iron overload in adult patients with thalassemia syndromes when current chelation therapy is inadequate. ( 1 ) 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.
Common Doses
- 000 mg
- 500 mg
- 75 mg
- 99 mg
Dosage
2 DOSAGE AND ADMINISTRATION Deferiprone tablets are available in two formulations. A 1,000 mg formulation and a 500 mg formulation, which have different dosing regimens to achieve the same total daily dosage. ( 2.1 ) 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. ( 2.1 , 3 ) Deferiprone tablets (three times a day), 1,000 mg: Starting oral dosage: 75 mg/kg/day (actual body weight) in three divided doses ( 2.
Black Box Warning
WARNING: AGRANULOCYTOSIS AND NEUTROPENIA Deferiprone can cause agranulocytosis that can lead to serious infections and death. Neutropenia may precede the development of agranulocytosis. [see Warnings and Precautions (5.1) ] Measure the absolute neutrophil count (ANC) before starting deferiprone therapy and monitor regularly while on therapy. Interrupt deferiprone therapy if neutropenia develops. [see Warnings and Precautions (5.1) ] Interrupt deferiprone if infection develops, and monitor the ANC more frequently. [see Warnings and Precautions (5.
Contraindications
- 4 CONTRAINDICATIONS Deferiprone is contraindicated in patients with known hypersensitivity to deferiprone or to any of the excipients in the formulations. The following reactions have been reported in association with the administration of deferiprone: Henoch-Schönlein purpura; urticaria; and periorbital edema with skin rash [see Adverse Reactions (6.2) ]. Hypersensitivity to deferiprone or to any of the excipients in the formulations. ( 4 )
Side Effects
- 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) ] The most common adverse reactions in patients with thalassemia (incidence > 6%) are nausea, vomiting, abdominal pain, arthralgia, ALT increased and neutropenia. (5.1, 6) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc.
Interactions
- 7 DRUG INTERACTIONS Drugs Associated with Neutropenia or Agranulocytosis: Avoid co-administration. If co-administration is unavoidable, closely monitor the absolute neutrophil count. ( 7.1 ) UGT1A6 Inhibitors: Avoid co-administration. ( 7.2 ) Polyvalent Cations: Allow at least a 4-hour interval between administration of deferiprone and drugs or supplements containing polyvalent cations (e.g., iron, aluminum, or zinc). ( 2.6 , 7.2 ) 7.