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 tablets and drugs or supplements containing polyvalent cations (e.g., iron, aluminum, or zinc). ( 2.2 , 7.2 )
7.1 Drugs Associated with Neutropenia or Agranulocytosis Avoid co-administration of deferiprone tablets with other drugs known to be associated with neutropenia or agranulocytosis. If co-administration is unavoidable, closely monitor the absolute neutrophil count <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span> .
7.2 Effect of Other Drugs on Deferiprone Tablets UDP-Glucuronosyltransferases (UGTs): Avoid use of UGT1A6 inhibitors (e.g., diclofenac, probenecid, or silymarin (milk thistle)) with deferiprone tablets <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 )]</span> .
Polyvalent
Cations: Deferiprone has the potential to bind polyvalent cations (e.g., iron, aluminum, and zinc); allow at least a 4-hour interval between deferiprone tablets and other medications (e.g., antacids), or supplements containing these polyvalent cations [see Dosage and Administration ( 2.2 )] .
Deferiprone tablets are 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 )
AND PRECAUTIONS Liver Enzyme Elevations: Monitor monthly and discontinue for persistent elevations. ( 5.2 )
Zinc
Deficiency: Monitor during therapy and supplement for deficiency. ( 5.3 ) Embryo-Fetal Toxicity: Can cause fetal harm. ( 5.4 )
5.1 Agranulocytosis and Neutropenia Fatal agranulocytosis can occur with FERRIPROX use. FERRIPROX can also cause neutropenia, which may foreshadow agranulocytosis. Measure the absolute neutrophil count (ANC) before starting FERRIPROX therapy and monitor it regularly while on therapy <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span> . 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 FERRIPROX therapy if neutropenia develops (ANC < 1.5 x 10 9 /L). Interrupt FERRIPROX if infection develops and monitor the ANC frequently. Advise patients taking FERRIPROX to immediately interrupt therapy and report to their physician if they experience any symptoms indicative of infection. The incidence of agranulocytosis was 1% of patients in pooled clinical trials of 642 patients with thalassemia syndromes and 0.5% of patients in pooled clinical trials of 196 patients with sickle cell disease or other anemias. The mechanism of FERRIPROX-associated agranulocytosis is unknown. Agranulocytosis and neutropenia usually resolve upon discontinuation of FERRIPROX, but there have been reports of agranulocytosis leading to death. Implement a plan to monitor for and to manage agranulocytosis and neutropenia prior to initiating FERRIPROX treatment. For agranulocytosis (ANC < 0.2 x 10 9 /L) and severe neutropenia (0.2 x 10 9 /L ≤ ANC < 0.5 x 10 9 /L): Consider hospitalization and other management as clinically appropriate. Do not resume FERRIPROX in patients who have developed agranulocytosis unless potential benefits outweigh potential risks. Do not rechallenge patients who have developed neutropenia with FERRIPROX unless potential benefits outweigh potential risks. For neutropenia (ANC < 1.5 x 10 9 /L and ≥ 0.5 x 10 9 /L): Instruct the patient to immediately discontinue FERRIPROX and all other medications with a potential to cause neutropenia. Obtain a complete blood cell (CBC) count, including a white blood cell (WBC) count corrected for the presence of nucleated red blood cells, an absolute neutrophil count (ANC), and a platelet count daily until recovery (ANC ≥ 1.5 x 10 9 /L). 5. 2 Liver Enzyme Elevations In pooled clinical trials, 7.5% of 642 patients with thalassemia syndromes treated with FERRIPROX developed increased ALT values. Four (0.62%) FERRIPROX-treated subjects discontinued the drug due to increased serum ALT levels and 1 (0.16%) due to an increase in both ALT and AST. In pooled clinical trials, 7.7% of 196 patients with sickle cell disease or other anemias treated with FERRIPROX developed increased ALT values. Monitor serum ALT values monthly during therapy with FERRIPROX and consider interruption of therapy if there is a persistent increase in the serum transaminase levels <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span> . 5. 3 Zinc Deficiency Decreased plasma zinc concentrations have been observed on FERRIPROX therapy. Monitor plasma zinc annually, and supplement in the event of a deficiency <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span> .
5.4 Embryo -F etal Toxicity Based on findings from animal reproduction studies and evidence of genotoxicity, FERRIPROX can cause fetal harm when administered to a pregnant woman. The available data on the use of FERRIPROX in pregnant women are insufficient to inform risk. In animal studies, administration of deferiprone during the period of organogenesis resulted in embryo-fetal death and malformations at doses lower than equivalent human clinical doses. Advise pregnant women and females of reproductive potential of the potential risk to the fetus <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 )]</span> . Advise females of reproductive potential to use an effective method of contraception during treatment with FERRIPROX and for at least six months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with FERRIPROX and for at least three months after the last dose [ see Use in Specific Populations ( 8.1 , 8.3 ) ] .