Agranulocytosis/Neutropenia

Fatal agranulocytosis can occur with deferiprone use. Deferiprone can also cause neutropenia, which may foreshadow agranulocytosis. Measure the absolute neutrophil count (ANC) before starting deferiprone therapy and monitor it regularly while on therapy [see Dosage and Administration (2.1)].

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 (ANC < 1.5 x 109/L).

Interrupt deferiprone if infection develops and monitor the ANC frequently.

Advise patients taking deferiprone 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 deferiprone-associated agranulocytosis is unknown. Agranulocytosis and neutropenia usually resolve upon discontinuation of deferiprone, 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 deferiprone treatment.

For agranulocytosis (ANC < 0.2 x 109/L) and severe neutropenia (0.2 x 109/L ≤ ANC < 0.5 x 109/L):

Consider hospitalization and other management as clinically appropriate.

Do not resume deferiprone in patients who have developed agranulocytosis unless potential benefits outweigh potential risks. Do not rechallenge patients who have developed neutropenia with deferiprone unless potential benefits outweigh potential risks.

For neutropenia (ANC < 1.5 x 109/L and ≥ 0.5 x 109/L):

Instruct the patient to immediately discontinue deferiprone and all other medications wit a potential to cause neutropenia.

Obtain a complete blood cell (CBC) count, including 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 109/L).