Ferriprox Special Precautions

Suggested management of cases of neutropenia is outlined as follows. It is recommended that such a management protocol be in place prior to initiating any patient on deferiprone treatment.
Treatment with deferiprone should not be initiated if the patient is neutropenic. The risk of agranulocytosis and neutropenia is higher, if the baseline absolute neutrophil count (ANC) is less than 1.5x10⁹/l.
In the event of neutropenia: Instruct the patient to immediately discontinue deferiprone and all other medicinal products with a potential to cause neutropenia. The patient should be advised to limit contact with other individuals in order to reduce the risk of infection. Obtain a complete blood cell (CBC) count, with a white blood cell (WBC) count, corrected for the presence of nucleated red blood cells, a neutrophil count, and a platelet count immediately upon diagnosing the event and then repeat daily. It is recommended that following recovery from neutropenia, weekly CBC, WBC, neutrophil and platelet counts continue to be obtained for three consecutive weeks, to ensure that the patient recovers fully. Should any evidence of infection develop concurrently with the neutropenia, the appropriate cultures and diagnostic procedures should be performed and an appropriate therapeutic regimen instituted.
In the event of severe neutropenia or agranulocytosis: Follow the guidelines previously mentioned and administer appropriate therapy such as granulocyte colony stimulating factor, beginning the same day that the event is identified; administer daily until the condition resolves. Provide protective isolation and if clinically indicated, admit patient to the hospital.
Limited information is available regarding rechallenge. Therefore, in the event of neutropenia, rechallenge is not recommended. In the event of agranulocytosis, a rechallenge is contraindicated.
Carcinogenicity/mutagenicity/effects on fertility: In view of the genotoxicity results, a carcinogenic potential of deferiprone cannot be excluded (see Pharmacology: Toxicology: Preclinical safety data under Actions). No animal studies to evaluate the potential effects of deferiprone on fertility have been reported.
Serum ferritin concentration/plasma Zn²⁺ concentration: It is recommended that serum ferritin concentrations, or other indicators of body iron load, be monitored every two to three months to assess the long-term effectiveness of the chelation regimen in controlling the body iron load. Interruption of therapy with deferiprone should be considered if serum ferritin measurements fall below 500 µg/l.
Monitoring of plasma Zn²⁺ concentration, and supplementation in case of a deficiency, is recommended.
HIV positive or other immune compromised patients: No data are available on the use of deferiprone in HIV positive or in other immune compromised patients. Given that deferiprone can be associated with neutropenia and agranulocytosis, therapy in immune compromised patients should not be initiated unless potential benefits outweigh potential risks.
Renal or hepatic impairment and liver fibrosis: There are no data available on the use of deferiprone in patients with renal or hepatic impairment. Since deferiprone is eliminated mainly via the kidneys, there may be an increased risk of complications in patients with impaired renal function. Similarly, as deferiprone is metabolised in the liver, caution must be exercised in patients with hepatic dysfunction. Renal and hepatic function should be monitored in this patient population during deferiprone therapy. If there is a persistent increase in serum alanine aminotransferase (ALT), interruption of deferiprone therapy should be considered.
In thalassaemia patients there is an association between liver fibrosis and iron overload and/or hepatitis C. Special care must be taken to ensure that iron chelation in patients with hepatitis C is optimal. In these patients careful monitoring of liver histology is recommended.
Cardiac function: Studies on cardiac iron concentrations suggest that deferiprone protects the heart against the toxicity of iron overload.
Discoloration of urine: Patients should be informed that their urine may show a reddish/brown discoloration due to the excretion of the iron-deferiprone complex.
Neurological disorders: Neurological disorders have been observed in children treated with approximately 2.5-times the maximum recommended dose for several months but have also been observed with standard doses of deferiprone. Prescribers are reminded that the use of doses above 100 mg/kg/day are not recommended. Deferiprone use should be discontinued if neurological disorders are observed (see Adverse Reactions and Overdosage).
Excipients: Ferriprox oral solution contains the colouring agent Sunset Yellow (E110) which may cause allergic reactions.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.