FERRIPROX

What it is

Ferriprox is available as film-coated tablets containing 500 mg or 1000 mg of deferiprone, or as an oral solution containing 100 mg of deferiprone per millilitre.

Approved indications

— Treatment of iron overload in patients with thalassaemia major who are unable to take desferrioxamine or in whom desferrioxamine therapy has proven ineffective.

Dosing overview

Ferriprox is given as 25 mg/kg to 33 mg/kg body weight, orally, three times a day for a total daily dose of 75 mg/kg to 100 mg/kg body weight. The recommended initial total daily dose of Ferriprox is 75 mg/kg body weight. Doses above 100 mg/kg/day are not recommended because of the limited experience with these higher doses of Ferriprox. Dose adjustments should be tailored to the individual patient's response and therapeutic goals (maintenance or reduction of body iron burden). After starting Ferriprox therapy, 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 body iron load.

Key safety warnings

Ferriprox has been shown to cause neutropenia, including agranulocytosis, which may lead to the development of a serious and potentially life-threatening infection. It is recommended that a patient's neutrophil count be monitored every week. The most serious adverse event of therapy reported in clinical trials with Ferriprox is agranulocytosis (absolute neutrophil count < 0.5x10⁹/L) with an incidence of 1.9% (0.9 cases per 100 patient-years of treatment). Patients should be advised to report immediately to their physician any symptoms indicative of infection such as: fever, sore throat or flu-like symptoms. Neurological disorders have been observed in children treated with more than 2.5 times the maximum recommended dose for several months but have also been observed with standard doses of deferiprone in patients with mild or normal iron load. Prescribers are reminded that the dose should be adjusted to the severity of the iron load and that the use of doses above 100 mg/kg/day is not recommended. Ferriprox should be administered with caution to patients who may be at increased risk of prolongation of the cardiac QT interval (e.g., those with congestive heart failure, bradycardia, use of a diuretic, cardiac hypertrophy, hypokalemia or hypomagnesemia). Ferriprox has been associated with hepatotoxicity (increased ALT) in some patients. If there is a persistent increase in serum ALT, interruption of Ferriprox therapy should be considered.

Contraindications

Ferriprox is contraindicated in patients who have demonstrated hypersensitivity to the active substance or any of the excipients, have a history of recurrent episodes of neutropenia, have a history of agranulocytosis, or are pregnant or breast-feeding.

PBS listing

Ferriprox is listed on the PBS in tablet form (500 mg and 1000 mg strengths) and as an oral solution (100 mg per mL in 250 mL bottles). All formulations are listed with streamlined restriction. The ex-manufacturer price is A$192.62 for the oral solution and A$385.23 for both tablet strengths.

Regulatory history

Ferriprox 500 mg tablets were first registered on the ARTG on 9 April 2003. The oral solutions (25 g/250 mL and 50 g/500 mL bottles) were registered on 26 March 2008, and the 1000 mg tablets were registered on 6 July 2017. An AusPAR was published in August 2011 for the approval of an increase in dosage for Ferriprox from 75 mg/kg/day to a starting dose of 75 mg/kg/day which can be increased to 100 mg/kg/day. In November 2017, the PBAC recommended the listing of the 1000 mg tablet strength on the PBS under the Highly Specialised Drugs section with streamlined authority required restriction for transfusional iron overload associated with thalassaemia major.