FLUDARA

What it is

FLUDARA is fludarabine phosphate , a chemotherapy agent used to treat blood cancers. Fludarabine phosphate is a fluorinated nucleotide analogue of the antiviral agent vidarabine that is relatively resistant to deamination by adenosine deaminase.

Approved indications

— Treatment of B-cell chronic lymphocytic leukaemia.

Dosing overview

The recommended dose is 25 mg/m² body surface, given daily for five consecutive days every 28 days by the intravenous route. FLUDARA should be administered up to achievement of best response (complete or partial remission, usually six cycles) and then the drug should be discontinued. Dosage reduction is required in renally impaired patients.

Key safety warnings

**Neurotoxicity.** When used at high doses in dose ranging studies in patients with acute leukaemia, fludarabine phosphate was associated with severe neurological effects including blindness, coma and death. This severe central nervous system (CNS) toxicity occurred in 36% of patients treated intravenously with doses approximately four times greater (96 mg/m²/day for five to seven days) than the dose recommended for treatment of CLL. Administration of fludarabine phosphate can be associated with leukoencephalopathy (LE), acute toxic leukoencephalopathy (ATL) or reversible posterior leukoencephalopathy syndrome (RPLS). These may occur at the recommended dose, when fludarabine phosphate is given following, or in combination with, medications known to be associated with LE, ATL or RPLS, or when fludarabine phosphate is given to patients with other risk factors such as previous exposure to cranial or total body irradiation, Hematopoietic Cell Transplantation, Graft versus Host Disease, renal impairment, or hepatic encephalopathy. LE/ATL/RPLS may be irreversible, life threatening, or fatal. **Myelosuppression.** Severe bone marrow suppression, notably anaemia, thrombocytopenia and neutropenia, has been reported in patients treated with fludarabine phosphate. Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in adult patients. The duration of clinically significant cytopenia in the reported cases has ranged from approximately two months to one year. **Transfusion-associated graft versus host disease.** Transfusion associated graft versus host disease has been observed after transfusion of non-irradiated blood in fludarabine phosphate treated patients. Fatal outcome as a consequence of this disease has been reported with a high frequency. Therefore patients who require blood transfusion and who are undergoing, or who have received, treatment with fludarabine phosphate should receive irradiated blood only. **Autoimmune phenomena.** Life threatening and sometimes fatal autoimmune phenomena (e.g. autoimmune haemolytic anaemia, autoimmune thrombocytopenia, thrombocytopenic purpura, pemphigus, Evans' syndrome) have been reported to occur during or after treatment with fludarabine phosphate.

Contraindications

Fludarabine phosphate is contraindicated in those patients who are hypersensitive to this drug or its components, in renally impaired patients with creatinine clearance < 30 mL/min and in patients with haemolytic anaemia. Fludarabine phosphate is contraindicated during pregnancy and lactation.

PBS listing

The 10 mg tablet is listed on the PBS with unrestricted access and an ex-manufacturer price of A$831.94.

Regulatory history

FLUDARA was first approved on 1 May 2009. An oral formulation (10 mg tablet) was listed on the ARTG on 27 May 2002 under Sanofi-Aventis sponsorship.