Oral Azacitidine on the PBS

Azacitidine tablets are now available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of acute myeloid leukaemia (AML) following intensive induction chemotherapy.

The safety and efficacy of azacitidine tablets in this setting was evaluated in the pivotal QUAZAR AML-001 trial. In this double-blind study, patients with AML in first remission were randomised to receive oral azacitidine or placebo. Oral azacitidine was associated with a significantly longer overall survival compared to placebo (24.7 months versus 14.8 months). This favourable effect was noted in patients with both measurable residual disease (MRD)-positive and MRD-negative status at baseline.

The usual recommended dose is 300mg orally once daily for 14 days, followed by a 14-day treatment-free period. During the first two treatment cycles, an antiemetic is given 30 minutes before each azacitidine dose. In the event of disease relapse (5-15% blasts in the peripheral blood or bone marrow), treatment may be extended to 21 days of each 28-day cycle. However, treatment should be discontinued if disease progression occurs (blasts exceed 15% in either the peripheral blood or bone marrow).

The availability of an oral formulation improves convenience for patients and avoids injection site reactions which are common with the injectable formulation. Azacitidine tablets cannot be used interchangeably with azacitidine injection as there are significant differences in exposure and the dosing schedule. The mean oral bioavailability of azacitidine tablets relative to subcutaneous administration is around 11%. However, there is high interpatient variability. Food has a minimal effect on exposure and azacitidine tablets may be administered either with or without food.