VIDAZA

What it is

Azacitidine-Teva is azacitidine powder for injection, supplied in vials containing 100 mg of azacitidine. The finished product is supplied in a sterile form for reconstitution as a suspension for subcutaneous injection or reconstitution as a solution with further dilution for intravenous infusion.

Approved indications

Azacitidine-Teva is indicated for the treatment of patients with: — Intermediate-2 and High-risk Myelodysplastic Syndromes (MDS) according to the International Prognostic Scoring System (IPSS). — Chronic Myelomonocytic Leukaemia (CMMoL (10%-29% marrow blasts without Myeloproliferative Disorder)). — Acute Myeloid Leukaemia (AML) with 20-30% blasts and multi-lineage dysplasia, according to World Health Organisation Classification (WHO), in whom allogeneic stem cell transplantation is not indicated.

Dosing overview

The recommended starting dose for the first treatment cycle, for all patients regardless of baseline haematology laboratory values, is 75 mg/m² of body surface area given subcutaneously or by intravenous infusion, daily for seven days, followed by a rest period of 21 days (28-day treatment cycle). Cycles should be repeated every 28 days. It is recommended that patients be treated for a minimum of six cycles. However, complete or partial response may require more than six treatment cycles. Treatment may be continued as long as the patient continues to benefit or until disease progression. Patients should be monitored for haematological response and renal toxicities, and a dose delay or reduction as described may be necessary. If unexplained reductions in serum bicarbonate levels to less than 20 mmol/L occur, the dose should be reduced by 50% on the next cycle. Similarly, if unexplained and clinically significant elevations of serum creatinine or blood urea nitrogen occur, the next cycle should be delayed until values return to normal or baseline and the dose should be reduced by 50% on the next treatment cycle.

Key safety warnings

Treatment with azacitidine is associated with anaemia, neutropenia and thrombocytopenia, particularly during the first 2 cycles. Thrombocytopenia may lead to bleeding and patients should be monitored for signs and symptoms of bleeding, particularly those with pre-existing or treatment-related thrombocytopenia. Patients with a history of severe congestive heart failure, clinically unstable cardiac disease or pulmonary disease were excluded from the pivotal clinical study and therefore the safety and efficacy of azacitidine in these patients has not been established. Cases of differentiation syndrome (also known as retinoic acid syndrome) have been reported in patients receiving injectable azacitidine. Differentiation syndrome may be fatal, and symptoms and clinical findings include respiratory distress, pulmonary infiltrates, fever, rash, pulmonary oedema, peripheral oedema, rapid weight gain, pleural effusions, pericardial effusions, hypotension and renal dysfunction. Treatment with high-dose IV corticosteroids and haemodynamic monitoring should be considered at first onset of symptoms or signs suggestive of differentiation syndrome. Renal abnormalities ranging from elevated serum creatinine to renal failure and death were reported rarely in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents. In addition, renal tubular acidosis, defined as a fall in serum bicarbonate to less than 20 mmol/L in association with an alkaline urine and hypokalaemia, developed in five subjects with chronic myelogenous leukaemia treated with azacitidine and etoposide. Patients with mild or moderate renal impairment should be monitored closely and the dose adjusted based on haematology and renal laboratory values.

Contraindications

Azacitidine-Teva is contraindicated in patients with known hypersensitivity to azacitidine or to any of the excipients, patients with advanced malignant hepatic tumours, pregnancy, and patients with severe renal impairment (creatinine clearance less than 30 mL/s/min).

Regulatory history

Azacitidine was first registered on the ARTG on 30 November 2009 under the brand VIDAZA (ARTG 153080). On 11 April 2013, the TGA approved an application to extend the route of administration for azacitidine (Vidaza) by adding IV infusion as an alternative to the approved subcutaneous route. This decision allows for the use of IV infusion for the treatment of Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and Acute Myeloid Leukemia.