ARANESP

What it is

ARANESP is darbepoetin alfa (rch) supplied as a sterile, clear, colourless, preservative-free aqueous solution for injection. ARANESP is a 165-amino acid protein containing 5 N-linked oligosaccharide chains, whereas erythropoietin contains only 3. The additional carbohydrate chains increase the molecular weight of the glycoprotein from approximately 30,000 to 37,000 daltons. Due to its increased sialic acid-containing carbohydrate content, ARANESP has an approximately 3-fold longer terminal half-life than erythropoietin and consequently a greater in vivo biologic activity when administered by either the subcutaneous or intravenous route.

Approved indications

— Treatment of anaemia associated with chronic renal failure (CRF). — Treatment of anaemia in patients with non-myeloid malignancies where anaemia develops as a result of concomitantly administered chemotherapy, and where blood transfusion is not considered appropriate.

Dosing overview

ARANESP should be used at the lowest dose that will gradually increase the haemoglobin concentration to approach a target of not more than 120 g/L; the rate of haemoglobin increase should not exceed 10 g/L in any 2-week period. For chronic renal failure, dosing varies by patient status and treatment phase. The initial or starting dose of ARANESP for patients on dialysis is 0.45 µg/kg body weight administered as a single subcutaneous or intravenous injection once weekly. Patients not on dialysis may receive any of the following initial doses: 0.45 µg/kg as a single subcutaneous injection once weekly, or 0.75 µg/kg as a single subcutaneous injection once every 2 weeks, or 1.5 µg/kg as a single subcutaneous injection once-monthly. For cancer patients, the recommended initial dose is 500 µg or 6.75 µg/kg body weight given once every 3 weeks as a single subcutaneous injection. Alternatively, once-weekly subcutaneous dosing can be given at 2.25 µg/kg body weight.

Key safety warnings

In some studies, use of erythropoiesis stimulating agents (ESAs) to treat anaemia in patients with cancer has been associated with increased mortality. ESAs should only be used to treat anaemia that has developed as a result of concomitantly administered chemotherapy, and only when blood transfusion is not considered appropriate. ESAs have been associated with an increased risk of death, serious cardiovascular events or stroke in controlled clinical trials when administered to target a haemoglobin of greater than 120 g/L. There was an increased risk of serious arterial and venous thromboembolic events, including myocardial infarction, stroke, congestive heart failure, and haemodialysis graft occlusion. A rate of haemoglobin rise of greater than 10 g/L over 2 weeks may also contribute to these risks. Patients with uncontrolled hypertension should not be treated with ARANESP; blood pressure should be controlled adequately before initiation of therapy. Blood pressure may rise during treatment of anaemia with ARANESP. Special care should be taken to closely monitor and control blood pressure in patients treated with ARANESP. Pure red cell aplasia (PRCA) in association with neutralising antibodies to native erythropoietin has been observed in patients treated with ESAs, including ARANESP. This has been reported predominantly in patients with CRF and in patients with hepatitis C treated with interferon and ribavirin. Most cases have been associated with subcutaneous administration of ESAs. Blistering and skin exfoliation reactions including Erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with ARANESP in the post-marketing environment.

Contraindications

ARANESP is contraindicated in patients with uncontrolled hypertension. ARANESP is contraindicated in patients with known sensitivity to products derived from mammalian cells. ARANESP is contraindicated in patients with known hypersensitivity to darbepoetin alfa or any of the excipients found in ARANESP.

PBS listing

ARANESP is listed on the PBS in multiple strengths and formulations with streamlined restriction status. Strengths listed include 10 µg, 20 µg, 30 µg, 40 µg, 50 µg, 60 µg, 80 µg, 100 µg and 150 µg in various presentations including pre-filled syringes and pre-filled injection pens. Ex-manufacturer prices range from A$52.82 to A$1230.09 depending on the strength and formulation.

Regulatory history

ARANESP darbepoetin alfa was first included in the Australian Register of Therapeutic Goods on 13 July 2001, with initial registrations for 10 µg, 30 µg, 50 µg, 60 µg and 80 µg strengths. Additional strengths (20 µg, 15 µg, 40 µg, 100 µg, 150 µg, 200 µg and 300 µg) were registered on 17 July 2001. The 500 µg strength was added on 26 November 2002. Pre-filled pen formulations became available from 7 June 2006, and pre-filled syringes with automatic needle guard were registered from 17 June 2010.