3 The technologies

3.1 Epoetin and darbepoetin are erythropoiesis‑stimulating agents.

Epoetins

3.2 Epoetin alfa, beta, theta and zeta are recombinant human erythropoietin analogues used to shorten the period of symptomatic anaemia in people having cytotoxic chemotherapy. Epoetins are recommended for use when haemoglobin concentrations are 100 g/litre or lower, and target values up to 120 g/litre.

Epoetin alfa

3.3 There are 2 brands of epoetin alfa (Eprex, Janssen‑Cilag and Binocrit, Sandoz), and both have UK marketing authorisations for the 'treatment of anaemia and reduction of transfusion requirements in adult patients receiving chemotherapy for solid tumours, malignant lymphoma or multiple myeloma, who are at risk of transfusion as assessed by the patient's general status (for example, cardiovascular status, pre‑existing anaemia at the start of chemotherapy)'. Binocrit is a biosimilar medicine referenced to Eprex (see section 3.18).

3.4 The summary of product characteristics for Eprex and Binocrit lists headache, nausea and pyrexia as very common adverse reactions, and deep vein thrombosis, hypertension, pulmonary embolism, diarrhoea, vomiting, rash, arthralgia and flu‑like illness as common adverse reactions in patients with cancer. The summary of product characteristics for Binocrit also lists stroke as a common adverse reaction. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.5 Eprex and Binocrit are available in pre‑filled syringes at net prices of £5.53 and £4.33 per 1000 units respectively (excluding VAT; British national formulary [BNF], March 2014). They are administered by subcutaneous injection at a recommended initial dose of 150 units/kg body weight 3 times weekly or 450 units/kg body weight once a week. Costs may vary in different settings because of negotiated procurement discounts.

Epoetin beta

3.6 Epoetin beta (NeoRecormon, Roche Products) has a UK marketing authorisation for the 'treatment of symptomatic anaemia in adult patients with non‑myeloid malignancies who are receiving chemotherapy'.

3.7 The summary of product characteristics lists the following common adverse reactions for epoetin beta in patients with cancer: hypertension, thromboembolic event and headache. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.8 Epoetin beta is available in a pre‑filled syringe at a net price of £3.51 per 500 units (excluding VAT; BNF, March 2014). It is administered by subcutaneous injection at a recommended initial dose of 450 units/kg body weight once a week or in divided doses 3 to 7 times a week. Costs may vary in different settings because of negotiated procurement discounts.

Epoetin theta

3.9 Epoetin theta (Eporatio, Teva UK) has a UK marketing authorisation for the 'treatment of symptomatic anaemia in adult patients with non‑myeloid malignancies who are receiving chemotherapy'.

3.10 The summary of product characteristics lists the following common adverse reactions for epoetin theta in patients with cancer: headache, hypertension, skin reactions, arthralgia and flu‑like illness. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.11 Epoetin theta is available in a pre‑filled syringe at a net price of £5.99 per 1000 units (excluding VAT; BNF, March 2014). It is administered by subcutaneous injection at a recommended initial dose of 20,000 units once a week. Costs may vary in different settings because of negotiated procurement discounts.

Epoetin zeta

3.12 Epoetin zeta (Retacrit, Hospira UK) is a biosimilar medicine referenced to Eprex (see section 3.18). It has a UK marketing authorisation for the 'treatment of anaemia and reduction of transfusion requirements in adult patients receiving chemotherapy for solid tumours, malignant lymphoma or multiple myeloma, who are at risk of transfusion as assessed by the patient's general status (for example, cardiovascular status, pre‑existing anaemia at the start of chemotherapy)'.

3.13 The summary of product characteristics for epoetin zeta lists headache as a very common adverse reaction, and stroke, dizziness, deep vein thrombosis, an increase in blood pressure, pulmonary embolism, non‑specific skin rashes, joint pains, flu‑like symptoms, feeling of weakness and tiredness as common adverse reactions in patients with cancer. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.14 Epoetin zeta is available in a pre‑filled syringe at a net price of £5.66 per 1000 units (excluding VAT; BNF, March 2014). It is administered by subcutaneous injection at a recommended initial dose of 150 units/kg body weight 3 times weekly or 450 units/kg body weight once a week. Costs may vary in different settings because of negotiated procurement discounts.

Darbepoetin alfa

3.15 Darbepoetin alfa (Aranesp, Amgen) is a hyperglycosylated derivative of epoetin that stimulates erythropoiesis by the same mechanism as the endogenous hormone. Aranesp has a UK marketing authorisation for the 'treatment of symptomatic anaemia in adult cancer patients with non‑myeloid malignancies who are receiving chemotherapy'. The summary of product characteristics recommends that darbepoetin alfa should be used at haemoglobin concentrations of 100 g/litre or lower, with target values up to 120 g/litre.

3.16 The summary of product characteristics for darbepoetin alfa lists hypersensitivity and oedema as very common adverse reactions, and hypertension, thromboembolic events (including pulmonary embolism), rash, erythema and injection‑site pain as common adverse reactions in patients with cancer. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.17 Darbepoetin alfa is available in a pre‑filled syringe at a net price of £14.68 per 10 micrograms (excluding VAT; BNF, March 2014). It is administered by subcutaneous injection at a recommended initial dose of 500 micrograms (6.75 micrograms/kg body weight) once every 3 weeks or 2.25 micrograms/kg body weight once a week. Costs may vary in different settings because of negotiated procurement discounts.

Biosimilars

3.18 This appraisal includes 2 biosimilar medicines, Binocrit and Retacrit, both of which are referenced to Eprex. The British national formulary (May 2014) states: 'A biosimilar medicine is a new biological product that is similar to a medicine that has already been authorised to be marketed (the biological reference medicine) in the European Union. The active substance of a biosimilar medicine is similar, but not identical, to the biological reference medicine. Biological products are different from standard chemical products in terms of their complexity and although theoretically there should be no important differences between the biosimilar and the biological reference medicine in terms of safety or efficacy, when prescribing biological products, it is good practice to use the brand name. This will ensure that substitution of a biosimilar medicine does not occur when the medicine is dispensed'.