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Aranesp SureClick
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Drug Class Description
Pharmacotherapeutic group: Anti-anemic preparations, other Antianemic preparations. ATC Code: B03XA02.Human erythropoietin is an endogenous glycoprotein hormone that is the primary regulator of erythropoiesis through specific interaction with the erythropoietin receptor on the erythroid progenitor cells in the bone marrow. The production of erythropoietin primarily occurs in and is regulated by the kidney in response to changes in tissue oxygenation. Production of endogenous erythropoietin is impaired in patients with chronic renal failure and the primary cause of their anaemia is due to erythropoietin deficiency. In patients with cancer receiving chemotherapy the etiology of anaemia is multifactorial. In these patients, erythropoietin deficiency and a reduced response of erythroid progenitor cells to endogenous erythropoietin both contribute significantly towards their anaemia.Darbepoetin alfa stimulates erythropoiesis by the same mechanism as the endogenous hormone. Darbepoetin alfa has five N-linked carbohydrate chains whereas the endogenous hormone and recombinant human erythropoietins (r-HuEPO) have three. The additional sugar residues are molecularly indistinct from those on the endogenous hormone. Due to its increased carbohydrate content darbepoetin alfa has a longer terminal half-life than r-HuEPO and consequently a greater in vivo activity. Despite these molecular changes, darbepoetin alfa retains a very narrow specificity for the erythropoietin receptor.Chronic renal failure patientsPatients with CRF experienced greater risks for death and serious cardiovascular events when administered ESAs to target higher versus lower haemoglobin levels (13.5 g/dl (8.4 mmol/l) versus 11.3 g/dl (7.1 mmol/l); 14 g/dl (8.7 mmol/l) versus 10 g/dl (6.2 mmol/l) in two clinical studies.In a randomised, double-blind, placebo-controlled study (TREAT) of 4,038 CRF patients not on dialysis with type 2 diabetes and haemoglobin levels 11 g/dl, patients received either treatment with darbepoetin alfa to target haemoglobin levels of 13 g/dl or placebo (with darbepoetin alfa rescue at haemoglobin less than 9 g/dl). The study did not meet either primary objective of demonstrating a reduction in risk for all-cause mortality, or cardiovascular morbidity (darbepoetin alfa vs placebo; HR 1.05, 95% CI (0.94, 1.17)), or all-cause mortality or end stage renal disease (ESRD) (darbepoetin alfa vs placebo; HR 1.06, 95% CI (0.95, 1.19)).Analysis of the individual components of the composite endpoints showed the following HR (95% CI): death 1.05 (0.92, 1.21), congestive heart failure (CHF) 0.89 (0.74, 1.08), myocardial infarction (MI) 0.96 (0.75, 1.23), stroke 1.92 (1.38, 2.68), hospitalisation for myocardial ischaemia 0.84 (0.55, 1.27), ESRD 1.02 (0.87, 1.18).Cancer patients receiving chemotherapyIn a prospective, randomised double-blind, placebo-controlled study conducted in 314 lung cancer patients receiving platinum containing chemotherapy there was a significant reduction in transfusion requirements (p < 0.001).Clinical studies have demonstrated that darbepoetin alfa had similar effectiveness when administered as a single injection either once every three weeks, once every two weeks, or weekly without any increase in total dose requirements.The safety and effectiveness of once every three weeks dosing of Aranesp therapy in reducing the requirement for red blood cell transfusions in patients undergoing chemotherapy was assessed in a randomised, double-blind, multinational study. This study was conducted in 705 anaemic patients with non-myeloid malignancies receiving multi-cycle chemotherapy. Patients were randomised to receive Aranesp at 500 ?g once every three weeks or 2.25 ?g /kg once weekly. In both groups, the dose was reduced by 40% of the previous dose (e.g., for first dose reduction, to 300 ?g in the once every three weeks group and 1.35 ?g/kg in the once weekly group) if haemoglobin increased by more than 1 g/dl in a 14-day period. In the once every three weeks group, 72% of patients required dose reductions. In the once weekly group, 75% of patients required dose reductions. This study supports 500 ?g once every three weeks being comparable to once weekly administration with respect to the incidence of subjects receiving at least one red blood cell transfusion from week 5 to the end of treatment phase.In a prospective, randomised double-blind, placebo-controlled study conducted in 344 anaemic patients with lymphoproliferative malignancies receiving chemotherapy there was a significant reduction in transfusion requirements and an improvement in haemoglobin response (p < 0.001). Improvement in fatigue, as measured by the Functional Assessment of Cancer Therapy-fatigue (FACT-fatigue) scale, was also observed.Erythropoietin is a growth factor that primarily stimulates red blood cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumour cells.Survival and tumour progression have been examined in five large controlled studies involving a total of 2833 patients, of which four were double-blind placebo-controlled studies and one was an open-label study. Two of the studies recruited patients who were being treated with chemotherapy. The target haemoglobin concentration in two studies was > 13 g/dl; in the remaining three studies it was 12-14 g/dl. In the open-label study there was no difference in overall survival between patients treated with recombinant human erythropoietin and controls. In the four placebo-controlled studies the hazard ratios for overall survival ranged between 1.25 and 2.47 in favour of controls. These studies have shown a consistent unexplained statistically significant excess mortality in patients who have anaemia associated with various common cancers who received recombinant human erythropoietin compared to controls. Overall survival outcome in the trials could not be satisfactorily explained by differences in the incidence of thrombosis and related complications between those given recombinant human erythropoietin and those in the control group.A systematic review has also been performed involving more than 9000 cancer patients participating in 57 clinical trials. Meta-analysis of overall survival data produced a hazard ratio point estimate of 1.08 in favour of controls (95% CI: 0.99, 1.18; 42 trials and 8167 patients).An increased relative risk of thromboembolic events (RR 1.67, 95% CI: 1.35, 2.06, 35 trials and 6769 patients) was observed in patients treated with recombinant human erythropoietin. There is therefore consistent evidence to suggest that there may be significant harm to patients with cancer who are treated with recombinant human erythropoietin. The extent to which these outcomes might apply to the administration of recombinant human erythropoietin to patients with cancer, treated with chemotherapy to achieve haemoglobin concentrations less than 13 g/dl, is unclear because few patients with these characteristics were included in the data reviewed.A patient-level data analysis has also been performed on more than 13,900 cancer patients (chemo-, radio-, chemoradio-, or no therapy) participating in 53 controlled clinical trials involving several epoetins. Meta-analysis of overall survival data produced a hazard ratio point estimate of 1.06 in favour of controls (95% CI: 1.00, 1.12; 53 trials and 13933 patients) and for the cancer patients receiving chemotherapy, the overall survival hazard ratio was 1.04 (95% CI: 0.97, 1.11; 38 trials and 10,441 patients). Meta-analyses also indicate consistently a significantly increased relative risk of thromboembolic events in cancer patients receiving recombinant human erythropoietin
Generic Name
Darbepoetin alfa
Drug Description
Each pre-filled pen contains 10 micrograms of darbepoetin alfa in 0.4 ml (25 µg/ml).Each pre-filled pen contains 15 micrograms of darbepoetin alfa in 0.375 ml (40 µg/ml).Each pre-filled pen contains 20 micrograms of darbepoetin alfa in 0.5 ml (40 µg/ml).Each pre-filled pen contains 30 micrograms of darbepoetin alfa in 0.3 ml (100 µg/ml).Each pre-filled pen contains 40 micrograms of darbepoetin alfa in 0.4 ml (100 µg/ml).Each pre-filled pen contains 50 micrograms of darbepoetin alfa in 0.5 ml (100 µg/ml).Each pre-filled pen contains 60 micrograms of darbepoetin alfa in 0.3 ml (200 µg/ml).Each pre-filled pen contains 80 micrograms of darbepoetin alfa in 0.4 ml (200 µg/ml).Each pre-filled pen contains 100 micrograms of darbepoetin alfa in 0.5 ml (200 µg/ml).Each pre-filled pen contains 130 micrograms of darbepoetin alfa in 0.65 ml (200 µg/ml).Each pre-filled pen contains 150 micrograms of darbepoetin alfa in 0.3 ml (500 µg/ml).Each pre-filled pen contains 300 micrograms of darbepoetin alfa in 0.6 ml (500 µg/ml).Each pre-filled pen contains 500 micrograms of darbepoetin alfa in 1.0 ml (500 µg/ml).Darbepoetin alfa is produced by gene-technology in Chinese Hamster Ovary Cells (CHO-K1).Excipients:Each pre-filled pen contains 1.52 mg of sodium in 0.4 ml.Each pre-filled pen contains 1.42 mg of sodium in 0.375 ml.Each pre-filled pen contains 1.90 mg of sodium in 0.5 ml.Each pre-filled pen contains 1.14 mg of sodium in 0.3 ml.Each pre-filled pen contains 1.52 mg of sodium in 0.4 ml.Each pre-filled pen contains 1.90 mg of sodium in 0.5 ml.Each pre-filled pen contains 1.14 mg of sodium in 0.3 ml.Each pre-filled pen contains 1.52 mg of sodium in 0.4 ml.Each pre-filled pen contains 1.90 mg of sodium in 0.5 ml.Each pre-filled pen contains 2.46 mg of sodium in 0.65 ml.Each pre-filled pen contains 1.14 mg of sodium in 0.3 ml.Each pre-filled pen contains 2.27 mg of sodium in 0.6 ml.Each pre-filled pen contains 3.79 mg of sodium in 1 ml.
Presentation
Solution for injection (injection) in a pre-filled pen (SureClickTM).Clear, colourless solution
Indications
Treatment of symptomatic anaemia associated with chronic renal failure (CRF) in adults and paediatric patients.
Treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.
Adult Dosage
Aranesp treatment should be initiated by physicians experienced in the above mentioned indications.
Posology
Treatment of symptomatic anaemia in adult and paediatric chronic renal failure patients
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