Darbepoetin Alfa is an active pharmaceutical ingredient in the Other Antianemic Preparations group (B03XA). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised March 13, 2026[1]
2). Treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.
How to take
GB
CACanada· Health Canada
19 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
Treatment of Anemia in Chronic Kidney Disease • ARANESP® (darbepoetin alfa injection) is indicated for the treatment of anemia associated with chronic kidney disease (CKD), including patients on dialysis and patients not on dialysis.
o Aranesp is not intended for patients who require immediate correction of severe anemia or emergency transfusions. o Aranesp is not indicated for other causes of anemia such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding which should be managed appropriately.
Treatment of Anemia due to Chemotherapy in Patients with Non-Myeloid Malignancies • Aranesp is indicated for the treatment of anemia due to the effect of concomitantly administered myelosuppressive chemotherapy in adult patients with advanced or metastatic, non-myeloid malignancies.
o In patients with a long life expectancy, the decision to administer erythropoiesis- stimulating agents (ESAs) should be based on a benefit-risk assessment with the participation of the individual patient. This should take into account the specific clinical context such as (but not limited to) the type of tumour and its stage, the degree of anemia, life expectancy, the environment in which the patient is being treated and known risks of transfusions and ESAs.
USUnited States· FDA
1 product
Uses
USOfficial regulatory label· revised March 8, 2026[3]
1 ). 2 ). 3 ). 3 ). 3 ). 3 ). 3 ). 1 Anemia Due to Chronic Kidney Disease Aranesp is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and patients not on dialysis. 2 Anemia Due to Chemotherapy in Patients with Cancer Aranesp is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.
3 Limitations of Use Aranesp has not been shown to improve quality of life, fatigue, or patient well-being. Aranesp is not indicated for use: • In patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy.
• In patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure. • In patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion. • As a substitute for RBC transfusions in patients who require immediate correction of anemia.
EUEuropean Union· EMA
1 product
Uses
EUOfficial regulatory label· revised January 13, 2026[4]
2). Treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.
How to take
EU
Drug interactions
Known interactions involving Darbepoetin Alfa. Select one for details. This list is informational and not a complete interaction checker.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PLGB138320016 · revised March 13, 2026
[2]Health Canada (DPD) · 02246353 · revised March 22, 2025
[3]FDA DailyMed · 0fd36cb9-c4f6-41… · revised March 8, 2026 [PDF]
[4]European Medicines Agency · EMEA/H/C/000332 · revised January 13, 2026
[5]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
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 Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary.
5 mmol/L). Subcutaneous use is preferable in patients who are not receiving haemodialysis to avoid the puncture of peripheral veins. 5 mmol/L). Caution should be exercised with escalation of Aranesp doses in patients with chronic renal failure.
1). Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. 5 mmol/L). 5 mmol/L) are observed are described below. 25 mmol/L) over a four week period should be avoided.
If it occurs, appropriate dose adjustment should be made as provided. Treatment with Aranesp is divided into two stages, correction and maintenance phase. Guidance is given separately for adult and paediatric patients. 45 mcg/kg body weight, as a single injection once weekly.
5 mcg/kg once monthly. 6 mmol/L) in four weeks) increase the dose by approximately 25%. Dose increases must not be made more frequently than once every four weeks. 25 mmol/L) in four weeks reduce the dose by approximately 25%. 5 mmol/L), a dose reduction should be considered.
If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
The haemoglobin should be measured every one or two weeks until it is stable. Thereafter the haemoglobin can be measured at longer intervals.
Maintenance phase:
In dialysis patients, Aranesp may continue to be administered as a single injection once weekly or once every two weeks. Dialysis patients converting from once weekly to once every other week dosing with Aranesp should initially receive a dose equivalent to twice the previous once weekly dose.
In patients not on dialysis, Aranesp may continue to be administered as a single injection once weekly or once every two weeks or once monthly. For patients treated with Aranesp once every two weeks, after the target haemoglobin has been achieved, Aranesp may then be administered subcutaneously once monthly using an initial dose equal to twice the previous once every two week dose.
Dosing should be titrated as necessary to maintain the haemoglobin target. If a dose adjustment is required to maintain haemoglobin at the desired level, it is recommended that the dose is adjusted by approximately 25%. 25 mmol/L) in four weeks reduce the dose by approximately 25%, depending on the rate of increase.
5 mmol/L), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
After any dose or schedule adjustment the haemoglobin should be monitored every one or two weeks. Dose changes in the maintenance phase of treatment should not be made more frequently than every two weeks. When changing the route of administration the same dose must be used and the haemoglobin monitored every one or two weeks so that the appropriate dose adjustments can be made to keep the haemoglobin at the desired level.
Clinical studies have demonstrated that adult patients receiving r-HuEPO one, two or three times weekly may be converted to once weekly or once every other week Aranesp. The initial weekly dose of Aranesp (mcg/week) can be determined by dividing the total weekly dose of r-HuEPO (IU/week) by 200.
The initial every other week dose of Aranesp (mcg/every other week) can be determined by dividing the total cumulative dose of r-HuEPO administered over a two-week period by 200. Because of individual variability, titration to optimal therapeutic doses is expected for individual patients.
When substituting Aranesp for r-HuEPO the haemoglobin should be monitored every one or two weeks and the same route of administration should be used. Paediatric population with chronic renal failure Treatment of paediatric […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised March 13, 2026[1]
The warnings and precautions information presented below includes both prefilled pen and prefilled syringe safety data. 4. Injection site pain was reported as attributable to treatment in studies where Aranesp was administered via subcutaneous injection.
The injection site discomfort was generally mild and transient in nature and occurred predominantly after the first injection. Tabulated list of adverse reactions Incidence of adverse reactions are listed below by system organ class and frequency.
Frequencies are defined as:
Very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data). Data are presented separately for CRF and cancer patients reflecting the different adverse reaction profile in these populations.
Chronic renal failure patients Data presented from controlled studies included 1,357 patients, 766 who received Aranesp and 591 patients who received r-HuEPO. In the Aranesp group, 83% were receiving dialysis and 17% were not receiving dialysis.
1). Incidence of adverse reactions from controlled clinical studies and post-marketing experience are: MedDRA system organ class Subject incidence Adverse reaction Blood and lymphatic system disorders Not known2 Pure red cell aplasia Immune system disorders Very common Hypersensitivitya Common Strokeb Nervous system disorders Uncommon1 Convulsions Cardiac disorders Very common Hypertension Uncommon Thromboembolic eventsc Vascular disorders Uncommon1 Dialysis vascular access thrombosisd Common Rash/erythemae Skin and subcutaneous tissue disorders Not known2 SJS/TEN, erythema multiforme, blistering, skin exfoliation Common Injection site painGeneral disorders and administration site conditions Uncommon1 Injection site bruising Injection site haemorrhage Source: Includes 5 randomised, double-blind, active-controlled studies (970200, 970235, 980117, 980202, and 980211) except for the adverse reaction of stroke which was identified as an adverse reaction in the TREAT study (study 20010184).
1 Adverse reactions identified in the post-marketing environment. Per the Guideline on Summary of Product Characteristics (Revision 2, September 2009), frequency of adverse reactions identified in the post-marketing setting was determined using the “Rule of three”.
2 Frequency cannot be estimated from the available data. a Hypersensitivity events includes all events under the hypersensitivity SMQ. b Stroke events includes PT haemorrhagic stroke, ischaemic stroke, cerebrovascular accident, and stroke in evolution.
c Thromboembolic events adverse reaction includes PT embolism arterial, thrombophlebitis, thrombosis, venous thrombosis limb. d Dialysis vascular access thrombosis includes all adverse reactions under the dialysis vascular access thrombosis AMQ e Rash/erythema adverse reaction includes PT rash, rash pruritic, rash macular, rash generalised, erythema.
Cancer patients Adverse reactions were determined based on pooled data from eight randomised, double-blind, placebo-controlled studies of Aranesp with a total of 4,630 patients (Aranesp 2,888, placebo 1,742). , lymphoma, multiple myeloma) were enrolled in the clinical studies.
Incidence of adverse reactions from controlled clinical studies and post-marketing experience are: MedDRA system organ class Subject incidence Adverse reaction Immune system disorders Very common Hypersensitivitya Nervous system disorders Uncommon1 Convulsions Cardiac disorders Common Hypertension Vascular disorders Common Thromboembolic eventsb, including pulmonary embolism Common Rash/erythemac Skin and subcutaneous tissue disorders Not known2 SJS/TEN, erythema multiforme, blistering, skin exfoliation Common Oedemad Common Injection site paine General disorders and administration site conditions Uncommon1 Injection site bruising Injection site haemorrhage 1 ADRs identified in the post marketing environment.
Per the Guideline on Summary of Product Characteristics (Revision 2, September 2009), frequency of ADRs identified in the post marketing setting was determined using the “Rule of three”. 2 Frequency cannot be estimated from the available data.
Source: includes 8 randomised, double-blind, placebo-controlled studies (980291-schedule 1 and 2, 980297, 990114, 20000161, 20010145, 20030232, and 20070782) a Hypersensitivity events includes all events under the hypersensitivity SMQ.
b Thromboembolic events adverse reactions includes PT embolism, thrombosis, deep vein thrombosis, jugular vein thrombosis, venous thrombosis, arterial thrombosis, pelvic venous thrombosis, peripheral embolism, pulmonary embolism, as well as thrombosis in device from SOC product issues.
c Rash adverse reactions includes PT rash, rash pruritic, rash generalised, rash papular, erythema, exfoliative rash, rash maculo-papular, rash vesicular as well as rash pustular from SOC Infections and Infestations. d Oedema: includes PT Oedema Peripheral, Oedema, Generalised Oedema, Oedema due to Cardiac Disease, Face oedema e Injection site pain adverse reaction includes PT injection site pain, administration site pain, catheter site pain, infusion site pain and vessel puncture site pain.
1). In isolated cases, neutralising anti-erythropoietin antibody mediated pure red cell aplasia (PRCA) associated with Aranesp therapy have been reported predominantly in patients with CRF […]
GBOfficial regulatory label· Warnings and precautions· revised March 13, 2026[1]
The warnings and precautions information presented below includes both prefilled pen and prefilled syringe safety data. General In order to improve the traceability of erythropoiesis-stimulating agents (ESAs), the trade name of the administered ESA should be clearly recorded (or stated) in the patient file.
Blood pressure should be monitored in all patients, particularly during initiation of Aranesp therapy. 2). Cases of severe hypertension, including hypertensive crisis, hypertensive encephalopathy, and seizures, have been observed in CRF patients treated with Aranesp.
In order to ensure effective erythropoiesis, iron status should be evaluated for all patients prior to and during treatment and supplementary iron therapy may be necessary. Non-response to therapy with Aranesp should prompt a search for causative factors.
Deficiencies of iron, folic acid or vitamin B12 reduce the effectiveness of ESAs and should therefore be corrected. Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminium toxicity, underlying haematologic diseases, or bone marrow fibrosis may also compromise the erythropoietic response.
A reticulocyte count should be considered as part of the evaluation. If typical causes of non-response are excluded, and the patient has reticulocytopenia, an examination of the bone marrow should be considered. If the bone marrow is consistent with PRCA, testing for anti-erythropoietin antibodies should be performed.
Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with epoetin treatment. More severe cases have been observed with long-acting epoetins.
At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Aranesp should be withdrawn immediately and an alternative treatment considered.
If the patient has developed a severe cutaneous skin reaction such as SJS or TEN due to the use of Aranesp, treatment with Aranesp must not be restarted in this patient at any time. Pure red cell aplasia caused by neutralising anti-erythropoietin antibodies has been reported in association with ESAs, including Aranesp.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised March 13, 2026[1]
1. Poorly controlled hypertension.
This is not medical advice. Consult a qualified healthcare professional.
o If appropriate, red blood cell transfusion should be the preferred treatment for the management of anemia in patients with a long life expectancy and who are receiving myelosuppressive chemotherapy. 1 Pediatrics Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.
2 Geriatrics Geriatrics (≥ 65 years of age): Chronic Kidney Disease Patients: The results of clinical trials with Aranesp suggest no increased safety risk with increasing age.
Cancer Patients:
No overall differences in safety or efficacy were observed between these patients and younger patients. 4 Geriatrics.
How to take
CAOfficial regulatory label· revised March 22, 2025[2]
). • Patients with uncontrolled hypertension should not be treated with Aranesp; blood pressure should be adequately controlled before initiation of therapy with Aranesp. • Aranesp should be used with caution in patients with a history of seizures.
• Antibody-mediated Pure Red Cell Aplasia (PRCA) has been reported after months to years of treatment with ESAs. Chronic Kidney Disease Patients • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target hemoglobin levels of 130 g/L and above.
Individualize dosing to achieve and maintain hemoglobin levels within the range of 100 to 115 g/L, not to exceed 120 g/L. Cancer Patients • ESAs increased the risks for death, serious adverse cardiovascular reactions and thromboembolic events in some controlled clinical trials.
• ESAs shortened overall survival and/or increased the risk of tumour progression or recurrence in some clinical studies in patients with breast, head and neck, lymphoid, cervical and non-small cell lung cancers when dosed to target a hemoglobin level of ≥ 120 g/L.
• To minimize the above risks, use the lowest dose needed to avoid red blood cell (RBC) transfusions. • Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy. Aranesp is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.
• If appropriate, red blood cell transfusion should be the preferred treatment for the management of anemia in patients with a long-life expectancy and who are receiving myelosuppressive chemotherapy. • Discontinue Aranesp following the completion of a chemotherapy course.
1 Dosing Considerations IMPORTANT: See 3 SERIOUS WARNINGS AND PRECAUTIONS BOX and 7 WARNINGS AND PRECAUTIONS: Increased Mortality, Serious Adverse Cardiovascular Reactions, Thromboembolic Events and Stroke. Aranesp dosing regimens are different for each of the indications described in the 1 INDICATIONS section of this Product Monograph.
Aranesp should be administered under the supervision of a healthcare professional. Due to the longer serum half-life, Aranesp should be administered less frequently than Epoetin alfa (for example, where Epoetin alfa is administered three times a week, Aranesp should be administered weekly).
When changing the route of administration, the same dose should be used and the hemoglobin monitored so that the appropriate dose adjustments can be made to keep the hemoglobin at the desired concentration. Chronic Kidney Disease Patients The dose should be started and slowly adjusted, as described in Section Recommended Dose and Dosage Adjustment, based on hemoglobin levels.
If a patient fails to respond or maintain a response, other etiologies should be considered and evaluated (see 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests; Lack or Loss of Response to Aranesp, Pure Red Cell Aplasia).
It should be recognized that subcutaneous administration of recombinant human proteins may increase the risk of immunogenicity. In patients on hemodialysis, the IV route is recommended. Correction of Anemia in Chronic Kidney Disease Patients The treatment of anemia in chronic renal failure patients should be individualized.
) as well as national guidelines. ESA therapy should only be initiated if hemoglobin is less than 100 g/L. Conversion to Aranesp from Recombinant Human Erythropoietin in CKD Patients The clinical studies demonstrated that the relationship between baseline rHuEPO and maintenance Aranesp is nonlinear across the dosing spectrum.
Consequently, the starting weekly dose of Aranesp should be estimated on the basis of the weekly Epoetin alfa dose at the time of substitution (see Table 1). Due to the longer serum half-life, Aranesp should be administered less frequently than rHuEPO.
Patients receiving rHuEPO 2 or 3 times weekly should change to once weekly Aranesp at a dose equivalent to their total weekly dose of rHuEPO. Patients receiving rHuEPO once per week should change to Aranesp once every 2 weeks at a dose that is equivalent to the sum of 2 weekly doses of rHuEPO.
The same route of administration should be used. For patients prescribed prefilled syringes the calculated dose should be rounded upward to the next available syringe strength. Aranesp® (darbepoetin alfa injection) Page 7 of 67 Table 1.
2 Recommended Dose and Dosage Adjustment, Dose Adjustment for Chronic Kidney Disease Patients). Data from approximately 800 patients receiving Aranesp in clinical studies were analyzed to assess the dose required to maintain hemoglobin; no difference was observed between the average weekly dose administered by the IV or SC routes of administration.
Because of intersubject variability, titration to the optimal therapeutic Aranesp dose is required for individual patients. 2 Recommended Dose and […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
1 Adverse Reaction Overview All Patients Thrombotic/Vascular Events The following thrombotic/vascular events have been reported in patients receiving ESAs (some with fatal outcomes): venous and arterial thromboses and embolism (such as deep venous thrombosis, arterial thrombosis, pulmonary emboli, aneurysms, retinal thrombosis, clotting of vascular access), cerebrovascular accidents (including cerebral infarction and cerebral hemorrhage) and transient ischemic attacks.
Chronic Kidney Disease Patients In all studies with CKD patients, the most frequently reported serious adverse reactions with Aranesp were vascular access thrombosis, congestive heart failure, sepsis, and cardiac arrhythmia. The most commonly reported adverse reactions were infection, hypertension, hypotension, myalgia, headache, and diarrhea (see 7 WARNINGS AND PRECAUTIONS, Increased Mortality, Serious Adverse Cardiovascular Reactions, Thromboembolic Events and Stroke).
, discontinuation of Aranesp, adjustment in dosage, or the need for concomitant medication to treat an adverse reaction symptom) were hypotension, hypertension, fever, myalgia, nausea, and chest pain. Cancer Patients Receiving Chemotherapy The most frequently reported serious adverse events included death, fever, pneumonia, dehydration, vomiting, and dyspnea.
2 Clinical Trial Adverse Reactions). 2 Clinical Trial Adverse Reactions). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. Chronic Kidney Disease Patients The data described below reflect exposure to Aranesp in 1598 CKD patients, including 675 exposed for at least 6 months, of whom 185 were exposed for greater than 1 year.
Aranesp was evaluated in active-controlled (n = 823) and uncontrolled studies (n = 775). The rates of adverse events and association with Aranesp are best assessed in the results from studies in which Aranesp was used to stimulate erythropoiesis in patients anemic at study baseline (n = 348), and, in particular, the subset of these patients in randomized controlled trials (n = 276).
Because there were no substantive differences in the rates of adverse reactions between these subpopulations, or between these subpopulations and the entire population of patients treated with Aranesp, data from all 1598 patients were pooled.
Aranesp® (darbepoetin alfa injection) Page 19 of 67 The population encompassed an age range from 18 to 91 years. Fifty-seven percent of the patients were male. The percentages of Caucasian, Black, Asian, and Hispanic patients were 83%, 11%, 3%, and 1%, respectively.
66 mcg/kg). Some of the adverse events reported are typically associated with CKD, or recognized complications of dialysis, and may not necessarily be attributable to Aranesp therapy. No important differences in adverse event rates between treatment groups were observed in controlled studies in which patients received Aranesp or other ESAs.
The data in Table 5 reflect those adverse events occurring in at least 5% of CKD patients treated with Aranesp. Table 5. Adverse Events Occurring in ≥ 5% of CKD Patients Event CKD Patients Treated With Aranesp (n = 1598) Application site Injection Site Pain 7% Body as a whole Peripheral Edema 11% Fatigue 9% Fever 9% Death 7% Chest Pain, Unspecified 6% Fluid Overload 6% Access Infection 6% Influenza-like Symptoms 6% Access Hemorrhage 6% Asthenia 5% Cardiovascular Hypertension 23% Hypotension 22% Cardiac Arrhythmias/Cardiac Arrest 10% Angina Pectoris/Cardiac Chest Pain 8% Thrombosis Vascular Access 8% Congestive Heart Failure 6% CNS/PNS Headache 16% Dizziness 8% Aranesp® (darbepoetin alfa injection) Page 20 of 67 Table 5.
Adverse Events Occurring in ≥ 5% of CKD Patients Event CKD Patients Treated With Aranesp (n = 1598) Gastrointestinal Diarrhea 16% Vomiting 15% Nausea 14% Abdominal Pain 12% Constipation 5% Musculoskeletal Myalgia 21% Arthralgia 11% Limb Pain 10% Back Pain 8% Resistance mechanism Infectiona 27% Respiratory Upper Respiratory Infection 14% Dyspnea 12% Cough 10% Bronchitis 6% Skin and appendages Pruritus 8% a Infection includes sepsis, bacteremia, pneumonia, peritonitis, and abscess.
The incidence rates for other clinically significant events are shown in Table 6. Table 6. 22 events per patient year of Aranesp therapy. , vascular access thrombosis, venous thrombosis, and pulmonary emboli) with Aranesp therapy were similar to those observed with rHuEPO therapy in these trials.
Cancer Patients Receiving Chemotherapy The data described below reflect the exposure to Aranesp in 873 cancer patients. Aranesp was evaluated in seven studies that were active-controlled and/or placebo-controlled studies of up to 6 months duration.
The Aranesp-treated patient demographics were as follows: median age of 63 years (range of 20 to 91 years); 40% male; 88% Caucasian, 5% Hispanic, 4% Black, and 3% Asian. Over 90% of patients had locally […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
, Increased Mortality, Serious Adverse Cardiovascular Reactions, Thromboembolic Events and Stroke, and 4 DOSAGE AND ADMINISTRATION). • Patients with uncontrolled hypertension should not be treated with Aranesp; blood pressure should be adequately controlled before initiation of therapy with Aranesp.
• Aranesp should be used with caution in patients with a history of seizures. • Antibody-mediated Pure Red Cell Aplasia (PRCA) has been reported after months to years of treatment with ESAs. Chronic Kidney Disease Patients • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target hemoglobin levels of 130 g/L and above.
Individualize dosing to achieve and maintain hemoglobin levels within the range of 100 to 115 g/L, not to exceed 120 g/L. Cancer Patients • ESAs increased the risks for death, serious adverse cardiovascular reactions and thromboembolic events in some controlled clinical trials.
• ESAs shortened overall survival and/or increased the risk of tumour progression or recurrence in some clinical studies in patients with breast, head and neck, lymphoid, cervical and non-small cell lung cancers when dosed to target a hemoglobin level of ≥ 120 g/L.
• To minimize the above risks, use the lowest dose needed to avoid red blood cell (RBC) transfusions. • Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy. Aranesp is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.
• If appropriate, red blood cell transfusion should be the preferred treatment for the management of anemia in patients with a long-life expectancy and who are receiving myelosuppressive chemotherapy. • Discontinue Aranesp following the completion of a chemotherapy course.
1 Dosing Considerations IMPORTANT: See 3 SERIOUS WARNINGS AND PRECAUTIONS BOX and 7 WARNINGS AND PRECAUTIONS: Increased Mortality, Serious Adverse Cardiovascular Reactions, Thromboembolic Events and Stroke. Aranesp dosing regimens are different for each of the indications described in the 1 INDICATIONS section of this Product Monograph.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
Aranesp is contraindicated in patients: • with uncontrolled hypertension • who develop Pure Red Cell Aplasia (PRCA) following treatment with any ESAs Aranesp® (darbepoetin alfa injection) Page 5 of 67 • with sensitivity to mammalian cell-derived products • with known hypersensitivity to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised March 8, 2026[3]
1 Important Dosing Information Evaluation of Iron Stores and Nutritional Factors Evaluate the iron status in all patients before and during treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%.
The majority of patients with CKD will require supplemental iron during the course of ESA therapy. ) before initiating Aranesp. Following initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin level is stable and sufficient to minimize the need for RBC transfusion.
2 Patients with Chronic Kidney Disease In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
No trial has identified a hemoglobin target level, Aranesp dose, or dosing strategy that does not increase these risks. 1 )] . Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events [see Boxed Warning and Clinical Studies ( 14 ) ] .
For all patients with CKD When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability.
A single hemoglobin excursion may not require a dosing change. Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments. , more than 1 g/dL in any 2-week period), reduce the dose of Aranesp by 25% or more as needed to reduce rapid responses.
For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. For patients who do not respond adequately over a 12-week escalation period, increasing the Aranesp dose further is unlikely to improve response and may increase risks.
Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Aranesp if responsiveness does not improve.
For adult patients with CKD on dialysis :
Initiate Aranesp treatment when the hemoglobin level is less than 10 g/dL. If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Aranesp. 75 mcg/kg once every 2 weeks as appropriate. The intravenous route is recommended for patients on hemodialysis.
For adult patients with CKD not on dialysis :
Consider initiating Aranesp treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply: ° The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and , ° Reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal.
If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of Aranesp, and use the lowest dose of Aranesp sufficient to reduce the need for RBC transfusions. 45 mcg/kg body weight intravenously or subcutaneously given once at four week intervals as appropriate.
For pediatric patients with CKD :
Initiate Aranesp treatment when the hemoglobin level is less than 10 g/dL. If the hemoglobin level approaches or exceeds 12 g/dL, reduce or interrupt the dose of Aranesp. 75 mcg/kg once every 2 weeks. 2 ) . Conversion from Epoetin alfa to Aranesp in patients with CKD on dialysis Aranesp is administered less frequently than epoetin alfa.
Administer Aranesp once weekly in patients who were receiving epoetin alfa 2 to 3 times weekly. Administer Aranesp once every 2 weeks in patients who were receiving epoetin alfa once weekly. Estimate the starting weekly dose of Aranesp for adults and pediatric patients on the basis of the weekly epoetin alfa dose at the time of substitution (see Table 1).
Maintain the route of administration (intravenous or subcutaneous injection). Table 1. 5 10 5,000 to 10,999 25 20 11,000 to 17,999 40 40 18,000 to 33,999 60 60 34,000 to 89,999 100 100 ≥ 90,000 200 200 *For pediatric patients receiving a weekly epoetin alfa dose of < 1,500 Units/week, the available data are insufficient to determine an Aranesp conversion dose.
Conversion from Epoetin alfa to Aranesp in patients with CKD not on dialysis Refer to Table 1. The dose conversion depicted in Table 1 does not accurately estimate the once monthly dose of Aranesp. 3 Patients on Cancer Chemotherapy Initiate Aranesp in patients on cancer chemotherapy only if the hemoglobin is less than 10 g/dL, and if there is a minimum of two additional months of planned chemotherapy.
Use the lowest dose of Aranesp necessary to avoid RBC transfusions. 25 mcg/kg every week subcutaneously until completion of a chemotherapy course. 500 mcg every 3 weeks subcutaneously until completion of a chemotherapy course. Table 2.
4 Preparation and Administration The needle cover of the prefilled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions. Do not shake. Do not use Aranesp that has been shaken or frozen. Protect vials and prefilled syringes from light.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials or prefilled syringes exhibiting particulate matter or discoloration. Discard unused portion of Aranesp in vials or prefilled syringes.
Do not re-enter vial. Do not dilute Aranesp and do not administer in conjunction with other drug solutions. Self-Administration of the Prefilled Syringe Training should aim to demonstrate to those patients and caregivers how to measure the dose of Aranesp, and the focus should be on ensuring that a patient or caregiver can successfully perform all of the steps in the Instructions for Use for a prefilled syringe.
If a patient or caregiver is not able to demonstrate that they can measure the dose and administer the product successfully, you should consider whether the patient is an appropriate candidate for self-administration of Aranesp or whether the patient would benefit from a different Aranesp presentation.
If a patient or caregiver experiences difficulty measuring the required dose, especially if it is other than the entire contents of the Aranesp prefilled syringe, use of the Aranesp vial may be considered.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 1,096 reports total. [5]
Death 189
Off Label Use 156
Hospitalisation 97
Anaemia 83
Drug Ineffective 61
Condition Aggravated 59
Gout 59
Blood Creatinine Increased 58
End Stage Renal Disease 58
Abdominal Pain 57
Oedema Peripheral 57
General Physical Health Deterioration 55
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised March 8, 2026[3]
1 ). 1 ). gov/medwatch. 1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
Patients with Chronic Kidney Disease Adult Patients Adverse reactions were determined based on pooled data from 5 randomized, active-controlled studies of Aranesp with a total of 1357 patients (Aranesp 766, epoetin alfa 591). The median duration of exposure for patients receiving Aranesp was 340 days, with 580 patients exposed for greater than 6 months and 360 patients exposed for greater than 1 year.
81). The median (range) age for patients administered Aranesp was 62 years (18 to 88). In the Aranesp group, 55% were male, 72% were white, 83% were receiving dialysis, and 17% were not receiving dialysis. Table 5 lists adverse reactions occurring in ≥ 5% of patients treated with Aranesp.
Table 5. Adverse Reactions Occurring in ≥ 5% of Patients with CKD Adverse Reaction Patients Treated w ith Aranesp (n = 766) Hypertension 31% Dyspnea 17% Peripheral edema 17% Cough 12% Procedural hypotension 10% Angina pectoris 8% Vascular access complications 8% Fluid overload 7% Rash/Erythema 5% Arteriovenous graft thrombosis 5% Rates of adverse reactions with Aranesp therapy were similar to those observed with other recombinant erythropoietins in these studies.
1 )] . In one study, Aranesp was administered to 81 pediatric patients with CKD who had stable hemoglobin concentrations while previously receiving epoetin alfa. In a second study, Aranesp was administered to 114 anemic pediatric patients with CKD receiving or not receiving dialysis for initial treatment of anemia.
In these studies, the most frequently reported serious adverse reactions with Aranesp were hypertension and convulsions. The most commonly reported adverse reactions were hypertension, injection site pain, rash, and convulsions. Aranesp administration was discontinued because of injection site pain in 2 patients and hypertension in 3 patients.
Patients with Cancer Receiving Chemotherapy Adverse reactions were based on data from a randomized, double-blind, placebo-controlled study of Aranesp in 597 patients (Aranesp 301, placebo 296) with extensive stage small cell lung cancer (SCLC) receiving platinum-based chemotherapy.
All patients were white, 64% were male, and the median age was 61 years (range: 28 to 82 years); 25% of the study population were from North America, Western Europe, and Australia. Patients received Aranesp at a dose of 300 mcg or placebo weekly for 4 weeks then every 3 weeks for a total of 24 weeks, and the median duration of exposure was 19 weeks (range: 1 to 26 weeks).
Adverse reactions were also based on data from 7 randomized, double-blind, placebo-controlled studies, including the SCLC study described above, that enrolled 2112 patients (Aranesp 1203, placebo 909) with non-myeloid malignancies.
Most patients were white (95%), male (52%), and the median age was 63 years (range: 18 to 91 years); 73% of the study population were from North America, Western Europe, and Australia. Dosing and schedules varied by study from once weekly to once every 4 weeks, and the median duration of exposure was 12 weeks (range: 1 to 27 weeks).
Table 6. 3%) * “Cerebrovascular disorders” encompasses central nervous system (CNS) hemorrhages and cerebrovascular accidents (ischemic and hemorrhagic). ” In addition to the thrombovascular adverse reactions, abdominal pain and edema occurred at a higher incidence in patients taking Aranesp compared to patients on placebo.
2% vs. 8% vs. 7%) were reported more frequently in patients receiving Aranesp compared to the placebo group. 3% vs. 6% vs. 1%) in the Aranesp-treated patients compared to those receiving placebo. 2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of Aranesp.
Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 3 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity.
In clinical studies, the percentage of patients with antibodies to Aranesp was examined using the Biacore ® assay. Sera from 1501 patients with CKD and 1159 patients with cancer were tested. At baseline, prior to Aranesp treatment, binding antibodies were detected in 59 patients (4%) with CKD and 36 patients with cancer (3%).
During Aranesp therapy (range: 22 to 177 weeks), a follow-up sample was taken. One additional patient with CKD and 8 additional patients with cancer developed antibodies capable of binding Aranesp. In two studies of pediatric patients with CKD aged 2-16, 20 of 111 patients with CKD (18%) receiving dialysis and 6 of 69 patients (9%) not receiving dialysis had anti-ESA antibodies at baseline.
During therapy, 4 additional patients receiving dialysis and 4 additional patients not receiving dialysis developed antibodies capable of binding Aranesp. None of the patients had antibodies capable of neutralizing the activity of Aranesp or endogenous erythropoietin at baseline or at end of study.
No clinical sequelae consistent with PRCA were associated with the presence of these antibodies. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies to Aranesp with the incidence of antibodies to other products may be misleading. 6 ) ] .
USOfficial regulatory label· Warnings and precautions· revised March 8, 2026[3]
1 ). 1 ). 2 ). 3 ). 4 ). 4 ). 6 ). 7 ). 8 ). 3 g/dL), Aranesp and other ESAs increased the risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of hemodialysis vascular access, and other thromboembolic events in the higher target groups.
1 )] . 2 )] . Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks.
In controlled clinical trials of patients with cancer, Aranesp and other ESAs increased the risks for death and serious adverse cardiovascular reactions. These adverse reactions included myocardial infarction and stroke. In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.
The design and overall results of the 3 large trials comparing higher and lower hemoglobin targets are shown in Table 3. Table 3. Randomized Controlled Trials Showing Adverse Cardiovascular Outcomes in Patients with CKD Normal Hematocrit Study (NHS) (N = 12 65 ) CHOIR (N = 1432) TREAT (N = 4038) Time Period of Trial 1993 to 1996 2003 to 2006 2004 to 2009 Population Adult patients with CKD on hemodialysis with coexisting CHF or CAD, hematocrit 30 ± 3% on epoetin alfa Adult patients with CKD not on dialysis with hemoglobin < 11 g/dL not previously administered epoetin alfa Adult patients with CKD not on dialysis with type II diabetes, hemoglobin ≤ 11 g/dL Hemoglobin Target; Higher vs.
0 vs. 5 vs. 0 vs. 3) vs. 4) vs. 8) vs. 68) Patients with Chronic Kidney Disease Normal Hematocrit Study (NHS): A prospective, randomized, open-label study of 1265 patients with chronic kidney disease on dialysis with documented evidence of congestive heart failure or ischemic heart disease was designed to test the hypothesis that a higher target hematocrit (Hct) would result in improved outcomes compared with a lower target Hct.
In this study, patients were randomized to epoetin alfa treatment targeted to a maintenance hemoglobin of either 14 ± 1 g/dL or 10 ± 1 g/dL. The trial was terminated early with adverse safety findings of higher mortality in the high hematocrit target group.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised March 8, 2026[3]
3 )] . 6 )] . 7 )] . Uncontrolled hypertension ( 4 ) Pure red cell aplasia (PRCA) that begins after treatment with Aranesp or other erythropoietin protein drugs ( 4 ) Serious allergic reactions to Aranesp ( 4 )
This is not medical advice. Consult a qualified healthcare professional.
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 Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary.
5 mmol/L). Subcutaneous use is preferable in patients who are not receiving haemodialysis to avoid the puncture of peripheral veins. 5 mmol/L). Caution should be exercised with escalation of Aranesp doses in patients with chronic renal failure.
1). Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. 5 mmol/L). 5 mmol/L) are observed are described below. 25 mmol/L) over a four week period should be avoided.
If it occurs, appropriate dose adjustment should be made as provided. Treatment with Aranesp is divided into two stages, correction and maintenance phase. Guidance is given separately for adult and paediatric patients. 45 mcg/kg body weight, as a single injection once weekly.
5 mcg/kg once monthly. 6 mmol/L) in four weeks) increase the dose by approximately 25%. Dose increases must not be made more frequently than once every four weeks. 25 mmol/L) in four weeks reduce the dose by approximately 25%. 5 mmol/L), a dose reduction should be considered.
If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
The haemoglobin should be measured every one or two weeks until it is stable. Thereafter the haemoglobin can be measured at longer intervals.
Maintenance phase:
In dialysis patients, Aranesp may continue to be administered as a single injection once weekly or once every two weeks. Dialysis patients converting from once weekly to once every other week dosing with Aranesp should initially receive a dose equivalent to twice the previous once weekly dose.
In patients not on dialysis, Aranesp may continue to be administered as a single injection once weekly or once every two weeks or once monthly. For patients treated with Aranesp once every two weeks, after the target haemoglobin has been achieved, Aranesp may then be administered subcutaneously once monthly using an initial dose equal to twice the previous once every two week dose.
Dosing should be titrated as necessary to maintain the haemoglobin target. If a dose adjustment is required to maintain haemoglobin at the desired level, it is recommended that the dose is adjusted by approximately 25%. 25 mmol/L) in four weeks reduce the dose by approximately 25%, depending on the rate of increase.
5 mmol/L), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
After any dose or schedule adjustment the haemoglobin should be monitored every one or two weeks. Dose changes in the maintenance phase of treatment should not be made more frequently than every two weeks. When changing the route of administration the same dose must be used and the haemoglobin monitored every one or two weeks so that the appropriate dose adjustments can be made to keep the haemoglobin at the desired level.
Clinical studies have demonstrated that adult patients receiving r-HuEPO one, two or three times weekly may be converted to once weekly or once every other week Aranesp. The initial weekly dose of Aranesp (mcg/week) can be determined by dividing the total weekly dose of r-HuEPO (IU/week) by 200.
The initial every other week dose of Aranesp (mcg/every other week) can be determined by 6 dividing the total cumulative dose of r-HuEPO administered over a two-week period by 200. Because of individual variability, titration to optimal therapeutic doses is expected for individual patients.
When substituting Aranesp for r-HuEPO the haemoglobin should be monitored every one or two weeks and the same route of administration should be used. Paediatric population with chronic renal failure Treatment of […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised January 13, 2026[4]
4. Injection site pain was reported as attributable to treatment in studies where Aranesp was administered via subcutaneous injection. The injection site discomfort was generally mild and transient in nature and occurred predominantly after the first injection.
Tabulated list of adverse reactions Incidence of adverse reactions are listed below by system organ class and frequency.
Frequencies are defined as:
Very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data). Data are presented separately for CRF and cancer patients reflecting the different adverse reaction profile in these populations.
12 Chronic renal failure patients Data presented from controlled studies included 1,357 patients, 766 who received Aranesp and 591 patients who received r-HuEPO. In the Aranesp group, 83% were receiving dialysis and 17% were not receiving dialysis.
1). Incidence of adverse reactions from controlled clinical studies and post-marketing experience are: MedDRA system organ class Subject incidence Adverse reaction Blood and lymphatic system disorders Not known2 Pure red cell aplasia Immune system disorders Very common Hypersensitivitya Nervous system disorders Common Strokeb Uncommon1 Convulsions Cardiac disorders Very common Hypertension Vascular disorders Uncommon Thromboembolic eventsc Uncommon1 Dialysis vascular access thrombosisd Skin and subcutaneous tissue disorders Common Rash/erythemae Not known2 SJS/TEN, erythema multiforme, blistering, skin exfoliation General disorders and administration site conditions Common Injection site pain Uncommon1 Injection site bruising Injection site haemorrhage Source: Includes 5 randomised, double-blind, active-controlled studies (970200, 970235, 980117, 980202, and 980211) except for the adverse reaction of stroke which was identified as an adverse reaction in the TREAT study (study 20010184).
1 Adverse reactions identified in the post-marketing environment. Per the Guideline on Summary of Product Characteristics (Revision 2, September 2009), frequency of adverse reactions identified in the post-marketing setting was determined using the “Rule of three”.
2 Frequency cannot be estimated from the available data. a Hypersensitivity events includes all events under the hypersensitivity SMQ. b Stroke events includes PT haemorrhagic stroke, ischaemic stroke, cerebrovascular accident, and stroke in evolution.
c Thromboembolic events adverse reaction includes PT embolism arterial, thrombophlebitis, thrombosis, venous thrombosis limb. d Dialysis vascular access thrombosis includes all adverse reactions under the dialysis vascular access thrombosis AMQ e Rash/erythema adverse reaction includes PT rash, rash pruritic, rash macular, rash generalised, erythema.
Cancer patients Adverse reactions were determined based on pooled data from eight randomised, double-blind, placebo-controlled studies of Aranesp with a total of 4,630 patients (Aranesp 2,888, placebo 1,742). , lymphoma, multiple myeloma) were enrolled in the clinical studies.
Incidence of adverse reactions from controlled clinical studies and post-marketing experience are: MedDRA system organ class Subject incidence Adverse reaction Immune system disorders Very common Hypersensitivitya Nervous system disorders Uncommon1 Convulsions Cardiac disorders Common Hypertension Vascular disorders Common Thromboembolic eventsb, including pulmonary embolism 13 MedDRA system organ class Subject incidence Adverse reaction Skin and subcutaneous tissue disorders Common Rash/erythemac Not known2 SJS/TEN, erythema multiforme, blistering, skin exfoliation General disorders and administration site conditions Common Oedemad Common Injection site paine Uncommon1 Injection site bruising Injection site haemorrhage 1 ADRs identified in the post marketing environment.
Per the Guideline on Summary of Product Characteristics (Revision 2, September 2009), frequency of ADRs identified in the post marketing setting was determined using the “Rule of three”. 2 Frequency cannot be estimated from the available data.
Source: includes 8 randomised, double-blind, placebo-controlled studies (980291-schedule 1 and 2, 980297, 990114, 20000161, 20010145, 20030232, and 20070782) a Hypersensitivity events includes all events under the hypersensitivity SMQ.
b Thromboembolic events adverse reactions includes PT embolism, thrombosis, deep vein thrombosis, jugular vein thrombosis, venous thrombosis, arterial thrombosis, pelvic venous thrombosis, peripheral embolism, pulmonary embolism, as well as thrombosis in device from SOC product issues.
c Rash adverse reactions includes PT rash, rash pruritic, rash generalised, rash papular, erythema, exfoliative rash, rash maculo-papular, rash vesicular as well as rash pustular from SOC Infections and Infestations. d Oedema: includes PT Oedema Peripheral, Oedema, Generalised Oedema, Oedema due to Cardiac Disease, Face oedema e Injection site pain adverse reaction includes PT injection site pain, administration site pain, catheter site pain, infusion site pain and vessel puncture site pain.
1). In isolated cases, neutralising anti-erythropoietin antibody mediated pure red cell aplasia (PRCA) associated with Aranesp therapy have been reported predominantly in patients with CRF treated subcutaneously. In case PRCA is diagnosed, therapy […]
EUOfficial regulatory label· Warnings and precautions· revised January 13, 2026[4]
General In order to improve the traceability of erythropoiesis-stimulating agents (ESAs), the trade name of the administered ESA should be clearly recorded (or stated) in the patient file. Blood pressure should be monitored in all patients, particularly during initiation of Aranesp therapy.
2). Cases of severe hypertension, including hypertensive crisis, hypertensive encephalopathy, and seizures, have been observed in CRF patients treated with Aranesp. In order to ensure effective erythropoiesis, iron status should be evaluated for all patients prior to and during treatment and supplementary iron therapy may be necessary.
Non-response to therapy with Aranesp should prompt a search for causative factors. Deficiencies of iron, folic acid or vitamin B12 reduce the effectiveness of ESAs and should therefore be corrected. Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminium toxicity, underlying haematologic diseases, or bone marrow fibrosis may also compromise the erythropoietic response.
A reticulocyte count should be considered as part of the evaluation. If typical causes of non-response are excluded, and the patient has reticulocytopenia, an examination of the bone marrow should be considered. If the bone marrow is consistent with PRCA, testing for anti-erythropoietin antibodies should be performed.
9 Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with epoetin treatment. More severe cases have been observed with long-acting epoetins.
At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Aranesp should be withdrawn immediately and an alternative treatment considered.
If the patient has developed a severe cutaneous skin reaction such as SJS or TEN due to the use of Aranesp, treatment with Aranesp must not be restarted in this patient at any time. Pure red cell aplasia caused by neutralising anti-erythropoietin antibodies has been reported in association with ESAs, including Aranesp.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised January 13, 2026[4]
1. Poorly controlled hypertension.
This is not medical advice. Consult a qualified healthcare professional.
This has been predominantly reported in patients with CRF treated subcutaneously. 8). A paradoxical decrease in haemoglobin and development of severe anaemia associated with low reticulocyte counts should prompt to discontinue treatment with epoetin and perform anti-erythropoietin antibody testing.
Cases have been reported in patients with hepatitis C treated with interferon and ribavirin, when epoetins are used concomitantly. Epoetins are not approved in the management of anaemia associated with hepatitis C. Active liver disease was an exclusion criteria in all studies of Aranesp, therefore no data are available from patients with impaired liver function.
Since the liver is thought to be the principal route of elimination of darbepoetin alfa and r-HuEPO, Aranesp should be used with caution in patients with liver disease. Aranesp should also be used with caution in those patients with sickle cell anaemia.
Misuse of Aranesp by healthy persons may lead to an excessive increase in packed cell volume. This may be associated with life-threatening complications of the cardiovascular system. The needle cap of the pre-filled syringe or pre-filled pen contains dry natural rubber (a derivative of latex), which may cause allergic reactions.
Aranesp should be used with caution in patients with epilepsy. Convulsions have been reported in patients receiving Aranesp. , deep venous thrombosis, pulmonary embolism, and cerebral vascular accident). This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.
2. 5 mmol/L). Caution should be exercised with escalation of Aranesp doses in patients with chronic renal failure, since high cumulative epoetin doses may be associated with an increased risk of mortality, serious cardiovascular and cerebrovascular events.
1). Controlled clinical trials have not shown significant benefits attributable to the administration of epoetins when haemoglobin concentration is increased beyond the level necessary to control symptoms of anaemia and to avoid blood transfusion.
Supplementary iron therapy is recommended for all patients with serum ferritin values below 100 mcg/L or whose transferrin saturation is below 20%. Serum potassium levels should be monitored regularly during Aranesp therapy. Potassium elevation has been reported in a few patients receiving Aranesp, […]
Aranesp should be administered under the supervision of a healthcare professional. Due to the longer serum half-life, Aranesp should be administered less frequently than Epoetin alfa (for example, where Epoetin alfa is administered three times a week, Aranesp should be administered weekly).
When changing the route of administration, the same dose should be used and the hemoglobin monitored so that the appropriate dose adjustments can be made to keep the hemoglobin at the desired concentration. Chronic Kidney Disease Patients The dose should be started and slowly adjusted, as described in Section Recommended Dose and Dosage Adjustment, based on hemoglobin levels.
If a patient fails to respond or maintain a response, other etiologies should be considered and evaluated (see 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests; Lack or Loss of Response to Aranesp, Pure Red Cell Aplasia).
It should be recognized that subcutaneous administration of recombinant human proteins may increase the risk of immunogenicity. In patients on hemodialysis, the IV route is recommended. Correction of Anemia in Chronic Kidney Disease Patients The treatment of anemia in chronic renal failure patients should be individualized.
) as well as national guidelines. ESA therapy should only be initiated if hemoglobin is less than 100 g/L. Conversion to Aranesp from Recombinant Human Erythropoietin in CKD Patients The clinical studies demonstrated that the relationship between baseline rHuEPO and maintenance Aranesp is nonlinear across the dosing spectrum.
Consequently, the starting weekly dose of Aranesp should be estimated on the basis of the weekly Epoetin alfa dose at the time of substitution (see Table 1). Due to the longer serum half-life, Aranesp should be administered less frequently than rHuEPO.
Patients receiving rHuEPO 2 or 3 times weekly should change to once weekly Aranesp at a dose equivalent to their total weekly dose of rHuEPO. Patients receiving rHuEPO once per week should change to Aranesp once every 2 weeks at a dose that is equivalent to the sum of 2 weekly doses of rHuEPO.
The same route of administration should be used. For patients prescribed prefilled syringes the calculated dose should be rounded upward to the next available syringe strength. Aranesp® (darbepoetin alfa injection) Page 7 of 67 Table 1.
2 Recommended Dose and Dosage Adjustment, Dose Adjustment for Chronic Kidney Disease Patients). Data from approximately 800 patients receiving Aranesp in clinical studies were analyzed to assess the dose required to maintain hemoglobin; no difference was observed between the average weekly dose administered by the IV or SC routes of administration.
Because of intersubject variability, titration to the optimal therapeutic Aranesp dose is required for individual patients. When a patient’s hemoglobin is stabilized […]
Higher mortality (35% vs. 29%) was observed for the patients randomized to a target hemoglobin of 14 g/dL than for the patients randomized to a target hemoglobin of 10 g/dL. 018. The incidence of nonfatal myocardial infarction, vascular access thrombosis, and other thrombotic events was also higher in the group randomized to a target hemoglobin of 14 g/dL.
3 g/dL. The trial was terminated early with adverse safety findings. 03].
TREAT:
A randomized, double-blind, placebo-controlled, prospective trial of 4038 patients with CKD not on dialysis (eGFR of 20 – 60 mL/min), anemia (hemoglobin levels ≤ 11 g/dL), and type 2 diabetes mellitus, patients were randomized to receive either Aranesp treatment or a matching placebo.
Placebo group patients also received Aranesp when their hemoglobin levels were below 9 g/dL. The trial objectives were to demonstrate the benefit of Aranesp treatment of the anemia to a target hemoglobin level of 13 g/dL, when compared to a "placebo" group, by reducing the occurrence of either of two primary endpoints: (1) a composite cardiovascular endpoint of all-cause mortality or a specified cardiovascular event (myocardial ischemia, CHF, MI, and CVA) or (2) a composite renal endpoint of all-cause mortality or progression to end stage renal disease.
1% vs. 001. 54. Also, among Aranesp-treated subjects with a past history of cancer, there were more deaths due to all causes and more deaths adjudicated as due to cancer, in comparison with the control group. Patients with Cancer An increased incidence of thromboembolic reactions, some serious and life-threatening, occurred in patients with cancer treated with ESAs.
2 ) ] ) of 939 women with metastatic breast cancer receiving chemotherapy, patients received either weekly epoetin alfa or placebo for up to a year. This study was designed to show that survival was superior when epoetin alfa was administered to prevent anemia (maintain hemoglobin levels between 12 and 14 g/dL or hematocrit between 36% and 42%).
7% vs. 1% vs. 2%) in the first 4 months of the study among patients treated with epoetin alfa. Based on Kaplan-Meier estimates, at the time of study termination, the 12-month survival was lower in the epoetin alfa group than in the placebo group (70% vs.
012). Patients Having Surgery Aranesp is not approved for reduction of RBC transfusions in patients scheduled for surgical procedures. An increased incidence of DVT in patients receiving epoetin alfa undergoing surgical orthopedic procedures was demonstrated.
In a randomized, controlled study, 680 adult patients, not receiving prophylactic anticoagulation and undergoing spinal surgery, received epoetin alfa and standard of care (SOC) treatment (n = 340) or SOC treatment alone (n = 340).
1%] patients). 1%] in the SOC group). Increased mortality was observed in a randomized, placebo-controlled study of epoetin alfa in adult patients who were undergoing CABG surgery (7 deaths in 126 patients randomized to epoetin alfa versus no deaths among 56 patients receiving placebo).
Four of these deaths occurred during the period of study drug administration and all 4 deaths were associated with thrombotic events. 2 Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence in Patients with Cancer ESAs resulted in decreased locoregional control/progression-free survival (PFS) and/or overall survival (OS) (see Table 4).
Adverse effects on PFS and/or OS were observed in studies of patients receiving chemotherapy for breast cancer (Studies 1, 2, and 4), lymphoid malignancy (Study 3), and cervical cancer (Study 5); in patients with advanced head and neck cancer receiving radiation therapy (Studies 6 and 7), and in patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy (Studies 8 and 9).
Table 4. 8 g/dL RBC transfusions Decreased overall survival *Q1 = 25 th percentile Q3 = 75 th percentile † This study did not include a defined hemoglobin target. Doses were titrated to achieve and maintain the lowest hemoglobin level sufficient to avoid transfusion and not to exceed 12 g/dL.
1 ) ] . 7% vs. 4%) was significantly higher in the epoetin alfa arm. The most common investigator-attributed cause of death within the first 4 months was disease progression; 28 of 41 deaths in the epoetin alfa arm and 13 of 16 deaths in the placebo arm were attributed to disease progression.
Investigator-assessed time to tumor progression was not different between the 2 groups. Survival at 12 months was significantly lower in the epoetin alfa arm (70% vs. 012). Study 3 was a randomized, double-blind study (darbepoetin alfa vs.
placebo) conducted in 344 anemic patients with lymphoid malignancy receiving chemotherapy. 82). Study 8 was a multicenter, randomized, double-blind study (epoetin alfa vs. placebo) in which patients with advanced non-small cell lung cancer receiving only palliative radiotherapy or no active therapy were treated with epoetin alfa to achieve and maintain hemoglobin levels between 12 and 14 g/dL.
Following an interim analysis of 70 patients (planned accrual 300 patients), a significant difference in survival in favor of the patients in the placebo arm of the study was observed (median survival 63 vs. 04). Study 9 was a randomized, double-blind study (darbepoetin alfa vs.
placebo) in 989 anemic patients with active malignant disease, neither receiving nor planning to receive chemotherapy or radiation therapy. There was no evidence of a statistically significant reduction in proportion of patients receiving RBC transfusions.
The median survival was shorter in the darbepoetin alfa treatment group than in the placebo group (8 months vs. 57). Decreased Progression - free Survival and Overall Survival Study 1 was a randomized, open-label, multicenter study in 2,098 anemic women with metastatic breast cancer, who received first line or second line chemotherapy.
This was a non-inferiority study designed to rule out a 15% risk increase in tumor progression or death of epoetin alfa plus standard of care (SOC) as compared with SOC alone. 20), indicating the study objective was not met. There were more deaths from disease progression in the epoetin alfa plus SOC arm (59% vs.
56%) and more thrombotic vascular events in the epoetin alfa plus SOC arm (3% vs. 1%). 8% of subjects in the SOC group). 18). Study 4 was a randomized, open-label, controlled, factorial design study in which darbepoetin alfa was administered to prevent anemia in 733 women receiving neo-adjuvant breast cancer treatment.
A final analysis was performed after a median follow-up of approximately 3 years. The 3-year survival rate was lower (86% vs. 18) and the 3-year relapse-free survival rate was lower (72% vs. 79) in the darbepoetin alfa-treated arm compared to the control arm.
Study 5 was a randomized, open-label, controlled study that enrolled 114 of a planned 460 patients with cervical cancer receiving chemotherapy and radiotherapy. Patients were randomized to receive epoetin alfa to maintain hemoglobin between 12 and 14 g/dL or to RBC transfusion support as needed.
The study was terminated prematurely due to an increase in thromboembolic adverse reactions in epoetin alfa-treated patients compared to control (19% vs. 9%). Both local recurrence (21% vs. 20%) and distant recurrence (12% vs. 7%) were more frequent in epoetin alfa-treated patients compared to control.
Progression-free survival at 3 years was lower in the epoetin alfa-treated group compared to control (59% vs. 91). Overall survival at 3 years was lower in the epoetin alfa-treated group compared to control (61% vs. 42). Study 6 was a randomized, placebo-controlled study in 351 patients with head and neck cancer where epoetin beta or placebo was administered to achieve target hemoglobins ≥ 14 and ≥ 15 g/dL for women and men, respectively.
0008) with medians of 406 days and 745 days in the epoetin beta and placebo arms respectively. 02). 5 g/dL or no darbepoetin alfa. 02). 08). 0 g/dL, were randomized 2:1 to Aranesp or placebo and treated to a maximum Hb of 12 g/dL. Non-inferiority of Aranesp versus placebo was shown for overall survival (OS) and progression-free survival (PFS).
The study was designed to rule out a 15% risk increase. 01). 05). Aranesp did not demonstrate superiority to placebo for OS or PFS. 1% placebo). 1 )]. 3 Hypertension Aranesp is contraindicated in patients with uncontrolled hypertension. In Aranesp clinical studies, approximately 40% of patients with CKD required initiation or intensification of antihypertensive therapy during the early phase of treatment.
Hypertensive encephalopathy and seizures have been reported in patients with CKD receiving Aranesp. Appropriately control hypertension prior to initiation of and during treatment with Aranesp. Reduce or withhold Aranesp if blood pressure becomes difficult to control.
Advise patients of the importance of compliance with antihypertensive therapy and dietary restrictions [ see Patient Counseling Information ( 17 ) ] . 4 Seizures Aranesp increases the risk of seizures in patients with CKD. During the first several months following initiation of Aranesp, monitor patients closely for premonitory neurologic symptoms.
Advise patients to contact their healthcare practitioner for new-onset seizures, premonitory symptoms, or change in seizure frequency. , iron deficiency, infection, inflammation, bleeding). 6 ) ] . 2 )] . 6 Pure Red Cell Aplasia Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in patients treated with Aranesp.
This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration. PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which Aranesp is not approved).
If severe anemia and low reticulocyte count develop during treatment with Aranesp, withhold Aranesp and evaluate patients for neutralizing antibodies to erythropoietin. Contact Amgen (1-800-77-AMGEN) to perform assays for binding and neutralizing antibodies.
Permanently discontinue Aranesp in patients who develop PRCA following treatment with Aranesp or other erythropoietin protein drugs. Do not switch patients to other ESAs. 7 Serious Allergic Reactions Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur with Aranesp.
Immediately and permanently discontinue Aranesp and administer appropriate therapy if a serious allergic or anaphylactic reaction occurs. 8 Severe Cutaneous Reactions Blistering and skin exfoliation reactions including Erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with ESAs (including Aranesp) in the post-marketing setting.
Discontinue Aranesp therapy immediately if a severe cutaneous reaction, such as SJS/TEN, is suspected. 9 Dialysis Management Patients may require adjustments in their dialysis prescriptions after initiation of Aranesp. Patients receiving Aranesp may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.
This has been predominantly reported in patients with CRF treated subcutaneously. 8). A paradoxical decrease in haemoglobin and development of severe anaemia associated with low reticulocyte counts should prompt to discontinue treatment with epoetin and perform anti-erythropoietin antibody testing.
Cases have been reported in patients with hepatitis C treated with interferon and ribavirin, when epoetins are used concomitantly. Epoetins are not approved in the management of anaemia associated with hepatitis C. Active liver disease was an exclusion criteria in all studies of Aranesp, therefore no data are available from patients with impaired liver function.
Since the liver is thought to be the principal route of elimination of darbepoetin alfa and r-HuEPO, Aranesp should be used with caution in patients with liver disease. Aranesp should also be used with caution in those patients with sickle cell anaemia.
Misuse of Aranesp by healthy persons may lead to an excessive increase in packed cell volume. This may be associated with life-threatening complications of the cardiovascular system. The needle cap of the pre-filled syringe or pre-filled pen contains dry natural rubber (a derivative of latex), which may cause allergic reactions.
Aranesp should be used with caution in patients with epilepsy. Convulsions have been reported in patients receiving Aranesp. , deep venous thrombosis, pulmonary embolism, and cerebral vascular accident). This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.
2. 5 mmol/L). Caution should be exercised with escalation of Aranesp doses in patients with chronic renal failure, since high cumulative epoetin doses may be associated with an increased risk of mortality, serious cardiovascular and cerebrovascular events.
1). 10 Controlled clinical trials have not shown significant benefits attributable to the administration of epoetins when haemoglobin concentration is increased beyond the level necessary to control symptoms of anaemia and to avoid blood transfusion.
Supplementary iron therapy is recommended for all patients with serum ferritin values below 100 mcg/L or whose transferrin saturation is below 20%. Serum potassium levels should be monitored regularly during Aranesp therapy. Potassium elevation has been reported in a few patients receiving Aranesp, though causality has not been established.
If an elevated or rising potassium level is observed then consideration […]