Darbepoetin Alfa

Registered South African indications:

• Anaemia

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Poorly controlled hypertension

Cautions

• Pregnancy
• Breastfeeding
• Latex hypersensitivity
• Malignancy
• Iron, folic acid or vitamin B12 deficiency
• Intercurrent infections
• Inflammatory or traumatic episodes
• Occult blood loss
• Haemolysis
• Severe aluminium toxicity
• Underlying haematologic diseases
• Bone marrow fibrosis
• Concomitant hepatitis C infection
• Sickle cell anaemia
• Epilepsy

Forms avail. in SA and covered in this monograph: inj

Symptomatic anaemia associated with chronic renal failure

Correction Phase:
Dialysis patients

• SC/IV: Initial: 0.45µg/kg, weekly; If haemoglobin increase is inadequate (<0.6mmol/l (1.0g/dl) in 4 weeks); Up-titrate by approx. 25% at intervals of 4 weeks according to response

Patients not on dialysis

• SC: Initial: 0.75μg/kg, every 2 weeks; If haemoglobin increase is inadequate (<0.6mmol/l in 4 weeks); Up-titrate by approx. 25% at intervals of 4 weeks according to response

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If the haemoglobin increases by >0.6mmol/l in a 2 week period; Dose should be decreased by 25%. If haemoglobin continues to increase, temporarily withhold treatment until haemoglobin begins to decrease; At this point re-initiate therapy at approx. 25% lower than the previous dose

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Maintenance phase:
Dialysis patients

• SC/IV: When converting from once weekly to every 2 weeks dosing; Start with double the previous once weekly dose

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In the maintenance phase, darbepoetin may continue to be administered as a single injection once weekly or once every two weeks

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Patients not on dialysis

• SC: When converting form every 2 weeks to once monthly dosing; Start with double the previous once every 2 weeks dose

All patients

• If dose adjustment required to maintain haemoglobin target; Up-titrate dose by approx. 25%
• If the rise in haemoglobin is 1.0g/dl in 2 weeks; Down-titrate by approx. 25%, depending on the haemoglobin increase
• If haemoglobin exceeds 12g/dl; Discontinue use until level falls below 12g/dl; Re-start therapy at approx. 25% below the previous dose

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 Haemoglobin target range of 10-12g/dl

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Patients should be monitored closely to ensure that the lowest approved dose of darbepoetin alfa is used to provide adequate control of the symptoms of anaemia

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After any dose or schedule adjustment, the haemoglobin should be monitored every 1-2 weeks. Dose changes in the maintenance phase of treatment should not be made more
frequently than every 2 weeks

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When changing the route of administration the same dose must be used and the
haemoglobin monitored every 1-2 weeks so that the appropriate dose adjustments
are made to keep the haemoglobin at the desired level

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SC use is preferable in patients who are not receiving haemodialysis to avoid the puncture of peripheral veins

Forms avail. in SA and covered in this monograph: inj

Symptomatic anaemia associated with chronic renal failure

Children <11 years

• Not established for use

Children ≥11years

• See adult dosage

Pregnancy

• Caution
• There are no adequate and well-controlled studies with darbepoetin alfa in pregnant women. Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. No alteration of fertility was detected. Caution should be exercised when prescribing darbepoetin alfa to pregnant women

Breastfeeding

• Caution; not recommended
• It is unknown whether darbepoetin alfa is excreted in human milk. A risk to the breastfeeding child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from darbepoetin alfa therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• No dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Stroke
• Seizures

Cardiovascular Disorders

• Hypertension
• Thromboembolic events

Skin and Subcutaneous Tissue Disorders

• Rash
• Erythema
• Injection site pain
• Blistering
• Skin exfoliation

Immune, Blood and Lymphatic System Disorders

• Pure red cell aplasia
• Hypersensitivity reactions

• Agents highly bound to red blood cells

• Haemoglobin  
• Serum iron  
• Fluid balance  
• Blood pressure  

Specific cases may require

• Folate levels
• Peripheral blood smear
• Vitamin B12 levels
• Reticulocyte count
• Renal function

Administration directions

• Before administration, the darbepoetin alfa solution should be inspected for visible particles. Only solutions which are colourless, clear or slightly opalescent should be injected
• Do not shake
• Allow the pre-filled syringe or pen to reach room temperature before injecting
• Rotate the injection sites and inject slowly to avoid discomfort at the site of injection
• In the absence of incompatibility studies, darbepoetin alfa should not be mixed or administered as an infusion with other medicinal products
• For single use only. Any unused product or waste material should be disposed of in accordance with local requirements

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 have three. The additional sugar residues are molecularly indistinct from those on the endogenous hormone. Despite these molecular changes, darbepoetin alfa retains a very narrow specificity for the erythropoietin receptor.

Injection 10μg/0.4ml

• Aranesp (Amgen) originator

Injection 20μg/0.5ml

• Aranesp (Amgen) originator

Injection 30μg/0.3ml

• Aranesp (Amgen) originator

Injection 40μg/0.4ml

• Aranesp (Amgen) originator

Injection 50μg/0.5ml

• Aranesp (Amgen) originator

Injection 60μg/0.3ml

• Aranesp (Amgen) originator

Injection 80μg/0.4ml

• Aranesp (Amgen) originator

Injection 100μg/0.5ml

• Aranesp (Amgen) originator

Injection 150μg/0.3ml

• Aranesp (Amgen) originator

Injection 300μg/0.6ml

• Aranesp (Amgen) originator