Epoetin alfa sold under brand name of Epofer 10000IU and which is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. RBCs (Red blood cells) are originated in the bone marrow (the spongy tissue inside the bone). To make red blood cells, the body regulate enough supply of erythropoietin (EPO), a hormone which is formed by the kidney. It helps to make red blood cells. When have more red blood cells increases the haemoglobin levels. Haemoglobin is the protein in red blood cells which is needed for blood carry oxygen throughout the body.
Anemia is a disorder which arise when there is not enough haemoglobin in a person's blood. There are different causes of anaemia. For instance, Anemia can be caused by the body's impotence to produce enough EPO to make red blood cells. In case, the person may have to undergo blood transfusion to cure this type of anaemia. If you have anaemia, your physician can determine the cause.
Epofer 10000IU injection is indicated for the treatment of following conditions
• Anemia due to chronic kidney disease including patients on dialysis or without dialysis to reduce the requirement of RBC transfusion
• Anemia due to Zidovudine given ≤ 4200 mg/week in HIV infection patients with levels of erythropoietin endogenous serum of ≤munits/mL.
• Anemia due to effect of concomitant myelosuppressive chemotherapy
• Epofer 10000IU is indicated to decrease the uses for allogeneic RBC transfusions among patients with perioperative haemoglobin > 10 to ≤ 13 g/dL who are at serious risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. Epofer 10000IU is not used for patients who are willing to donate autologous blood pre-operatively.
Mechanism of action
Erythropoietin controls erythropoiesis by stimulating the differentiation and replication of erythroid precursors, stimulating the release of reticulocytes into the circulation, and synthesis of cellular haemoglobin. Recombinant human erythropoietin is available as epoetin alfa and epoetin beta which are required in the management of anaemia’s along with CRF, cancer chemotherapy and anti-aids drug zidovudine.
Time to peak plasma concentration of Epofer 10000IU is 20 to 25 hours and bioavailability of SC injectable Epofer 10000IU is much lower than IV injection and is 20-24%.
Adult and paediatric with CRF peak plasma level is 5 to 24 hours
volume of distribution is range of 40-63.80 ml/kg and Epofer 10000IU has no plasma protein binding
bounding of erythropoietin and epoetin alfa to EPO-R causes to cellular internalization, which includes the degradation of the ligand.
Erythropoietin and epoetin alfa may also be disgraced by the reticuloendothelial scavenging pathway or lymphatic system
Epofer 10000IU injection are cleared through uptake and degradation via the EPO-R-expressing cells and may also involve other cellular
pathways in the interstitium. Only a little amount of unchanged epoetin alfa is found in the urine.
Half-life in adult is 4 hours and for children is approx. 6 hours
Adult and paediatric with CRF the half-life is 4 to 13 hours
Zidovudine-treated Patients with HIV-infection :
Starting Dose The prescribed initial dose in adults is 100 Units/kg as an IV or SC injection 3 times per week.
Discontinue Epofer if an increase in haemoglobin is not achieved at a dose of 300 Units/kg for 8 weeks.
Patients on Cancer Chemotherapy :
Start Epofer in patients on cancer chemotherapy only if the haemoglobin is less than 10 g/dL, and if there is a minimum of two additional months of planned chemotherapy.
Use the less dose of EPOFER needed to avoid RBC transfusions.
Usually Starting Dose:
For Adults administer the dose of 150 Units/kg subcutaneously 3 times per week until completion of a chemotherapy course or 40,000 Units subcutaneously weekly until completion of a chemotherapy course.
Paediatric Patients (5 to 18 years): 600 Units/kg intravenously weekly until completion of a chemotherapy course. Patients with Chronic Kidney Disease
For all patients with CKD:
When starting or adjusting therapy, monitor haemoglobin levels at least weekly until stable, then monitor at least monthly. Avoid rises of the dose more frequently than once every 4 weeks. Reduces in dose can occur more frequently. Avoid frequent dose adjustments.
If the haemoglobin increases rapidly, decrease the dose of Epofer by 25% or more as required to reduce fast responses.
For adult patients with CKD on dialysis:
• Start Epofer therapy when the haemoglobin level is less than 10 g/dL.
• If the haemoglobin level approaches or exceeds 11 g/dL, decrease the dose of Epofer.
• The usual starting dose for adult patients is 50 to 100 Units/kg 3 times weekly IV or SC. The intravenous route is prescribed for patients on haemodialysis.
For paediatric patients with CKD:
Start Epofer therapy only when the haemoglobin level is less than 10 g/dL.
If the haemoglobin level approaches or exceeds 12 g/dL, reduce or interrupt the dose of Epofer.
The usual starting dose for paediatric patients (ages 1 month or older) is 50 Units/kg 3 times weekly intravenously or subcutaneously.
Surgery Patients :
The prescribed Epofer injections are:
• 300 Units/kg per day subcutaneously (SC) for 15 days total: given daily for 10 days before surgery, on the day of surgery, and for 4 days after surgery.
• 600 Units/kg subcutaneously (SC) in 4 doses given the patients 21, 14, and 7 days before surgery and on the day of surgery.
Epofer 10000IU overdose can cause by above the desired level of haemoglobin levels, which must be controlled with discontinuation or reduction of Epofer 10000IU dosage with phlebotomy.
The injection Epofer 10000IU has some serious side effects like:
• Increase mortality, Myocardial infarction, stroke and thromboembolism
• Increased mortality/ risk of tumor progression or recurrence in patients.
• Serious allergic reactions
• Severe cutaneous reaction.
High incidence of death, myocardial infarction (MI), stroke, and thromboembolism: while Using ESAs to aim haemoglobin level of >11 g/dL rises risk of severe adverse cardiovascular reactions
Special caution usage in hypertension, iron deficiency, folate or B12 deficiency, congestive heart failure (CHF), coronary artery disease (CAD), seizure disorder, sickle-cell disease, haemolytic Anemia, porphyria, hematologic disorders
Cancer patients will Increased tumor development rate when dosed to achieve haemoglobin level of >12 mg/ld.
In Chronic renal failure patients at starting of treatment, transferrin saturation should be ≥20% and ferritin ≥100 ng/mL
Patients go through surgery are at high risk for DVT; concomitant DVT prophylaxis is strongly recommended In Zidovudine-treated patients may have response only when zidovudine dosage <4200 mg/wk. and endogenous epoetin <500 U/mL
In Dialysis patients having IV administration recommended to decrease red-cell aplasia risk; rises anticoagulation with heparin may be needed to prohibit clotting of extracorporeal circuit during haemodialysis
Avoid increase dose more frequently than once monthly.
Patients Contains albumin; may carry extremely specific risk for transmission or viral diseases or Creutzfeldt-Jakob disease.
In Cases of PRCA and of severe Anemia, with or without other cytopenia’s that appears following the growth of neutralizing antibodies to erythropoietin resulted in patients treated with epoetin alfa