EPOVAX Epoetin Alfa 4,000 IU / mL Solution for IV/SC Injection 1mL 10's

In the management of anemia of chronic renal failure; In adults receiving chemotherapy for non-myeloid malignant disease; In adult HIV-positive patient in zidovudine therapy; and to increase the yield of autologous blood.

 

Erythropoietin is a glycosylated protein hormone and a haematopoietic growth factor. It is secreted primarily by the kidneys, although a small amount is produced in extrarenal sites such as the liver. Erythropoietin regulates erythropoiesis by stimulating the differentiation and proliferation of erythroid precursors, the release of reticulocytes into the circulation, and the synthesis of cellular haemoglobin. The release of erythropoietin is promoted by hypoxia or anaemia, and up to 1000 times the normal serum-erythropoietin concentration may be reached under these conditions; this response may be impaired in some disease states such as chronic renal failure.
The haematological response to erythropoietin is reduced if there is an inadequate supply of iron. For an outline of blood cell formation in general and average cell counts in adults.
Epoetin alfa and epoetin beta are recombinant human erythropoietins available for clinical use that have the same pharmacological actions as endogenous erythropoietin. They are used in the management of anaemia associated with chronic renal failure in dialysis and predialysis patients; they may reduce or obviate the need or blood transfusions in these patients. Epoetin delta is under investigation for anaemia in chronic renal failure. Epoetin Alfa and epoetin beta are also used in the management of chemotherapy-induced anaemia in patients with non-myeloid malignant disease. Epoetin alfa is used in zidovudine-related anaemia in HIV-positive patients. Epoetin beta is used in the management of anaemia of prematurity. Recombinant human erythropoietin is also being evaluated in the management of other types of normocytic-normochromic anaemias, including that associated with inflammatory disorders such as rheumatoid arthritis. In all patients, iron status should be monitored and supplementation provided if necessary.
Epoetin alfa and epoetin beta may also be used in patients with moderate anaemia (but no iron deficiency) before elective surgery to increase the yield of blood collected for autologous blood transfusions. Epoetin alfa may also be used in such patients to reduce the need for allogenic blood transfusions.
In the management of anaemia of chronic renal failure epoetin alfa or epoetin beta may be given subcutaneously or intravenously, depending on the formulation. The intravenous route is recommended for patients on haemodialysis. The aim of treatment is to increase the haemoglobin concentration to 10 to 12 g per 100 mL or to increase the haematocrit to 30 to 36%. The rate of rise in haemoglobin should be gradual to minimise adverse effects such as hypertension, a rate not exceeding 2 g per 100 mL per month is suggested.
Epoetin alfa may be given by intravenous injection over at least 1 minute; slow intravenous injection over 5 minutes may be used in patients who experience flu-like symptoms as adverse effects. Epoetin alfa may also be given subcutaneously, but preparations that contain polysorbate 80 should only be given intravenously in this group of patients.
In predialysis and haemodialysis patients, a Recommended initial close epoetin alfa is 50 international units/kg three times weekly; a higher initial dose of 50 to 100 units/kg three times weekly has been suggested in the USA.
Doses may be increased at 4-week intervals in increment of 25 units/kg three times weekly until the target is reached.
In patients on peritoneal an initial dose of 50 units/kg given intravenously twice weekly may be used.
Once the target is reached doses may need to be adjusted, and even decreased, for maintenance therapy.
The usual total weekly maintenance dose of epoetin alfa in predialysis patients is 50 to 100 units/kg given in three divided doses, and in haemodialysis patients it is about 75 to 300 units/kg given in three divided doses. In predialysis patients a total weekly dose of 600 units/kg should not be exceeded. In patients on peritoneal dialysis, the usual total weekly maintenance dose is 50 to 100 units/kg given intravenously in two divided doses.
In children, epoetin alfa may be given intravenously to those on haemodialysis.
The initial dose is 50 units/kg three times weekly. The dose may be increase at 4-week intervals in increments of 25 units/kg three times weekly until a target haemoglobin concentration of 9.5 to 11 g per 100 mL is reached.
The total weekly maintenance dose given in three divided doses is: 225 to 450 units/kg for those weighing less than 10 kg; 180 to 450 units/kg for those weighing 10 to 30 kg; 90 to 300 units/kg for those weighing over 30 kg.
In patients with non-myeloid malignant disease receiving chemotherapy, epoetin alfa or epoetin beta may be given by subcutaneously injection in an initial dose of 150 units/kg three times weekly. The dose may be increased after 4 or 8 weeks, if necessary, to 300 units/kg three times weekly. If the response is still inadequate after 4 weeks at this higher dose, treatment should be stopped. As alternative regiments, the total weekly dose of epoetin beta may be given as a single dose or divided into 3 to 7 doses. Epoetin alfa may also be given in once-weekly doses of 450 units/kg or 40,000 units; the dose may be increased 60,000 units after 4 weeks if necessary. The rise in haemoglobin should be gradual; a rate not exceeding 2 g per 100 mL per month, and a target haemoglobin concentration of not more than 12 g per 100 mL, are suggested. After the end of chemotherapy, epoetin alfa or epoetin beta may be continued for up to one month.
In HIV-positive patients on zidovudine therapy, epoetin alfa may be beneficial if the endogenous serum-erythropoietin concentration is 500 milliunits/mL or Less. Epoetin alfa is given by subcutaneously or Intravenous injection in an initial dose of 100 units/kg three times weekly for 8 weeks. The dose may then be increased every 4 to 8 weeks by 50 to 100 units/kg three times weekly according to response. However, patients are unlikely to benefit from dose above 300 units/kg three times weekly if this dose has failed to elicit a satisfactory response.
To increase the yield of autologous blood, epoetin alfa or epoetin beta may be used with iron supplementation. The dose depends on the volume of blood required for collection and on factors such as the patients' whole blood volume and haematocrit. Suggested regimens are; epoetin alfa 600 units/kg given intravenously twice weekly starting 3 weeks before surgery up to 800 units/kg of epoetin beta intravenously, or up to 600 units/kg subcutaneously, twice weekly for 4 weeks before surgery.
To reduce the need for allogenic blood transfusion epoetin Alfa may be given in a dose of 600 units/kg subcutaneously once weekly starting 3 weeks before surgery, with a fourth dose given on the day of surgery, alternatively, when the time before surgery is short, 300 units/kg subcutaneously daily may be given for 10 days before surgery, on the day of surgery, and for 4 days after.
Administration in neonates: Recombinant human erythropoietin may be given to neonates for anaemia of prematurity. It is usually given by subcutaneous injection. Intravenous infusion in total parenteral nutrition solutions produced satisfactory results in a group of 20 neonates. Enteral dosage in one small study increased plasma-erythropoietin concentrations and peak reticulocyte counts, but in another larger study it had no effect.

 

Overdosage

Uncontrolled severe hypertension patients.
Patients' hypersensitive to the drug and other materials derived from mammalian cells, as well as human serum albumin.
It's suitable to control infections before use for patients with complicated infections.

Hematocrit should be checked periodically during treatment (once a week during the primary period, once every two weeks during maintenance phase) to avoid formation of excessive red cells (ensure which to be less than 36 vol %). Administration shall be discontinued provisionally, if excessive red cells are formed.
Diet shall be adjusted because application of this drug may cause slight elevation of serum potassium sometimes. Dosage shall be adjusted under the guidance of doctors if elevation of serum potassium occurs.
For patients with myocardial infarction, pulmonary infarction and cerebral infarction, and patients with allergic history and allergic tendency, use of the drug shall be careful.
During the treatment, demand of iron will increase because of effective hemopoiesis. Usually, the concentration of serum iron will decrease. Iron preparation shall be supplied everyday if serum ferritin is lower than 100 mg/mL or transferrin saturation is lower than 20%.
Deficiency of folic acid or vitamin B12 will lower curative effect of the drug, so does serious excessive aluminum.
Athlete shall use carefully.
Use in Children: No data to support the medication security for prematures, newborns and infants.
Use in Elderly: Elderly patients shall monitor blood pressure and hematocrit, and adjust dosage and frequency appropriately.

 

Use In Pregnancy & Lactation

Adverse Effects and Treatment: Adverse effects of epoetins include flu-like symptoms such as fever, chills, headache, arthralgias, myalgias, asthenia, dizziness, and tiredness, which occur especially at the start of treatment. Other effects include rashes, urticaria, nausea and vomiting, diarrhea, hyperkalaemia, and reactions at the injection site. Severe hypersensitivity reactions have been reported rarely. Pure red cell aplasia associated with neutralising antibodies has also been reported rarely in patients with chronic renal failure. Modest increases in the platelet count within the normal range may occur during epoetin therapy.
Hypertension is common with the use of epoetins, particularly in patients with renal failure, and is associated with a rapid rise in haematocrit. Hypertension crisis with encephalopathy and seizures has been reported, even in patients with initially normal or low blood pressure.
Reports of thromboembolism include myocardial ischaemia and infarction, transient ischaemic attacks and cerebrovascular accidents, deep-vein thrombosis, and pulmonary embolism. Shunt thromboses may occur in the arteriovenous fistulae of dialysis patients, and occlusion of the dialysis system is possible, due to an increased haematocrit.

Storage

Action

Haematopoietic Agents