2010/06/05

EPOETIN ALFA

Pharmacological action

Human recombinant erythropoietin, is a purified glycoprotein. Stimulates erythropoiesis. Synthesized in mammalian cells, which incorporated the gene encoding human erythropoietin. Biological and immunological properties identical to human erythropoietin isolated from the urine. The synthesis of endogenous erythropoietin by the kidneys and depends on the level of blood oxygenation.


Pharmacokinetics

After sc administration the concentration of the active substance in the plasma increased slowly, reaching a maximum level in 12-18 hours

After multiple in / at the introduction of T 1 / 2 in adult healthy patients is 4 h, in patients with renal failure - about 6 h in children - about 6 hours


Statement

Treatment of anemia associated with chronic renal failure in adult patients on hemo-or peritoneal dialysis, or who have shown dialysis, children who are on hemodialysis.

Treatment of anemia in cancer patients (receiving or not receiving chemotherapy) when nemieloidnyh tumors.

Prevention of anemia in cancer patients with tumors nemieloidnymi receiving long-course chemotherapy.

Treatment of anemia in HIV-infected patients receiving treatment with zidovudine, (at the level of endogenous erythropoietin ≤ 500 IU / ml).

In predepozitnoy programs before extensive surgery in patients with hematocrit levels of 33-39%, to facilitate the collection of autologous blood and reduce the risks associated with the use of allogeneic blood transfusions (when the expected demand for transfused blood is higher than the amount that can be obtained without the use of epoetin alpha).

Before carrying out an extensive operation with the expected high blood loss (2-4 units or 900-1800 ml) in adult patients with mild or moderate anemia (hemoglobin> 10 and ≤ 13 g / dl) to reduce the need for allogeneic blood transfusions and improve the recovery of erythropoiesis.


Dosage regimen

Enter n / a or / in. A single dose of 30-100 IU / kg, frequency and duration of administration set individually.


Side effect

Flu-like syndrome: possible dizziness, drowsiness, pyrexia, headache, pain in joints and muscles (mostly in the beginning of treatment).

Since the cardiovascular system: a dose-dependent increase in blood pressure, degradation of the flow of arterial hypertension (more often in patients with chronic renal failure) in some cases - hypertensive crises, malignant hypertension with symptoms of encephalopathy (headache, confusion) and generalized tonic -clonic convulsions.

On the part of the hemopoietic system: rarely - thrombocytosis.

From the coagulation system: in some cases - shunt thrombosis (in patients on hemodialysis with a tendency to hypotension or in the presence of stenoses, aneurysms).

On the part of the urinary system: hyperkalemia, hyperphosphatemia, increased concentrations of urea, creatinine, uric acid in blood plasma (in patients with chronic renal failure).

Allergic reactions: in some cases - mild to moderate skin rashes, eczema, urticaria, pruritus, angioedema.

Local reactions: possible redness, burning sensation, weak or moderate pain at the injection site (usually arise at n / a introduction).

Other: rarely - a potentially serious complications associated with respiratory failure or with a reduction in blood pressure, immune response (has minimal ability to induce formation of antibodies).


Contraindications

Uncontrolled hypertension, hypersensitivity to epoetin alfa.

Before the extensive surgery is not within predepozitnoy program using autologous blood is contraindicated in severe vascular disease (including coronary, carotid, cerebral, peripheral) and in recent myocardial infarction or acute ischemic stroke.


Application of pregnancy and breastfeeding

Safety of epoetin alfa during pregnancy and lactation not established.


Cautions

With caution used in patients with convulsive reactions in history; patients with increased risk of thrombosis or other vascular complications requires careful medical supervision.

Precautions used to treat gout.

Prior to the application should ensure that patients with hypertension were receiving antihypertensive therapy effectiveness.

Against the background of the application necessary to control blood pressure, paying attention to the emergence or strengthening of unusual headaches. This may require adjustment of the therapy or the appointment of antihypertensive agents. If despite adequate therapy of AD is not reduced, epoetin alfa should be abolished.

Prior to the use of epoetin alfa should assess the state of iron stores in the body. The majority of patients with chronic renal failure in cancer and HIV-infected patients, the level of ferritin in blood plasma decreases simultaneously with an increase in hematocrit. The level of ferritin should be determined during the entire course of treatment. If it is less than 100 ng / ml, we recommend replacement therapy with iron. Patients handing over of autologous blood and are in pre-or postoperative period, should also receive an additional adequate amount of iron.

During the period of application should monitor the level of hemoglobin, at least 1 time per week to achieve a stable level, then less frequently. In the pre-and postoperative hemoglobin levels should be checked more frequently if the initial level of less than 14 g / dl. It should also regularly monitor the level of hematocrit. During the first 8 weeks of therapy should regularly monitor the number of platelets, because epoetin alfa may cause moderate dose-dependent increase in the number of platelets, independently coming to the norm during the course of therapy, thrombocytosis is rare.

Note that the preoperative increase of hemoglobin levels may serve as a predisposing factor to the development of thrombotic complications. Before the planned surgery patients should receive adequate preventive antithrombotic therapy.

In the pre-and postoperative period is not recommended epoetin alfa at an initial level of hemoglobin more than 15 g / dl.

With caution to patients with porphyria. In chronic renal failure during therapy with epoetin alfa may be worsening porphyria.

Correction of anemia may be accompanied by improved appetite and increased intake of potassium and proteins. It should be borne in mind the possible need for periodic adjustment of parameters of dialysis to maintain the level of urea, creatinine and potassium within normal limits. Patients with chronic renal failure should be monitored levels of electrolytes in the blood serum.

Patients who are on hemodialysis, during therapy with epoetin alfa is often required increased doses of heparin during dialysis due to the increased hematocrit. If an inadequate dose of heparin can occlude dialysis system.

Patients with chronic renal failure and clinically manifested coronary heart disease or congestive heart failure supports the hemoglobin concentration should not exceed the recommended upper limit of the optimal concentration (no more than 10-12 g / dl in adults).

In the application in patients with impaired liver function may slow the biotransformation epoetin alfa and expressed increased erythropoiesis. Safety of epoetin alfa in this patient is not installed.

We can not completely exclude the possibility of influence of epoetin alfa on the growth of certain types of tumors, especially malignant tumors of the bone marrow.

It should comply with all the special warnings and precautions associated with autologous blood collection program (this applies to all patients receiving epoetin alfa).

Therapeutic effectiveness of epoetin alfa may reduce iron deficiency, folic acid, vitamin B 12, aluminum toxicity, intercurrent disease, occult bleeding, hemolysis, bone marrow fibrosis.

In experimental studies on animals in the study of chronic toxicity of epoetin alfa in some cases observed subclinical fibrosis of tissues of the bone marrow, and anemia with symptoms or without symptoms of bone marrow hypoplasia. It is believed that this is associated with the appearance of antibodies to epoetin alfa.

Mutagenic effect was not revealed.

Effects on ability to drive vehicles and management mechanisms

When using epoetin alfa to establish the optimal maintenance dose for patients with chronic renal failure should avoid occupations potentially hazardous activity due to increased risk of hypertension at the beginning of therapy.


Drug Interactions

Effects of epoetin alfa may increase while the introduction of blood products.

With simultaneous use of epoetin alfa with cyclosporine may decrease the plasma concentrations of the latter due to increases in the degree of its binding to red cells (in the application of this combination is necessary to monitor the concentration of cyclosporine in plasma and if necessary increase the dose).

Epoetin alfa should not be mixed with solutions of other drugs.