Epogen (Epoetin Alfa); Pharmacological Management and Therapeutic Implications
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Epogen (Epoitin Alfa); Pharmacological Management and Therapeutic Implications

Abstract Anemia is the condition in which red blood cells (RBCs, also termed as erythrocytes) are not produced sufficiently to meet the need of normal body and thus not carrying sufficient amount of oxygen to the body tissues. Erythrocytes are abundantly produced in bone marrow by the process of erythropoesis, initiated by the hormone erythropoietin, found in kidney. Patients with renal failure are unable to produce enough erythropoietin to stimulate the erythropoesis process, resulting in lower production of erythrocytes (RBCs). Epogen (Epoetin alfa) is a special drug to stimulate the production of RBCs. This drug is made by the DNA recombinant technology with certain limitations and controlled dosage to the patients. In patients with Chronic Kidney Disease (CKD), HIV infected patients being treated by zidovudine and cancer patients being treated with chemotherapy, Epogen dosages are 50-100 units/kg thrice a week, 100 units/kg thrice a week and 600-900 units/kg thrice a week keeping an eye on hemoglobin level. Epoetin alfa (Epogen) injection is limited to use in certain conditions such as, if hemoglobin level rises to 11 g/dL ten Epogen is prohibited to administer. There are certain side effects of consuming Epogen ranging from local, gastrointestinal to dermatological.

Discussion Red Blood Cells (RBCs) are the essential part of human blood which carries oxygen to the body tissues. If there is lack of sufficient healthy RBCs in the body, the condition is called Anemia, ranging from mild to severe. Anemic patient mostly feel weak and tired. Anemia is of several types among which blood loss is the most common. Deficiency of Hemoglobin can also be the cause of anemia as it gives red color to RBCs and bonds with oxygen to distribute throughout the body. Third most common cause of anemia is the frequent destruction of RBCs. Epogen (epoetin alfa) is a prosthetic injection for the treatment of anemia in patients with chronic kidney diseases (CKD). Epoetin alfa is the type of erythropoietin which is a protein made by kidneys to order bone marrow to generate more RBCs if there is any deficiency. If this regular mechanism is defected and unable to generate enough RBCs then epoetin alfa in injected. This epoetin alfa is the result of recombinant DNA technology having chemical formula C815H1317N233O241S5. Patient has to consume epoetin alfa indefinitely as it doesn’t reverse the cause of anemia. HIV infected patients and cancer patients receiving chemotherapy and developed anemia also treated with epoetin alfa. Epoetin alfa is used to treat the patients with chronic renal failure who may or may not require dialysis. Patients don’t require dialysis; epoetin use should be limited depending upon the hematocrit values. HIV infected patients, being treated with zidovudine, are also treated with Epoetin for severe anemia in adults and children. Cancer patients receiving chemotherapy may also be given Epoetin if anemia occurred due to chemotherapy. Patients about to undergo nonvascular and noncardiac surgery are given epoetin for reducing the need of allergenic blood transfusions. It is highly recommended for the patients who are at high risk of blood loss during surgery. Epoetin alfa is formed by recombinant DNA technology with molecular weight of 30,400 Daltons comprising of 165 amino acids similar to that of erythropoietin (human erythropoietin). This artificially generated epoetin functions similarly to that of human erythropoietin by stimulating the process of erythropoesis in bone marrow which results in the formation of RBCs. Human erythropoietin is the hormone which stimulates bone marrow to produce adequate erythrocytes. This hormone is primarily found in kidney and anemia due to the chronic kidney disease (CKD) is occurred due to the deficiency of this hormone. Epoetin also monitored the slightly elevated levels of erythropoietin but not effective in patients with relatively high concentrations of erythropoietin.

Dosage

Epogen dosage is administered vigorously as it varies with patient’s condition. CKD (Chronic Kidney Disease) patients have higher risk of mortality if given to the hemoglobin level greater than 11 g/dL. Hemoglobin levels should be monitored weekly at first, then monthly if stable. While adjusting the dose, consider hemoglobin level. Frequent dosage adjustments shouldn’t be practiced. Lower the Epogen dose by 25% if hemoglobin rate rises rapidly. In non responsive patients Epogen dose can increase by 25% depending if hemoglobin rate is stable. If patient remains irresponsive for the period of 12 weeks upon continuous elevation of Epogen, use the lowest Epogen dose maintaining hemoglobin level to minimize the risk of RBC transfusion. If patient is on dialysis, initiate Epogen dosage with hemoglobin level less than 10 g/dL. Lower Epogen dose if hemoglobin level elevates up to 11 g/dL. For adults, recommended starting dose is 50-100 units/kg thrice a week and 50 units/kg thrice a week for pediatrics. For CKD patients not on dialysis, only consideration is to reduce the likelihood of RBC transfusion. Use the lowest dose of Epogen if hemoglobin level elevates up to 11 g/dL. Starting dose for HIV patients, treated with zidovudine is 100 units/kg thrice a week as intravenous/subcutaneous. Increase Epogen dose if hemoglobin level doesn’t elevate over a period of 8 weeks, by 50 to 100 units/kg for 4 – 8 weeks intervals until required hemoglobin level is reached to avoid RBC transfusion. If hemoglobin exceeds 12g/dL, stop Epogen therapy and resume only if hemoglobin level descends to less than 11 g/dL. In cancer patients on chemotherapy, Epogen use initiated only, when prescribed by oncologist. Initiate Epogen administration if hemoglobin level is less than 10 g/dL. Epogen therapy is initiated with minimum dosage which is 150 units/kg subcutaneously for thrice a week for adults and 600 units/kg intravenously for pediatric until the completion of chemotherapy course. This dosage can be reduced if hemoglobin increasing rate is higher than 1 g/dL in 2 week period, and if hemoglobin elevates up to the level to avoid RBC transfusion. Epogen dose can be increased if hemoglobin level remains under 10 g/dL. This dose can be raised up to 300 units/kg thrice a week in adults and 900 units/kg per week in children. If RBC transfusion still needed, discontinue Epogen. Epogen dosage in surgery patients is recommended as 300 units/kg daily subcutaneously for 15 days in total starting from 10 days before the surgery till 4 days afterwards, or 600 units/kg in 4 doses as 3, 2 and 1 week prior to the surgery and on the day of surgery.

Precautions

There are some precautions to be followed for the preparation and administration of Epogen. Don’t use either shaken or frozen Epogen. Vials shouldn’t be exposed to light. Discolored vials are never to be used in any case. Unused Epogen must be stored at 360F to 460F in multidose vials. After initial administration discard the remaining portion of Epogen. Shouldn’t use diluted Epogen and don’t mix with other drugs, prescribed otherwise.

Side Effeects

Epogen is highly tolerated in general but there are certain side effects of the drugs, ranging from immunological, oncologic to dermatologic, monitored depending upon the patients case history and cause of anemia. Immunologically erythropoietin neutralizes antibodies if patient is reported with pure red cell aplasia (PRCA) or anemia. Occasionally, flu is reported in 5% of the patients given Epogen intravenously in combination with low fever, myalgias, arthralgias and flank pain. These symptoms can be controlled by subcutaneous dosage or slower intravenous injection. Mostly dialysis patients complained about headache, nausea, vomiting, hypertension, tachycardia, shortness of breath and diarrhea. HIV Patients, treated zidovudine, were occasionally reported with edema and diarrhea as compared to the cancer patients on chemotherapy. Headache and seizures are the side effects affecting nervous system 15% and 5% respectively. In first three months of Epogen therapy, seizures occurred primarily due to hematocrit or blood pressure increase. Patients with seizures history are recommended to be monitored neurologically during the Epogen therapy. Dialysis patients may also experience hallucination during Epogen therapy. Cancerous side effects may occur in myeloid tumors’ patient due to Epogen growth factor, however, there isn’t significant data available to establish whether Epogen is having any adverse effect on tumor progression or not. Gastrointestinal side effects are also reported insignificantly, including nausea, vomiting and diarrhea, as compared to the CKD patients and patients infected with HIV. Cancer patients treating with chemotherapy have higher ration of diarrhea as compared to other. Epogen therapy may also cause mild skin rashes, urticaria and pain at injection site.
Conclusion
Epogen is the drug administered to regulate the production of erythrocytes, responsible for carrying oxygen to the body tissues. Anemic patients with Chronic kidney disease (CKD), HIV infected patients and Oncology patients have lower levels of erythropoietin in body causing decrease in production of RBCs. Epogen injection helps these patients to regularize the process of erythropoesis and stimulate RBCs production in bone marrow with certain limitation. Epogen administration should be monitored on regular basis and once patient is given Epogen, it is likely to be dependant of the drug indefinitely. Although this drug is quite effective and helpful in normalizing RBCs production but hemoglobin level monitoring is essential throughout the drug administration.

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