Erythropoietin (EPO)

Erythropoietin (EPO) is a naturally occurring protein hormone produced by specialized cells in the kidneys. These cells are sensitive to the by red blood cells, too few red blood cells (anemia) will result in erythropoietin release. Nowadays, all EPO on the market id Recombinant human erythropoietin (rHuEPO). There are five erythropoiesis-stimulating agents currently available; epoetin-alpha, epoetin-beta, epoetin-omega, epoetin-delta, and darbepoetin-alpha.

SPORT usage

A common practice that may be used by performance sportsmen (runners, cyclists, swimmers etc.) in an attempt to increase performance is Erythropoietin. This substance is produced naturally in the body by the kidneys and is used to regulate red blood cell production. Patients suffering from anemia or chronic renal failure are legally allowed to use this form medically, however some athletes have decided to take advantage of this substance as well.

Due to medical advances, we can now inject EPO rather than blood doping, which was the common method in the past. EPO works by increasing the bloods ability to carry oxygen, thus serving as an ergogenic aid. Some studies have shown that athletes have had an 9% increase in VO2 max, 7% increase in power output, and a 5% decrease in max heart rate ((Juhn, M., 2003).

While the benefits of using erythropoeitin are unquestionable, there are serious side affects that an athlete needs to consider. After injection, the blood has a higher concentration of red blood cells and a thicker viscosity. This may lead to thromboembolic events that could be fatal. I.e. if you dope more than necessary, thrombs may stop the bloodstream during the exercises and sportsmen dies. There are serious suspicios agains EPO for the deaths of some top cyclists during 80s and 90s.

Seizures and hypertension are also demonstrated in those athletes who are blood doping. Most athletic federations have banned this practice and a haemoglobin limit of 18.5 g/dL has been implemented.

The injection of EPO in the body is a practice that would be very beneficial to any athletes involved in endurance activities. It would allow them to carry more oxygen per unit of blood than before thus improving their performance. This is not a sound technique however as there are strict regulations around it and there are many adverse health consequences that have been reported.

Does EPO contain blood fractions?

While erythropoietin itself is not a blood product, some brands of the synthetic form do have a very small amount of a blood fraction added to them. The epoetin-alfa formulation (Epogen®, Procrit®) contains 2.5 mg human serum albumin. The albumin first prevents the pharmaceutical from sticking to the vial, and then acts as a carrier molecule to help the EPO remain in the bloodstream until it reaches its destination at the bone marrow.

Pharmacology


Stimulates RBC production.

Pharmacokinetics
Absorption

T max is 5 to 24 h (subcutaneous).

Elimination

Elimination half-life is approximately 4 to 13 h (IV).

Special Populations
Elderly

Pharmacokinetic data indicate no apparent difference in half-life among adult patients older or younger than 65 yr of age.
Children

Pharmacokinetic profile in children and adolescents is similar to that of adults. Limited data are available for neonates.

Indications and Usage

Treatment of anemia related to chronic renal failure (CRF), anemia related to zidovudine therapy in HIV-infected patients, and anemia due to chemotherapy in patients with metastatic nonmyeloid malignancies; reduction of allogeneic blood transfusions in surgery patients.
Unlabeled Uses

Anemia associated with critically ill patients, CHF, chronic disease (eg, rheumatoid arthritis), postpartum anemia, sickle cell disease, thalassemia, multiple myeloma, Jehovah's witnesses, radiation treatment, epidermolysis bullosa, porphyria, for athletic enhancement, sexual dysfunction, transfusional iron overload, uremic pruritus.
Contraindications

Hypersensitivity to mammalian cell–derived products or human albumin; uncontrolled hypertension.

Dosage and Administration
Cancer Patients
Adults

Subcutaneous 3 times/wk dosing: 150 units/kg 3 times/wk. Reduce the dose by 25% when Hgb reaches a level needed to avoid transfusion or increases more than 1 g/dL in any 2-wk period. Withhold the dose when Hgb exceeds a level needed to avoid transfusion and restart at 25% below the previous dose when the Hgb approaches a level where transfusions may be required. Increase the dosage to 300 units/kg 3 times/wk if the response is not satisfactory after 4 wk to achieve and maintain the lowest Hgb levels sufficient to avoid the need for RBC transfusion and not to exceed the upper safety limit of 12 g/dL. Discontinue if after 8 wk there is no response as measured by Hgb levels or if transfusions are still required. Weekly dosing: 40,000 units/wk. Reduce the dose by 25% when the Hgb reaches a level needed to avoid transfusion or increases more than 1 g/dL in any 2-wk period. Withhold the dose if the Hgb exceeds a level needed to avoid transfusion and restart at 25% below the previous dose when the Hgb approaches a level where transfusion may be required. Increase the dosage to 60,000 units/wk if the response is not satisfactory (no increase in Hgb by at least 1 g/dL after 4 wk of therapy, in the absence of an RBC transfusion) to achieve and maintain the lowest Hgb levels sufficient to avoid the need for RBC transfusion and not to exceed the upper safety limit of 12 g/dL. Discontinue if after 8 wk there is no response as measured by Hgb levels or if transfusions are still required.
Children

IV Weekly dosing: 600 units/kg/wk (max, 40,000 units/wk). Reduce the dose by 25% when the Hgb reaches a level needed to avoid transfusion or increases more than 1 g/dL in any 2-wk period. Withhold the dose if the Hgb exceeds a level needed to avoid transfusion and restart at 25% below the previous dose when the Hgb approaches a level where transfusion may be required. Increase the dosage to 900 units/kg/wk (max, 60,000 units/wk) if the response is not satisfactory (no increase in Hgb by at least 1 g/dL after 4 wk of therapy, in the absence of a RBC transfusion) to achieve and maintain the lowest Hgb levels sufficient to avoid the need for RBC transfusion and not to exceed the upper safety limit of 12 g/dL. Discontinue if after 8 wk there is no response as measured by Hgb levels or if transfusions are still required.
CRF
Adults

IV / Subcutaneous Individually titrate to achieve and maintain Hgb levels between 10 and 12 g/dL. Increases in dose should not be made more often than once monthly. Start with 50 to 100 units/kg 3 times/wk. Increase the dose by 25% if the Hgb is less than 10 g/dL and has not increased by 1 g/dL after 4 wk of therapy or if the Hgb decreases below 10 g/dL. Reduce the dose by 25% when the Hgb approaches 12 g/dL or the Hgb increases by more then 1 g/dL in any 2-wk period. If the Hgb continues to increase, temporarily withhold the dose until the Hgb begins to decrease, then reinitiate treatment at a dose approximately 25% below the previous dose.
Children

IV / Subcutaneous Individually titrate to achieve and maintain Hgb levels between 10 and 12 g/dL. Increases in dose should not be made more often than once monthly. Start with 50 units/kg 3 times/wk. Increase the dose by 25% if the Hgb is less than 10 g/dL and has not increased by 1 g/dL after 4 wk of therapy or if the Hgb decreases below 10 g/dL. Reduce the dose by 25% if Hgb approaches 12 g/dL or the Hgb increases by more then 1 g/dL in any 2-wk period. If the Hgb continues to increase, temporarily withhold the dose until the Hgb begins to decrease, then reinitiate treatment at a dose approximately 25% below the previous dose.
Surgery
Adults

Subcutaneous Prior to starting treatment, obtain Hgb to establish that it is more than 10 to less than 13 g/dL.
Usual dosage

300 units/kg/day for 10 days before surgery, on the day of surgery, and for 4 days after surgery.
Alternative dose schedule

Subcutaneous 600 units/kg in once-weekly doses (21, 14, and 7 days before surgery), plus a fourth dose on the day of surgery.
Zidovudine-Treated, HIV-Infected Patients
Adults

IV / Subcutaneous Prior to starting therapy, determine the endogenous serum erythropoietin level. Evidence suggests that patients receiving zidovudine with endogenous serum erythropoietin levels more than 500 milliunits/mL are unlikely to respond to epoetin alfa therapy. Titrate the epoetin alfa dosage to achieve and maintain the lowest Hgb level sufficient to avoid the need for blood transfusion and not to exceed the upper safety limit of 12 g/dL. For patients with serum erythropoietin levels of 500 milliunits/mL or less who are receiving zidovudine 4,200 mg/wk or less, the recommended starting dosage is epoetin alfa 100 units/kg 3 times/wk for 8 wk. Monitor the Hgb weekly. If the response is not satisfactory in terms of reducing transfusion requirement or increasing Hgb after 8 wk of therapy, the dosage of epoetin alfa can be increased by 50 to 100 units/kg 3 times/wk. Thereafter, evaluate the response every 4 to 8 wk and adjust the dose accordingly, in 50 to 100 units/kg increments 3 times/wk, to a dosage of epoetin alfa 300 units/kg 3 times/wk. After attaining the desired response, titrate the epoetin alfa dose to maintain the response. If the Hgb exceeds the upper safety limit of 12 g/dL, stop until the Hgb drops below 11 g/dL. Reduce by 25% when treatment is resumed and titrated to maintain the desired Hgb.

General Advice

For subcutaneous or IV bolus administration only. Not for intradermal, IM, or intra-arterial administration. IV route recommended for patients on hemodialysis.
Do not shake or vigorously agitate vial. Prolonged vigorous shaking may denature the glycoprotein, rendering it biologically inactive.
Do not administer if particulate matter, cloudiness, or discoloration is noted.
If transferrin saturation is less than 20%, give supplemental iron.
IV dose may be administered into venous line at end of dialysis procedure to obviate need for additional venous access.
Rotate subcutaneous injection sites.
Single-dose vials contain no preservative. Use only 1 dose/vial. Do not reenter vial. Discard any unused portion. Do not combine unused portions or save unused portions for later use.
Do not administer in conjunction with other drug solutions. However, at time of subcutaneous administration, single-use vials may be admixed in a syringe with bacteriostatic sodium chloride 0.9% with benzyl alcohol 0.9% at a 1:1 ratio. Multidose vials contain benzyl alcohol and admixing is not necessary.
Adjust dose to achieve and maintain lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL.
Storage/Stability

Store vials in refrigerator (36° to 46°F). Do not freeze or shake. Protect from light. Multidose vials may be stored in refrigerator at 36° to 46°F for up to 21 days after initial entry.