Cytokines / Hematopoietic agents / Myeloid growth factors
Erythroid growth factors
Mechanisms of Action
- ERYTHROPOIETIN is the most important (but not sole) regulator of the proliferation of committed red blood cell progenitors
- interacts with erythropoietin receptors on red cell progenitors
- the erythropoietin receptor is a member of the JAK/STAT superfamily
- produced in the kidney
- inverse relationship between hematocrit (or hemoglobin) level and serum erythropoietin level
- exception is in chronic renal failure when erythropoietin levels are low because the kidneys cannot produce the growth factor
Pharmacokinetics
- ERYTHROPOIETIN (rHuEPO, epoetin alfa) is produced in response to severe anemia
- it has a relatively short half-life: given IV 3-4X per week
- DARBEPOETIN is a more heavily glycosylated form
- it has 2-3X longer half-life: given weekly
- METHOXY POLYETHYLENE GLYCOL EPOETIN has a covalently attached PEG polymer
- given IV or SC at 2-week or monthly intervals
Therapeutic Uses
- anemia
- secondary to chronic kidney disease (particularly effective)
- nearly all patients will require iron supplementation; some patients may require folate supplementation
- due to primary bone marrow disorders and secondary anemias
- secondary to chronic kidney disease (particularly effective)
- reduce the need for transfusion in high-risk surgical patients
- after phlebotomies for autologous transfusion
- iron overload (hemochromatosis)
- M-PEG-epoetin should not be used in patients with anemia due to cancer chemotherapy (clinical trial found significant increase in deaths)
- banned by the International Olympic Committee (increased red blood cell concentration may increase oxygen delivery to muscles and improve performance)
Side effects
LIFE-THREATENING: |
|
|
---|---|---|
SERIOUS | INNOCUOUS | |
COMMON |
|
|
RARE |
|