Erythropoeitin Flashcards
What is erythropoeitin?
erythropoeitin alpha and beta are recombinant human erythropoeitins used to treat symptomatic anemia associated with erythropoietin deficiency in chronic renal failure and to increase the yield of autologous blood in normal individuals
What is the difference between erythropoeitin alpha and beta?
beta- is also used to prevent anaemia in preterm neonates of low birth weight. Only unpreserved formulations are to be used in neonates- other preparations may contain benzyl alcohol.
alpha- involved in the regulation of erythrocyte differentiation and maintenance of a physiological level of circulating erythrocyte mass
What is erythropoietin alpha indicated for?
alpha: symptomatic anemia assoc. with chronic renal failure in patients on hemodialysis
What is erythropoietin beta indicated for?
beta: symptomatic anemia assoc. with chronic renal failure
prophylaxis of anemia in preterm neonates of low birth weight
What is the dose of erythropoeitin alpha given?
by IV injection over 1-3 minutes.
Initially 50units/kg 3x weekly, adjusted according to response (in steps of 25units/kg 3x weekly) at intervals of at least 4 weeks.
Maintenace dose usually 25-100units/kg, 3x a week.
What is the dose of erythropoeitin beta given?
SC injection
initially 20units/kg 3x weekly for 4 weeks, increased in steps of 20units/kg 3x weekly.
NB: the total weekly dose may be divided into daily doses: maintenance dose, initially reduce dose by half, then adjust according to response at intervals of 1-2 weeks.
The total weekly maintenace dose may be given as a single dose OR in 3 or 7 dividied doses; MAXIMUM 720units/kg weekly.
What is the mechanism of action of erythropoeitin?
the recombinant erythropoietin binds to the erythropoietin receptor leading to receptor dimerisation. This facilitates activation of JAK-STAT signalling pathways within the cytosol.
The activated STAT (signal transducers and activators of transcription) proteins are translocated into the nucleus serving as transcription factors which regulate the activation of specific genes involved in cell division or differentiation.
What are the main PK and PD parameters of erythropoeitin?
PK: mean half life following IV administration was 4-6.1 hours in “normal” volunteers, and 6.5-9.3 hours in patients with chronic renal failure.
Mean half life following SC administration was 24 hours
10% excreted by kidneys.
What are the precautions associated with erythropoeitin use?
not approved for hepatitis C assoc. anemia
excludes vitamin B12, folic acid deficiency.
hypertension, ischaemic vascular disease, hypotension tendency, pregnancy, lactation, children
What are the contraindications associated with erythropoeitin use?
hypersensitivity to mammalian cell derived products, uncontrolled hypertension, previous erythropoietin assoc. pure red cell aplasia, surgery, severe coronary, peripheral arterial, carotid or cerebral vascular disease inclding recent MI or CVA.
patients who are unable to receive adequate antithrombotic prophylaxis or treatment.
What are the adverse reactions associated with erythropoeitin use?
common:
GI upset, arthralgia, flu like illness, rash, hypertension, thromboembolism
uncommon: thrombocythaemia, cerebral haemorrhage, seizuires
What are the drug interactions associated with erythropoeitin use?
no known clinically significant interactions, but effect of epoetin alpha may be potentiated by concomitant admin of a haematinic agent like ferrous sulfate when a deficiency state exists,
drugs which decrease erythropoiesis may decrease response to epoetin.
as cyclosporin is bound by RBCs, there is a potential drug interaction and blood levels of cyclosporin should be monitored.
What are the alarm bells associated with erythropoeitin use?
not approved for hepatitis C associated anemia, excluding vitamin B12, folic acid deficiency.
What monitoring is involved with erythropoeitin use?
electrolytes (CRF), platelets (1st 8 weeks), Fe status, Hb, BP, hepatic dysfunction
