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P A R T 8
Drugs acting on the cardiovascular system
Darbepoetin alfa is an erythropoietin-like protein
produced in Chinese hamster ovary cells with the use
of recombinant DNA technology. This drug gained
negative publicity after it was used by athletes to increase
their RBC count in the hope that it would give them
more endurance and strength. Many athletic govern-
ing bodies now screen for the presence of darbepoetin
among other banned drugs. This drug has the advantage
of once-weekly administration, compared with two to
three times a week administration for epoetin. Methoxy
polyethylene glycol-epoetin beta, the newest drug in this
class, has the advantage of dosing once every 2 weeks
or once a month. Both darbepoetin alfa and methoxy
polyethylene glycol-epoetin beta are approved to treat
anaemias associated with chronic renal failure, includ-
ing people receiving dialysis. Darbepoetin alfa is also
used for treatment of anaemia induced by cancer chemo-
therapy. (See also Table 49.1.)
Pharmacokinetics
All of these drugs can be given IV or by subcutaneous
injection. Epoetin alfa, which is like endogenous erythro-
poietin, is metabolised in the serum through the normal
process that the body uses to clear erythropoietin. It has
a slow onset and peaks in 5 to 24 hours, and its duration
of effect is usually 24 hours. It has a half-life of 4 to
13 hours and is excreted in the urine. Darbepoetin alfa
has a half-life of 21 hours after intravenous administra-
tion or 49 hours after subcutaneous administration. It
reaches peak effects in 14 hours (if given IV) or 34 hours
(subcutaneously). Duration of effects is 24 to 72 hours
and excretion is through the urine. Methoxy polyethyl-
ene glycol-epoetin beta has a half-life of 67 hours. It has
a slow onset and reaches peak effects in 48 to 72 hours.
It is also cleared in the serum and excreted in the urine.
It is not known whether epoetin alfa or methoxy poly
ethylene glycol-epoetin enters breast milk; however,
darbepoetin alfa does cross into breast milk.
Contraindications and cautions
All three of these drugs are contraindicated in the
presence of uncontrolled hypertension
because of the
risk of even further hypertension when RBC numbers
increase and the pressure within the vascular system
also increases
; with known hypersensitivity to any
component of the drug
to avoid hypersensitivity reac-
tions
; and with breastfeeding
because of the potential
for allergic-type reactions with the neonate.
There are
no adequate studies in pregnancy, and so use should be
limited to those situations in which the benefit to the
mother clearly outweighs the potential risk to the fetus.
Use caution when administering any of these drugs
to people with normal renal functioning and adequate
levels of erythropoietin
because of the rebound decrease
in erythropoietin that will occur
and when administer-
ing them to a person with anaemia and normal renal
function
because this can cause more severe anaemia
(see Figure 49.3).
TABLE 49.1
DRUGS IN FOCUS Erythropoiesis-stimulating agents
Drug name
Dosage/route
Usual indications
darbepoetin alfa (Aranesp)
0.45 mcg/kg IV or SC once per week;
2.25 mcg/kg per week SC (with
chemotherapy)
Treatment of anaemia associated with
chronic renal failure, including people
on dialysis; treatment of chemotherapy-
induced anaemia
epoetin alfa (Eprex)
50–100 units/kg IV or SC three times per
week; 300 units/kg per day SC for 15 days
(reduction of need for blood transfusions)
Treatment of anaemia associated with
renal failure and people on dialysis;
reduction in need for people undergoing
surgical procedures; treatment of
anaemia associated with AIDS therapy;
treatment of anaemia associated with
cancer chemotherapy
epoetin beta
(NeoRecormon)
60 units/kg SC or 120 units/kg/week x 3 doses
IV
Treatment of anaemia associated with
chronic renal failure, individuals with
non-myeloid malignancy, or to augment
autologous blood transfusion
epoetin lambda (Novicrit)
Elective surgery: 600 IU/kg SC weekly for
3 weeks; Autologous predonation program
300–600 IU/kg IV weekly for 3 weeks
Chronic renal failure: 75–300 IU/kg IV weekly
Treatment of anaemia associated with
chronic renal failure, individuals with
non-myeloid malignancy, or to augment
autologous blood transfusion
methoxy polyethylene
glycol-epoetin beta
(Mircera)
0.6 mcg/kg SC once every 2 weeks; when
desired haemoglobin level is reached,
1.2 mcg/kg SC once each month
Treatment of anaemia associated with
chronic renal failure, including people
undergoing dialysis treatment
