Veys N, Dhondt A, Lameire N
Pain at the injection site of subcutaneously administered
EPO: new EPO-alpha compared to original EPO-alpha and EPO-beta
43rd Annual ASAIO Conference, Atlanta
ASAIO J
(Apr) 43:72 1997
Pain on injection of subcutaneous erythropoietin (SC EPO) is an important
issue to many
dialysis patients, the importance of which may not be fully appreciated by
dialysis
providers. One approach to minimize pain is to use a highly concentrated EPO
solution and
minimize the injection volume. Veys et al studied three forms of EPO: two
forms of EPO-
alpha, one buffered with citrate and one with phosphate, and one form of EPO-
beta (not
available in the US). The concentration used was 2,000 U in 0.5 ml.
Patients received 4 injections "simultaneously"; the 3 EPO preparations and a
saline
control, and pain was assessed using a verpal scale and a visual analogue
scoring system.
Pain with the EPO-beta preparation was indistinguishable from that due to
injection of
the saline control, whereas pain was greater with the two EPO-alpha
preparations. Among
the latter, the citrate-buffered preparation was more painful than the
phosphate-buffered
compound.
Comment: This is an important abstract, the utility of which is lost
to US
nephrologists, where the only compounds available contain citrate-buffered
EPO-alpha along
with albumin. Use of a high concentration solution with reduced volume is
the only
solution available to US nephrologists to minimize pain during EPO injection,
and this
seems to work quite well.
(John T. Daugirdas, M.D., University of Illinois at Chicago)
Because the reviewer was unfamiliar with epoietin-beta, the question was put
out
on NEPHROL, for help from European nephrologists, re: what is the difference
between epoietin alpha vs. beta, and why should one cause less pain the the
other. The following response from Dr. Quentin Meulders is reproduced with
his permission:
Quentin Meulders, M.D., (Department of Nephrology, CH Henri Duffaut,
Avignon, France)
EPO-beta is synthesized by ovarian cells of Chinese hamster, but I don't
remember the details. Its physiological properties are exactly the same
as those of EPO-alpha. The difference is the excipient; until one year ago,
EPO-alpha contained ago human albumin, Na citrate and
citric acid (solution ready for injection) whereas EPO-beta
contains urea, NaCl, polysorbate 20 and some aminoacids (powder to be
diluted).
The clinical difference between the original EPO-alpha and beta was evident
to
everybody: Epo-beta is quite painless whereas EPO-alfa-induced pain was
sometimes important, although quite variable between patients. Now
EPO-alpha is available without citrate (but still with human
albumin), only for EPO-alpha in ready-to-use syringes, and not the old
flasks.
My experience with one patient who experimented with various EPO preparations
with regard to their painfulness on injection was as follows:
three preparations were tested: 1. old EPO-alpha with citrate - 2. EPO-beta -
3. Epo-alpha
without citrate. There was no difference in pain between the two latter
formulations.
We didn't perform double crossover trials or the like, but really, there does
not
seem to be any important difference between alpha and beta now with regard to
pain on injection in my experience.
On the other hand, one explanation for the absence of pain with EPO-beta
could be the presence of polysorbate 20 or TWEEN 20 (used in order to
prevent attachment of EPO to the wall of the flask - also used in ELISA
or RIA for the same reasons), maybe by interaction with subcutaneous nerves?
But this has never been demonstrated to my knowledge.
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43rd Annual ASAIO Conference, Atlanta
CRF by problem area :
Anemia/Erythropoietin/Iron