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I have a therapuetic dilemma for which I can find no good
information.
Our hospital has begun using dalteparin both for DVT
prophylaxis following orthopod surgery and for the initial
treatment of an existing DVT. We have recently added enoxeparin to
trial for DVT prophylaxis following knee prosthesis surgery.
I am concerned about using a straightforward 100 U/kg (for
dalteparin) bid schedule for treatment of established DVT.
In an obese patient (and this has recently been a real case)
weight-based dosing results in a calculated dose that seems
very high to me. My concern involves the volume of distribution
of this drug. My thinking is that an obese patient would not have
a proportionately higher volume of distribution but a dose calculated
strictly by kilogram of real body weight would result in a huge
dose (in the case at hand 15000 units bid).
I cannot find *any* good info on the partition/distribution
of dalteparin or any other LMWH.
If someone is heavy and well-muscled then I would expect
a proportionately greater vascular volume, which is the
volume these agents appear to distribute to. However,
if someone's greater weight is due to lipid tissue, then I
would not, and a straightforward unit/kg dose would, I'm
afraid, result in dangerous overcoagulation.
I haven't gotten very useful info from the manufacturer,
just that the Vd is between 40-60 mL/kg. The range for
Vd that I've found in the literature for dalteparin is
3-11 L.
Bottom line--should dalteparin (and other LMWHs) be
dosed based on ideal/lean body mass?
Thanks.
********************************
Randy Trinkle, BScPharm, BA
Dept. of Pharmacy
Dawson Creek & District Hospital
Dawson Creek, BC
mailto: rtrinkle.aaa.pris.bc.ca
********************************
We're born wet, naked, and hungry.
After that things get worse.
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Randy
We have just performed a study at our hospital looking at the
pharmacokinetics of dalteparin in obese and normal weight individuals. The
study was undertaken by one of our pharmacists (Julie Yee) in conjunction
with myself. We are about to submit for publication, but here are a few
interim findings.
>I have a therapuetic dilemma for which I can find no good
>information.
So did we...
>I am concerned about using a straightforward 100 U/kg (for
>dalteparin) bid schedule for treatment of established DVT.
>In an obese patient (and this has recently been a real case)
>weight-based dosing results in a calculated dose that seems
>very high to me. My concern involves the volume of distribution
>of this drug. My thinking is that an obese patient would not have
>a proportionately higher volume of distribution but a dose calculated
>strictly by kilogram of real body weight would result in a huge
>dose (in the case at hand 15000 units bid).
Our recommendations for dosing dalteparin, prior to our study, appear
similar to yours (200 iu/kg sc once daily [DVT] or 120 iu/kg sc bid [massive
DVT or PE]). Given this an average patient, 70kg, would receive either
14000 iu or 16800 iu daily.
>
>I cannot find *any* good info on the partition/distribution
>of dalteparin or any other LMWH.
>
Neither could we.
>I haven't gotten very useful info from the manufacturer,
>just that the Vd is between 40-60 mL/kg. The range for
>Vd that I've found in the literature for dalteparin is
>3-11 L.
This is about what we found in the literature.
>
>Bottom line--should dalteparin (and other LMWHs) be
>dosed based on ideal/lean body mass?
>
The answer is not all that clear. To date we believe that the risk of
bleeding seems to be related to the peak concentration, and hence Vd would
be important. Some obese patients that we have treated with high doses (200
iu/kg/d) have had minor bleeding complications. However the trough is also
important to maintain clinical effect, and hence Cl is important. In our
study Vd correlated poorly with lean body weight {as determined by: LBW (kg)
= (height (cm) - 150 cm)*0.9 + 45 kg [+ 5 kg(Male)]} with an r2 of 0.05. Vd
correlated better with weight adjusted body weight r2=0.56 and total body
weight r2=0.52 (total body weight ranged from 55 to 155 kg). (Weight
adjusted body weight was determined as LBW + 40% of the difference of total
body weight and LBW.) Obviously given the moderate r2 not all obese
patients had large Vds and therefore there is some risk of bleeding when
obese individuals are dosed based on their total body weight.
We currently recommend either:
1. Dose on total body weight up to a patient weight of 90 kg. Heavier
patients are dosed as if they weighed 90kg (maxm dose/day is therefore
either 18000 iu or 21600 iu), or
2. Dose on weight adjusted body weight (this isn't popular with the house
staff!).
I hope this has been some help.
Regards
Steve
====================================================================Steve Duffull
Dept of Clinical Pharmacology
Christchurch Hospital
Private Bag 4710, CHCH
New Zealand
Ph +64 3 364 0900
Fax +64 3 364 0902
Email: sduffull.-at-.chmeds.ac.nz
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I would be extremely interested in the outcome of your quest. USA is still
behind
in the approval process of LMWH's for treatment however, I plan to use
LMWH's
for treatment as soon as approved and I'm sure this is a question which I
will have
to answer as well. Any tips about the use of enoxaparin for DVT treatment.
cmoney.-a-.nr.infi.net
----------
> From: Randy Trinkleby way of David_Bourne
> To: Multiple recipients of PharmPK - Sent by
> Subject: Adjusted weight-based dosing for LMWHs?
> Date: Monday, June 23, 1997 1:04 PM
>
> PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
> I have a therapuetic dilemma for which I can find no good
> information.
>
> Our hospital has begun using dalteparin both for DVT
> prophylaxis following orthopod surgery and for the initial
> treatment of an existing DVT. We have recently added enoxeparin to
> trial for DVT prophylaxis following knee prosthesis surgery.
>
> I am concerned about using a straightforward 100 U/kg (for
> dalteparin) bid schedule for treatment of established DVT.
> In an obese patient (and this has recently been a real case)
> weight-based dosing results in a calculated dose that seems
> very high to me. My concern involves the volume of distribution
> of this drug. My thinking is that an obese patient would not have
> a proportionately higher volume of distribution but a dose calculated
> strictly by kilogram of real body weight would result in a huge
> dose (in the case at hand 15000 units bid).
>
> I cannot find *any* good info on the partition/distribution
> of dalteparin or any other LMWH.
>
> If someone is heavy and well-muscled then I would expect
> a proportionately greater vascular volume, which is the
> volume these agents appear to distribute to. However,
> if someone's greater weight is due to lipid tissue, then I
> would not, and a straightforward unit/kg dose would, I'm
> afraid, result in dangerous overcoagulation.
>
> I haven't gotten very useful info from the manufacturer,
> just that the Vd is between 40-60 mL/kg. The range for
> Vd that I've found in the literature for dalteparin is
> 3-11 L.
>
> Bottom line--should dalteparin (and other LMWHs) be
> dosed based on ideal/lean body mass?
>
> Thanks.
> ********************************
> Randy Trinkle, BScPharm, BA
> Dept. of Pharmacy
> Dawson Creek & District Hospital
> Dawson Creek, BC
> mailto: rtrinkle.-at-.pris.bc.ca
> ********************************
>
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>Dr. Hirsch in Canada is the guru of heparin and lmwh therapy. I don't have
his address, but he is well known and published. Enoxaprin at 1mg/kg, twice
daily dosing is effective for DVT according to my sources, with Coumadin
starting on day 2, stop enoxaprin on day 5 or when coumadin is therapeutic.
This can be done by the patient or on an outpatient basis for a fraction of
the cost for hospitaliziation. There are a few caveats, but this is good
medicine. I imagine the new lmwh will be equally effective.
Back to the Top
> >Dr. Hirsch in Canada is the guru of heparin and lmwh therapy. I don't have
> his address, but he is well known and published. Enoxaprin at 1mg/kg, twice
> daily dosing is effective for DVT according to my sources, with Coumadin
> starting on day 2, stop enoxaprin on day 5 or when coumadin is therapeutic.
Why is Coumadin started on day 2?
Why not start ASAP?
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html
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Proteins C and S are both vitamin K-dependent anticoagulant
factors. Their half-lives are shorter than procoagulant factors,
hence the traditional overlap of 3-5 days of heparin and
warfarin.
Do LMWHs have a faster onset of global anticoagulation than
unfractionated heparin, in order to prevent warfarin-induced
necrosis secondary to the formation of micoremboli? If so,
what is the evidence?
********************************
Randy Trinkle, BScPharm, BA
Dept. of Pharmacy
Dawson Creek & District Hospital
Dawson Creek, BC
mailto://rtrinkle.aaa.pris.bc.ca
********************************
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)