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Apologies for cross-posting.
The surgeon at our hospital--during a consult with
an internist at another site--was told that a liter
of IV fluid had to be given with each dose of IV
erythromycin. He was given to understand by the
internist that erythromycin is poorly distributed
and taken up by target organs, and that it was
necessary to provide a large amount of fluid in order
to overcome this. He (of course) asked me if I knew
anything about this. Shuffling and smiling, I owned
that the only characteristic of this drug that I knew
of that has to do with fluid is to give it in enough
to prevent phlebitis. But a LITER?
I told him I'd look into it.
I've never heard of this (if I have the story straight).
If this is something old, commonplace, and well-known
then shame on me. Is there any truth to this?
I tried MEDLINE without success, and I couldn't find
anything through a Web search.
Any info out there?
***************************************
Randy Trinkle, BScPharm, BA
Pharmacy Department
Prince Rupert Regional Hospital
mailto:rtrinkle.at.mail.citytel.net
Health Science links:
http://www.rupert.net/~rtrinkle
***************************************
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[A few replies - db]
Date: Tue, 02 Feb 99 08:23:37 -0700
From: "Mike Jones"
To:
Subject: Re: Super-hydration with IV erythromycin
MIME-Version: 1.0
Randy,
I pulled the following from DrugDex(R), MICROMEDEX, Inc.
Hope this helps.
Mike Jones, Pharm.D.
INTRAVENOUS SOLUTION PREPARATION
=B7a. Prepare the initial solution of erythromycin (Ilotycin
Gluceptate(R)) by adding at least 20 milliliters of STERILE WATER FOR
INJECTION
to the 1-gram vial. Use only STERILE WATER FOR INJECTION without
preservatives.
Shake the vial to insure that all of the drug is dissolved. Refrigerate and
use
within 7 days (Prod Info Ilotycin Gluceptate(R), 1998).
=B7b. Reconstituted erythromycin (Ilotycin
Gluceptate(R)) may be added to 0.9% Sodium Chloride
Injection or 5% Dextrose in Water to provide 1
gram/liter. Intravenous fluid admixtures with a pH
below 5.5 may lose potency rapidly; therefore,
administer the solution within 4 hours after dilution
(Prod Info Ilotycin Gluceptate(R), 1998).
=B7c. If administering the intravenous (IV) admixture
over a prolonged period, it is suggested to buffer the
pH to neutrality. For IV antibiotic mixtures in 500 or
1000 milliliters of 5% Dextrose in Water, add 1
ampoule of full-strength Buff(TM)(Phosphate-Carbonate
Buffer, Travenol) or 5 milliliters of Neut(R)(Sodium
Bicarbonate 4% Additive Solution, Abbott). For the same
volume of 0.9% Sodium Chloride Injection, add 1 ampoule
of half-strength Buff(TM) or 5 mL Neut(R)(Prod Info
Ilotycin Gluceptate(R), 1998).
=B7d. If erythromycin is to be administered in 100 to 250 milliliters of
fluid by
a volume control set
(eg,etriset(R)(McGaw), Volu-Trole(R) "B"(Cutter), Soluset(R)(Abbott), or
Buretrol(R)(Baxter-Travenol) buffer the intravenous fluid in its primary
container prior to adding it to the
volumetric administration set (Prod Info Ilotycin Gluceptate(R), 1998).
---
From: "Lakritz, Jeffrey"
To: "'PharmPK.aaa.pharm.cpb.uokhsc.edu'"
Subject: Re: Super-hydration with IV erythromycin
Date: Tue, 2 Feb 1999 09:30:11 -0600
MIME-Version: 1.0
I was under the impression that you had to give it diluted in 1 liter as it
can produce adverse reactions when given in concentrated form. If I
remember correctly, the product insert (erythromycin lactobionate) indicates
that a 1 gram vial should be diluted in 1 liter of fluids and then given as
an IV infusion. Some crampiness, and shock like reactions are possible when
given as a bolus. Phlebitis is also a concern. These reactions are not
present in all individuals but are very concerning in those that do react.
Jeff Lakritz
University of Missouri-Columbia
---
From: elizabeth.migoya.-at-.pharma.Novartis.com
X-Lotus-FromDomain: PH.-at-.N1
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
Date: Tue, 2 Feb 1999 12:22:06 -0500
Subject: Re: Super-hydration with IV erythromycin
Mime-Version: 1.0
Look in Trissels Handbook for Injectable Drugs - I know that this is not
true, IV erythromycin is administered frequently to pediatric patients and
there is no way they could tolerate 1L of fluid.
Elizabeth M. Migoya, PharmD
Clinical Pharmacokineticist
Novartis Pharmaceuticals
---
From: "Anaizi, Nasr"
To: Multiple recipients of PharmPK - Sent by
, "'PharmPK.aaa.pharm.cpb.uokhsc.edu'"
Subject: Re: Super-hydration with IV erythromycin
Date: Tue, 2 Feb 1999 15:21:53 -0500
How much fluid you need depends on several factors. The nature of the
diluent you choose is important; normal saline (NS) is the preferred medium.
If you choose to use D5W add a little NaHCO3 to ensure a roughly neutral pH
(between 6.5 and 7.5). One gram of erythromycin lactobionate can be
dissolved in as little as 100 mL NS (+ 1 mEq of NaHCO3) and infused over 30
to 60 minutes. We normally use a volume of 250 mL NS (no NaHCO3 is
necessary) .
However, if the drug is to be administered by continuous infusion (say, one
gram over 6 hrs) the concentration should not exceed 2 mg/mL (one gram would
require at least 500 mL). This precaution is probably related to the
phlebitis you mentioned. Thus, you can use small volumes for intermittent
infusions and large volumes for constant infusion. The latter is
pharmacodynamically better and appears to be kinder to the endothelium.
You may find this information in the package insert or in Gahart's book on
intravenous medications.
Nasr H. Anaizi, PhD RPh
Clinical Pharmacy Specialist
Renal & Transplant Therapeutics
and Clinical Pharmacokinetics
Strong Health Pharmacy
University of Rochester Med Cntr
601 Elmwood Ave, Box 638
Rochester, NY 14642
Phone: (716) 275-1696
Fax: (716) 756-5582
---
Date: Wed, 3 Feb 1999 11:50:21 +1100
From: Laurent Rivory
Reply-To: lrivory.-a-.canc.rpa.cs.nsw.gov.au
Organization: Sydney Cancer Centre - CSAHS
X-Accept-Language: en
MIME-Version: 1.0
To: PharmPK.-at-.pharm.cpb.uokhsc.edu
Subject: Re: Super-hydration with IV erythromycin
The quantity of fluid required for IV erythromycin infusion is related
to the dose. It is recommended that the concentration of erythromycin
in the infusion not exceed 1 mg/ml for slow infusion. Higher
concentrations may lead to phlebitis and vessel pain. Therefore, 1
liter is not extravagant particularly for a dose of 1g.
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[Two more messages - db]
Date: Wed, 3 Feb 1999 02:04:21 -0700 (MST)
X-Sender: ml11439.aaa.pop.goodnet.com
Mime-Version: 1.0
To: PharmPK.-at-.pharm.cpb.uokhsc.edu
From: ml11439.-a-.goodnet.com (Michael J. Leibold)
Subject: Re: Super-hydration with IV erythromycin; Some factors
Hello,
Hospital pharmacies typically dilute erythromycin as follows:
eythromycn 500mg/100cc D5W with 1.0 cc neut (NaHCO3)
erythromycin 1000mg/250cc D5W with 2.5 cc neut (NaHCO3)
The dilution is to minimize venous irritation and phlebitis, while the
neut is added for stability(minimizing acid-catalyzed hydrolysis).
Further dilution could theoretically minimize venous irritation, while
its effects on pharmacokinetics might be reflected in volume of distribution.
It is cleared hepatically and transient increases in plasma volume would
probably not increase clearance. A Vd of 0.78 L/kg indicates that is
distributed
into more than just the ECF, and data indicates that erythromycin is
extensively distributed into tissue with the exception of the brain.
Factors which could influence the pharmacodynamics of erythromycin when
given
in large volume are: 1) an increased cardiac output which could possibly
enhance
tissue penetration, although this is a not a common intervention used to
increase antibiotic penetration; 2) an increase in the time that plasma
concentrations exceed the MIC of the infecting organism, and this is
well-known intervention used for beta-lactams, but tried usuccessfully for
aminoglycosides. Erthromycin is bacteriostatic and achieves a Cmax of
~10ug/ml after infusion. MIC's in the
area of 1ug/ml could be influenced by a continous infusion versus an
intermittent
infsion, since the T1/2 is about 1.6 hours and the typical dosage interval is
8 hours.
Mike Leibold, PharmD, RPh
ML11439.aaa.goodnet.com
---
Comments: Authenticated sender is
From: "Randy Trinkle"
To: PharmPK.at.pharm.cpb.uokhsc.edu
Date: Tue, 2 Feb 1999 18:38:03 -0700
MIME-Version: 1.0
Subject: re: erythromycin
Priority: normal
> However, if the drug is to be administered by continuous infusion
> (say, one gram over 6 hrs) the concentration should not exceed 2
> mg/mL (one gram would require at least 500 mL). This precaution is
> probably related to the phlebitis you mentioned. Thus, you can use
> small volumes for intermittent infusions and large volumes for
> constant infusion.
> The latter is **pharmacodynamically** better and
> appears to be kinder to the endothelium.
This last bit was really the gist of the question. Apart
from reducing risk of phlebitis, what is the 'pharmacodynamic'
benefit of a lower concentration if given by continuous
infusion? The surgeon was (putatively) told by the
internist that erythromycin is poorly taken up by target
organs unless given in/with a liter of fluid.
***************************************
Randy Trinkle, BScPharm, BA
Pharmacy Department
Prince Rupert Regional Hospital
mailto:rtrinkle.-at-.mail.citytel.net
Health Science links:
http://www.rupert.net/~rtrinkle
***************************************
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