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Sotalol-warfarin
At our regional drug information service we got the following case. A
patient with arrhythmia started with sotalol while waiting for
electroconversion. The patient was already being treated with warfarin.
After few days the dose of warfarin had to be increased to three times (!!!)
the original dose in order to maintain the desired coagulation status. One
does not expect hepatic interactions since sotalol is not metabolised by
liver and the observed effect is too big to be explained by hemodynamic
changes only. We are still waiting for the 'dechallenge' effect. Is there a
pharmacokinetic explanation?
Kind regards
Erik Pomp
Regional Drug Information Centre
Bergen, Norway
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[Two replies - db]
Reply-To: "Stephen Duffull"
From: "Stephen Duffull"
To:
Subject: Re: PharmPK Sotalol-warfarin interaction??
Date: Wed, 3 Mar 1999 08:47:19 -0000
MIME-Version: 1.0
X-Priority: 3
Hi Erik
I can't help much but thought I might just add that drugs do
*not* have to be metabolised in order to interact with liver
enzymes and inhibit the metabolism of other drugs (take
cimetidine for example)...
Cheers
Steve
=====================
Stephen Duffull
School of Pharmacy
University of Manchester
Manchester, M13 9PL, UK
Ph +44 161 275 2355
Fax +44 161 275 2396
---
Date: Wed, 3 Mar 1999 11:56:52 -0800 (PST)
From: Stephen Day
Subject: Re: PharmPK Sotalol-warfarin interaction??
To: PharmPK.-a-.pharm.cpb.uokhsc.edu
MIME-Version: 1.0
One explanation could be that sotalol is causing cytochrome P450
enzyme induction in the liver. Two of the enzymes responsible for
warfarin metabolism, CYP1A2 and CYP2C19, are known to be induced by
some xenobiotics. Whether or not Sotalol is metabolized by by liver
would be inconsequential.
Stephen Day
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Dear Erik, An interesting case observation. Given the magnitude of dose
adjustment, I would have to say that it would appear that sotalol is either
inducing warfarin metabolism or effecting Vitamin K. Induction, if it
occurred, of the primary cytochrome P450 responsible for inactivating the
pahrmacologically active enantiomer of warfarin, CYP2C9 would be highly
usual. I have forwarded your request to Dr. William F. Trager of the
University of Washington in Seattle. Perhaps, Dr. Trager can assist you in
this interesting observation.
Tom Woolf
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