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wayovermyhead

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Oct 5 12 12:08 PM

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Methadone has been linked to cardiac arrhythmia.  (R)-methadone appears to confer a lower risk of QT
interval prolongation, resulting in debate over how best to treat patients needing this medication. A discussion of salient aspects of selecting therapy for opioid dependence and pain management and decision-making regarding methadone formulation follows.


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sapphire76

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#1 [url]

Oct 6 12 4:06 AM

I can't open the link for some reason @Way. Are they actually going to start prescribing Rmethadone for people with LQTS in the US??

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wayovermyhead

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#3 [url]

Oct 6 12 5:46 PM

Methadone has been linked to cardiac arrhythmia.
(R)-methadone appears to confer a lower risk of QT
interval prolongation, resulting in debate over how best
to treat patients needing this medication. A discussion of
salient aspects of selecting therapy for opioid dependence
and pain management and decision-making regarding
methadone formulation follows.
Since the groundbreaking work of Dole & Nyswander in
the 1960s [1], methadone has been a life-saving treatment
for heroin and, more recently, prescription opioid
analgesic addiction. Methadone is used increasingly as a
treatment for chronic pain, both malignant and nonmalignant
[2]. As methadone use has increased, associated
toxicities and overdose deaths have risen. Methadone
confers some risk for cardiac adverse events and sudden
death. Its use has been associated with arrhythmias, particularly
torsade de pointes [3]. This effect is mediated
through the ability of methadone to bind to human Etherà-
go-goRelatedGene (hERG) channels in cardiacmyocytes
[4], resulting in delayed repolarization.The risk is thought
to result mainly from the use of a racemic methadone
formulation that contains both (R)- and (S)-enantiomers.
The (R)-enantiomer is amu opioid agonist responsible for
therapeutic effects. The (S)-enantiomer is a poor mu
agonist and can block hERG channels to a greater degree
than the (R)-enantiomer,which has been postulated to be
responsible for cardiac adverse events in methadone use
[5]. This information, in the context of recent studies
showing a reduced effect of (R)- methadone on QTc interval
[6] has generated discussion of the consideration of
eliminating racemic methadone in favor of the exclusive
use of (R)-methadone or buprenorphine as a means of
resolving the cardiac safety issues related to current
methadone treatment. However, this is a multi-faceted
problem that deserves further consideration.
To address the cardiac safety issues with methadone
in the United States, the Substance Abuse and Mental
Health Services Administration (SAMHSA) convened a
panel of experts who made recommendations aimed at
enhancing safety for those needing chronic methadone
treatment. Recommendations included disclosure of
arrhythmia risk with methadone and obtaining a clinical
history of risk factors, including structural heart disease,
syncope and arrhythmia. Recommendations for monitoring
of cardiac QTc interval prior to and following methadone
therapy were included. Clinician attention to
potential drug interactions that might be associated with
delayed methadone clearance and higher plasma
concentrations was advised [3]. Concerns regarding
some recommendations were voiced within the
treatment community [7]. These included questions
about the interpretation of currently available data and
need for recommended interventions, concerns regarding
implementation barriers, the creation of undue
anxiety in patients and unnecessary evaluation procedures
and delaying or denying treatment to those
needing methadone. To date, SAMHSA has not adopted
these recommendations.
A proposed solution is the use of a formof methadone
that contains only the (R)-enantiomer. This methadone
formulation is available in the European Union and is in
widespread use in Germany. The use of a pure (R)-
formulation of methadone results in lower effective doses,
but its cost is up to 20% higher than the racemic formulation
(S. Walcher MD, personal communication).
Some in the United States have suggested that racemic
methadone be replaced by (R)-methadone. However, this
formulation of methadone is not US Food and Drug
Administration (FDA)-approved and, therefore, cannot be
prescribed in the United States. As a new drug, it is likely
that the FDA will require safety testing and clinical trials
to show its equivalence to the currently available racemic
mixture. Even if the FDA were to expedite the approval
process, substantial costs would be incurred by a pharmaceutical
manufacturer undertaking this drug development.
It is likely that this methadone formulation would
be significantly more expensive than currently available
methadone in the United States. Further, the use of (R)-
methadone would probably increase the cost of methadone
treatment in developing nations, for whom this
intervention is critically important and for whom higher
costs may result in either a reluctance to provide the
treatment or to expand the capacity of existing treatment
facilities.
It makes good clinical sense to evaluate each patient
and to determine an individualized treatment plan based
both on clinical need and patient choice. The question
then becomes who would benefit from racemic methadone
versus who needs the (R)-methadone formulation.
Any patient identified with pre-existing structural heart
disease or those receiving medications for co-occurring
disorders which may inhibit methadone metabolism
would benefit from (R)-methadone. Those without co-occurring medical or mental illness, in otherwise good health, with no evidence for prolongation of cardiac QT
interval, and receiving moderate doses of methadone
(less than 100 mg daily) would, in most cases, be able to
be maintained on the currently available and less expensive
racemic methadone formulation.
It is also important to consider alternative medication
treatments for those with opioid addiction. Buprenorphine
has less effect on QT interval at standard clinical
doses [8], but a recently approved transdermal formulation
has a ‘black box’ warning related to QT interval
lengthening with high doses [9]. Naltrexone, an opioid
antagonist medication which blocks the effects of an
ingested opioid, has been used far less widely in the treatment
of opioid dependence. While useful in motivated
populations such as health-care professionals [10], it has
had more limited success in less motivated groups [11].
However, it is now available as an oral formulation or as a
once-monthly injectable that might have better acceptability
with patients and, therefore, be associated with
greater adherence in those with opioid dependence.
As health-care reform progresses in the United States,
the integration of substance abuse, medical and mental
health services will be required. Current narcotic treatment
program services will, of necessity, need to evolve to
provide safer, more effective and integrated care. Methadone
is a drug that confers significant medical risk, and
the ability to assess that risk and provide the best treatment
for individual patients is essential. This tenet will
not be altered whether or not (R)-methadone is adopted
in the United States. However, the development of new
medications and the increasing options for those who
suffer with opioid dependence or who require chronic
methadone treatment to manage pain, as well as an
increasing understanding of how to manage the use of
these medications medically, can only benefit those
requiring these treatments. The clinical pharmacology of (R)-methadone appears to present important medical
advantages for some patients. Studies should be undertaken
in the United States to demonstrate its clinical efficacy
and safety relative to the racemic formulation of
methadone so that this medication can proceed to FDA
approval for clinical use. The availability of multiple
forms of methadone will permit clinicians to match treatments
to individual patient need resulting in improved
clinical outcomes.
Declaration of interests
None.
ELINORE F. MCCANCE-KATZ

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wayovermyhead

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sapphire76

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#4 [url]

Oct 7 12 4:11 AM

That's quite confusing. It says that SAMHSA convened a panel to discuss QT prolongation in MMT patients, and the panel recommended using Rmethadone for patients at risk, but SAMHSA didn't act on the recommendations.

Why the F did they bother convening a panel if they weren't going to listen to what it said?!!

Is single isomer methadone very much more expensive than racemic? If it was, it's not like they have to dose everyone with single isomer, just the "at risk" people.

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wayovermyhead

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#5 [url]

Oct 7 12 6:19 AM

I will tell you who to ask about it is whiterobot he has all the info on it....and yes SAMHSA often does this finds a key finding of fact but doesn't push it thru.....They use this kind of methadone out of the US in different countries and it works great.  Furthermore this type methadone would put an end to peak and troughs being questionable....methods of serum levels testing.

When my clinic told me I had qtc issues of course I used this as my best defense and it was given shrugs and very little conversation by my doctor.  Like oh well we can't do nothing about it...you may have to decrease your dose or move to suboxone (which I have failed at twice) etc....I would be so spittin mad.

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sapphire76

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#6 [url]

Oct 7 12 7:41 AM

We don't use it in the UK. Most of the methadone prescribed for addiction is done through the National Health Service, which is funded by the government, so I imagine cost is a huge consideration in what they do and don't prescibe.

Seems such a shame though that people with LQTS are being told to either suck it up and get on Suboxone, or to try abstinence.

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wayovermyhead

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#7 [url]

Oct 7 12 12:34 PM

I believe the same..especially since they are now sitting on the fence about is it such a big deal like it use to be.  MAKE IT NOT A BIG DEAL....I heard there is a slight cost increase like not even more than a dollar...I want to say something like 30 cents...

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wayovermyhead

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#8 [url]

Oct 7 12 12:35 PM

I am going to get wrobot involved he is the one with the most info regarding the racemic vs. non racemic...

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whiterobot122

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#9 [url]

Oct 7 12 2:05 PM

I have already spoke to Andrew Byrne about this issue and he believes it's mostly bologna. While he stated in severe cases it may make a difference, in most it would be no different, besides in terms of potency of methadone.

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sapphire76

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#11 [url]

Oct 8 12 5:32 AM

    I have already spoke to Andrew Byrne about this issue and he believes it's mostly bologna. While he stated in severe cases it may make a difference, in most it would be no different, besides in terms of potency of methadone.

-whiterobot122

So single insomer methadone will not help people with elevated QT's??? I am beyond confused.

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wayovermyhead

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#12 [url]

Oct 8 12 10:20 AM

I want to know this answer myself and Byrne would know.....

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wayovermyhead

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