The concerns are the same for Actos as for Avandia.

The difference here is that Actos does not have a combination
Actos/metformin tablet available yet.

The increase in CHF risk has been well documented for both products, see
http://www.fda.gov/medwatch/SAFETY/2002/safety02.htm#thiazo .  The risk is
primarily in those treated with insulin at the same time.

When Actos has a similar combination drug, expect it to have very similar
warnings required by the FDA.

Metformin has a warning for use in congestive heart failure. Metformin
doesn’t increase the risk of heart failure, like Actos and Avandia. Rather,
the risk of lactic acidosis increases with heart failure.

That being said, the incidence of lactic acidosis, even in patients with
some degree of heart failure or renal disease, is very low. In fact, there
are now publications reporting how frequently metformin is used in patients
with heart, liver, or renal disease and the rarity of any problems from
lactic acidosis.

Cheers,
William C Biggs, MD

"JHA" <jad…@rossinilaw.com> wrote in message

news:10hn5iu5erjhled@corp.supernews.com…

- Hide quoted text — Show quoted text -

> Herman Rubin wrote:
>> In article <2nuttgF4keb…@uni-berlin.de>,
>> Peanutjake <peanutjak…@usa.com> wrote:

>>>FDA Safety Labeling Changes: August 4, 2004

>> The problems are NOT with metformin, but with glitazones.
>> Read the message carefully; the drug listed uses metformin
>> on in conjunction with one of these, and the problems exist with or
>> without metformin.

> Could you elaborate with respect to pioglitazone?  I don’t see any mention
> of it in the release.  Is there other evidence about pioglitazone, or is
> the idea just that they’re similar enough to have similar consequences?

- Hide quoted text — Show quoted text -

Herman Rubin wrote:
> In article <10hn5iu5erjh…@corp.supernews.com>,
> JHA  <jad…@rossinilaw.com> wrote:

>>Herman Rubin wrote:

>>>In article <2nuttgF4keb…@uni-berlin.de>,
>>>Peanutjake <peanutjak…@usa.com> wrote:

>>>>FDA Safety Labeling Changes: August 4, 2004

>>>The problems are NOT with metformin, but with glitazones.
>>>Read the message carefully; the drug listed uses metformin
>>>on in conjunction with one of these, and the problems
>>>exist with or without metformin.

>>Could you elaborate with respect to pioglitazone?  I don’t see any
>>mention of it in the release.  Is there other evidence about
>>pioglitazone, or is the idea just that they’re similar enough to have
>>similar consequences?

> They are similar.  They MIGHT be different enough that this
> problem does not arise, but I would be very suspicious.

–
"…in addition to being foreign territory the past is, as history, a
hall of mirrors that reflect the needs of souls observing from the present"
Glen Cook

>Yael Waknine

>Aug. 4, 2004 – The U.S. Food and Drug Administration (FDA) approved in May

revisions to drug safety
>labeling to advise healthcare professionals of the following changes: . .
.(snip). . .

>Rosiglitazone Maleate/Metformin HCl (Avandamet) Associated With Risk of

Cardiovascular Adverse
>Events

>On May 19, the FDA approved changes to the safety labeling for

rosiglitazone maleate/metformin HCl
>tablets (Avandamet, made by SB Pharmco), warning that thiazolidinediones

(alone or in combination
>with other antidiabetic agents) are associated with risk of fluid retention

that may exacerbate or

>lead to heart failure.. . . .

     Avandia,  Actos,  the TZD removed from the market,   and the TZDs in
clinical trials all offer the chance of an edema side-effect.  Avandia by
itself needs an edema warning.   Avandia with metformin needs an edema
warning

That’s why they are prescription-only items.  Somebody knowledgeable has to
monitor their performance to make certain that you are receiving the
striking benefits of the TZD class of meds but not suffering from excessive
side effect.

The best way to handle these situations is to read the package insert very
carefully so that you can pick up obvious side effects without waiting for
your next visit to the doc.
.

Regards
  Old Al

JHA  <jad…@rossinilaw.com> wrote:
>Herman Rubin wrote:
>> In article <2nuttgF4keb…@uni-berlin.de>,
>> Peanutjake <peanutjak…@usa.com> wrote:
>>>FDA Safety Labeling Changes: August 4, 2004
>> The problems are NOT with metformin, but with glitazones.
>> Read the message carefully; the drug listed uses metformin
>> on in conjunction with one of these, and the problems
>> exist with or without metformin.
>Could you elaborate with respect to pioglitazone?  I don’t see any
>mention of it in the release.  Is there other evidence about
>pioglitazone, or is the idea just that they’re similar enough to have
>similar consequences?

They are similar.  They MIGHT be different enough that this
problem does not arise, but I would be very suspicious.
—
This address is for information only.  I do not claim that these views
are those of the Statistics Department or of Purdue University.
Herman Rubin, Department of Statistics, Purdue University
hru…@stat.purdue.edu         Phone: (765)494-6054   FAX: (765)494-0558

Peanutjake <peanutjak…@usa.com> wrote:
>FDA Safety Labeling Changes: August 4, 2004

The problems are NOT with metformin, but with glitazones.
Read the message carefully; the drug listed uses metformin
on in conjunction with one of these, and the problems
exist with or without metformin.
—
This address is for information only.  I do not claim that these views
are those of the Statistics Department or of Purdue University.
Herman Rubin, Department of Statistics, Purdue University
hru…@stat.purdue.edu         Phone: (765)494-6054   FAX: (765)494-0558

>>FDA Safety Labeling Changes: August 4, 2004

> The problems are NOT with metformin, but with glitazones.
> Read the message carefully; the drug listed uses metformin
> on in conjunction with one of these, and the problems
> exist with or without metformin.

Could you elaborate with respect to pioglitazone?  I don’t see any
mention of it in the release.  Is there other evidence about
pioglitazone, or is the idea just that they’re similar enough to have
similar consequences?

news:2nuttgF4kebnU1@uni-berlin.de…
> FDA Safety Labeling Changes: August 4, 2004

> Yael Waknine

> Aug. 4, 2004 – The U.S. Food and Drug Administration (FDA) approved in May

revisions to drug safety
> labeling to advise healthcare professionals of the following changes:
rosiglitazone
> maleate/metformin is associated with risk of cardiovascular adverse events;

serious and potentially
> fatal infusion-related adverse events have been reported with the use of

alemtuzumab; intestinal
> angioedema has been reported with use of captopril; and indinavir sulfate

may increase plasma levels
> of sildenafil, tadalafil, and vardenafil.

> Rosiglitazone Maleate/Metformin HCl (Avandamet) Associated With Risk of

Cardiovascular Adverse
> Events

> On May 19, the FDA approved changes to the safety labeling for rosiglitazone

maleate/metformin HCl
> tablets (Avandamet, made by SB Pharmco), warning that thiazolidinediones

(alone or in combination
> with other antidiabetic agents) are associated with risk of fluid retention

that may exacerbate or
> lead to heart failure.

> The warning was based on results of trials involving a total of 876 patients
with long-standing
> diabetes and a high prevalence of related complications. An increased

incidence of edema, cardiac
> failure, and other cardiovascular adverse events was observed in patients

who received rosiglitazone
> and insulin concurrently compared with those who received insulin alone.

> Results of a double-blind study involving 112 patients with chronic renal
failure showed no
> difference in incidence of cardiovascular adverse events in patients

administered rosiglitazone in
> combination with insulin compared with insulin alone.

> The FDA recommends that patients treated with rosiglitazone

maleate/metformin in combination with
> insulin be monitored for cardiovascular adverse events.

> Rosiglitazone maleate/metformin is indicated as an adjunct to diet and

exercise to improve glycemic
> control in patients with type 2 diabetes mellitus already being treated with

the two medications and
> not adequately controlled with metformin alone.

> Alemtuzumab (Campath) Associated With Infusion-Related Events

> On May 19, the FDA approved changes to the labeling for alemtuzumab

(Campath, made by Ilex
> Pharmaceuticals) to warn of the associated risk of infusion-related events,

including hypotension,
> rigors, fever, shortness of breath, bronchospasm, chills, and/or rash.

> The warning was based on postmarketing reports of infusion-related events,
including syncope,
> pulmonary infiltrates, adult respiratory distress syndrome, respiratory

arrest, cardiac arrhythmias,
> myocardial infarction, and cardiac arrest.

> The FDA recommends that patients be carefully monitored during infusions.

Gradual escalation to the
> indicated maintenance dose is required at therapy initiation and after

therapy interruptions of
> seven days’ duration.

> Alemtuzumab is indicated in the treatment of B-cell chronic lymphocytic

leukemia in patients who
> have been treated with alkylating agents and who have failed fludarabine
therapy.

> Captopril (Capoten) Associated With Risk of Intestinal Angioedema

> On May 7, the FDA approved changes to the safety labeling for captopril

(Capoten, made by Par
> Pharmaceuticals and others), to warn of the risk of intestinal angioedema in

patients treated with
> angiotensin-converting enzyme (ACE) inhibitors.

> The FDA has received reports of patients presenting with abdominal pain with

or without nausea or
> vomiting, in some cases having no prior history of facial angioedema and

normal C-1 esterase levels.
> Angioedema was diagnosed by abdominal computed tomography, ultrasound, or at
surgery. Symptoms
> resolved with discontinuation of the ACE inhibitor.

> The FDA recommends that intestinal angioedema be included in the

differential diagnosis of patients
> taking ACE inhibitors and presenting with abdominal pain.

> Captopril is indicated in the management of hypertension and treatment of

congestive heart failure,
> left ventricular dysfunction after myocardial infarction, and diabetic
neuropathy.

> Indinavir Sulfate Increases Plasma Levels of Sildenafil, Tadalafil,
Vardenafil

> On May 7, the FDA approved changes to the safety labeling for indinavir

sulfate capsules (Crixivan,
> made by Merck), warning of drug interactions with concurrent administration
of sildenafil,
> tadalafil, or vardenafil.

> According to the FDA, indinavir sulfate may significantly increase plasma

concentrations of these
> medications and result in an increased incidence of related adverse events,

including hypotension,

- Hide quoted text — Show quoted text -

> visual changes, and priapism.

> Indinavir sulfate is indicated in the treatment of HIV infection.

> Reviewed by Gary D. Vogin, MD

> —————————————————————————-
—-

> Yael Waknine is a freelance writer for Medscape.

> Medscape Medical News is edited by Deborah Flapan, assistant managing editor

of news at Medscape.

> Send press releases and comments to n…@webmd.net.

> http://www.medscape.com/viewarticle/484948?src=mp

Maybe I don’t understand this well enough but this appears to refer more to
the Rosiglitazone maleate part rather than the Metformin part as the safety
risk.

Bill

<schuylercol…@charterinternet.com> wrote:
>I took my blood sugar just now and to my amazement, it is "99!" It has
>dropped nearly three hundred points in 5.5 hours with no medication of
>any sort. My blood is flowing like water! Very thin. I bled all over my
>clothes when I stuck my middle finger on my left hand.

Why does that surprise you? It doesn’t surprise me. it just means that
you are producing some insulin, just not enough and at the wrong time.

Read Jennifer, start testing to a system instead of randomly, and you
will start to understand what is happening after you eat and what you
need to do to get a degree of control.

Cheers, Alan, T2 d&e, Australia.
Remove weight and carbs to email.
—
Everything in Moderation – Except Laughter.

- Hide quoted text — Show quoted text -

> "Peanutjake" <peanutjak…@usa.com> wrote in message
> news:2nv2j2F53ggkU1@uni-berlin.de…
> > Danish health authorities ban some Kellogg products, saying they could
> harm children

> > CHRISTIAN WIENBERG

> > Associated Press

> > COPENHAGEN, Denmark – Danish health officials said Wednesday they have
> banned several
> > vitamin-enriched products of U.S. breakfast cereal maker Kellogg, saying
> they could be harmful if
> > eaten regularly.

> It is likely political rather than content of the cereals. Has the U.S.
> recently banned any Danish products?
> What contry is the cereal to be manufactured in? Possibly someplace
besides
> Denmark? does Kellog
> have a manufacturing facility in Demark?

BJ, not every decision in the world is political, or based on the American
view. Kellogg puts way too much crap in it’s "special brew" cereal, and the
Danes don’t like it. It’s simple really.

Beav

>the real problem with kelloggs products is that they are shit, which
>also isn’t in the article  - try learning how to tolerate

The brand is irrelevant. It’s the contents that matter. Processed
cereals.

Cheers, Alan, T2 d&e, Australia.
Remove weight and carbs to email.
—
Everything in Moderation – Except Laughter.