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FDA investigating the safety of Benicar
 Moderated by: Prof Trevor Marshall Page:    1  2  3  4  5  6  ...  Next Page Last Page  
 

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Prof Trevor Marshall
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 Posted: Fri Jun 11th, 2010 13:09

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Well, it had to happen - FDA has at last noticed that Benicar is affecting Cardiovascular disease in Th1 individuals - specifically Diabetics.

http://www.reuters.com/article/idUSN1113920620100611

Click here for the official FDA announcement, with more details.

And here is an article in Nephrology Times which gives more details about the dosing - 40mg once a day

Since we first told the FDA (in 2005) that Benicar had a profound effect in sick individuals, and that frequent dosing was important, nobody at FDA has expressed interest in finding out how Benicar actually works.

Just this morning I submitted a set of slides to the FDA for a presentation I will be doing for a Public Hearing later this month, on the way FDA evaluates drugs.

If anybody's Doc gets nervous after reading the press releases, I will be happy to chat with them about what we have found -- that using the correct dosing of Benicar, the MP dosing designed to keep a continuous supply in the bloodstream, cardiovascular disease is actually reduced, and plaque gradually disappears from the carotid arteries.

I will keep you up-to-date as we continue to work the issue of Benicar's real actions with the FDA...

Meanwhile, please remember that when you stop Benicar your organs lose its protection. It is dangerous to stop benicar cold-turkey. Not very dangerous, but several members have gotten very ill after their physicians abruptly stopped prescribing the drug.

..Trevor..

  ps: Here is a report on the baseline (starting) observations for the ROADMAP trial
 
 

Last edited on Fri Jun 11th, 2010 14:27 by Prof Trevor Marshall

scooker48
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 Posted: Fri Jun 11th, 2010 15:24

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I view this as an opportunity, not a threat.

Sherry



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Barney
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 Posted: Fri Jun 11th, 2010 17:12

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Ditto Sherry,

I am the one the FDA should look at. I have lost a kidney to sarc pre MP, I have taken large amounts of Benicar for 5 1/2 yrs now. My blood sugars have been thru the roof a lot and I have been unable to use any diabetic meds including insulin w/o vomiting, severe pain, etc. I am having to go very strict on the sugar and flour now to get it down and I am still walking the face of this earth. HELLO!!!!!!!!!!!....thanks to BENICAR.

HANG IN THERE, WE WILL MAKE IT!!!!BARNEY:D

Last edited on Fri Jun 11th, 2010 17:12 by Barney



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Prof Trevor Marshall
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 Posted: Fri Jun 11th, 2010 18:56

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Sherry, I agree. That is why I put the links to the full articles up online. If Doc mentions a newspaper article, we will have the actual detailed stuff, and can explain why this isn't anything new (to us)...
 

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 Posted: Fri Jun 11th, 2010 22:29

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My observations after reading the provided charts...

ROADMAP was larger study with 3+ years with 40mg Benicar.
ORIENT was smaller study with varying doses and end points.

Looks like both were treating a very ill patient population.

The death rate for both studies were about the same between Benicar vs. placebo,
but the cause of death appears to have been different.

ORIENT's death rate for both Benicar and placebo was 7%
ROADMAP's death rate was 1% for Benicar vs. 0.7% for placebo

Both studies allowed and had most of patient population taking multiple anti-hypertensives. This is another difference between these studies and the Marshall protocol.

Of course, in both studies the Benicar was taken once per day which provided stimulation of the immune system, but none of the anti-inflammatory protection provided when taken every 4 to 6 hours. :?

Last edited on Fri Jun 11th, 2010 22:32 by Joyful



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 Posted: Sat Jun 12th, 2010 07:03

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What doesn't jive is the "sudden cardiac death" rates and the other research that says Benicar reverses CAD. I wonder what the causes of those sudden deaths were? The reports state, " In considering the results of these trials, it is important to remember that numerous clinical trials with olmesartan as well as trials with other ARBs have not suggested an increased risk of cardiovascular-related death. And......these drugs and a closely related group of drugs called angiotensin-converting enzyme inhibitors (ACEIs) have been evaluated in many studies involving thousands of patients at high-risk for cardiovascular events, such as patients who had a previous heart attack or had heart failure. No increased risk of cardiovascular-related death has been reported in these trials and, in fact, some of these studies indicate ARBs and ACEIs are useful as treatments for certain patients at high-risk for cardiovascular events.

I am not trying to minimize the report because I do think it is something that needs further investigation. I just wonder if this particular group of people, either because of their individual risk factors or other medications (as Joyful noted), had special complications that lead to the increased cardiovascular events? In other words, why are these two groups different than other groups that were tested in regard to cardiac deaths?



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Joyful
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 Posted: Sat Jun 12th, 2010 11:22

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As I understand it, almost all drug trials purposely exclude people with preexisting conditions. That is, the people tested have one, and only one condition. The condition under study.

This means that typically they study people where if the condition is a Th1 disease, it is not very far along. And so most trials will not show the kinds of mortality that are commonly seen in people with multiple chronic conditions.

This also means that that they are not studying people whose level of disease that is too far along to stand the rigors of having the VDR switched on & off every day WITHOUT the palliation of keeping the Benicar levels high enough ALL THE TIME.

The early adopters of the MP were quick to learn that missing a Benicar dose could lead to an increase in symptoms... the inflammation would start to increase and they were aware of the cause (needing Benicar more often) and worked to find the optimal timing. These researchers did not have that understanding.

Not so long ago Alaska Dave posted that he was happy to discover how much easier his symptoms were when he finally (after many years on the MP) switched from q8h to q6h dosing. So even with our understanding, there is room for fine tuning the optimal approach. Most studies will not have patient feedback as an input into the structure of the trial.

The people in these studies were probably pushing themselves to keep life going at a 'normal' pace with three co-morbidities: diabetes, hypertension, and renal disease. They are probably not mentally prepared to watch for and respond quickly to cardiac symptoms. The researchers conducting the study didn't seem to be.

Add to that a drug that activates the VDR, thus stimulating their immune response, and you have a perfect recipe for exactly what they found, in my opinion.

It is easy to be caught unaware when the mindset is to treat various systems in the body as separate. But we know that the infections of chronic disease touch every organ and part of the body. And this includes the heart as all the blood in the body must be pumped through it every minute a person is alive.



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 Posted: Sat Jun 12th, 2010 13:01

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Joyful, a very well-thought out response to this FDA news!  I think you've made some very good points in your reply!  Let's hope that the FDA does not overreact to these studies without considering the points you have made ... the amazing results of the MP study and Dr Marshall's input.  I hope they might finally see the benefits of higher dosages of olmesartan and how it activates the VDR.  It is certainly not JUST a hypertensive drug and that is how most in the medical community continue to see it! 



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titta
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 Posted: Sat Jun 12th, 2010 15:14

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Multipharmacy appears to be one problem.
And of course, it is necessary to know how to use olmesartan.

One example: You can turn off fire blowing air. (a candle)
                       You can turn on fire blowing air.  (a fire bigger than that of a candle).

Excuse my language, sounds rather German.

Those people taking part in those studies surely suffered from a"bigger fire" inflammation...

Titta



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Joyful
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 Posted: Sat Jun 12th, 2010 23:09

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Excellent analogy titta! :)



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Prof Trevor Marshall
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 Posted: Sun Jun 13th, 2010 15:29

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Bane sent me a study just published in Lancet Oncology showing a 25% increased risk of Lung Cancer in people taking ARBs for blood pressure (with the wrong dosing, of course).

Here is the news release, I will post more details in the next day or two:

http://www.eurekalert.org/pub_releases/2010-06/uhcm-uhc061110.php

..Trevor..

Bane
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 Posted: Sun Jun 13th, 2010 15:41

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Dr Trevor Marshall wrote:  
Bane sent me a study just published in Lancet Oncology showing a 25% increased risk of Lung Cancer in people taking ARBs for blood pressure (with the wrong dosing, of course).

Here is the news release, I will post more details in the next day or two:

http://www.eurekalert.org/pub_releases/2010-06/uhcm-uhc061110.php

..Trevor..



Common blood pressure drugs may raise cancer risk

http://www.reuters.com/article/idUSTRE65C2C120100613

Most patients in the trials (86 percent) took German drugmaker Boehringer Ingelheim's telmisartan, sold as Micardis, which has annual sales of more than $1.5 billion.

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 Posted: Mon Jun 14th, 2010 01:01

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Visiting Professor Lecture Series, organized by the Center for Drug Evaluation and Research, a division of the FDA

http://mpkb.org/home/publications/marshall_fda_cder_2006

"What you see looking at this table is that there are an awful lot of numbers which are below one. Any of these numbers that are below one indicates that that drug is going to have a very significant impact on that receptor at the normal concentrations that these drugs are administered in pharmacology. Telmisartan, for instance, doesn’t really affect the thyroid receptors, the MCR or progesterone receptors very much, but it really knocks out the VDR and PPAR-gamma and PPAR-alpha."

Prof Trevor Marshall
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 Posted: Mon Jun 14th, 2010 05:32

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My in-silico discovery that Temisartan turns off the VDR, directly opposed to Olmesartan turning it on, was confirmed by the study Bane posted in April (as well as our anecdotal experience from testing it):

Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters.


http://www.ncbi.nlm.nih.gov/pubmed/20222053


ATP-binding cassette (ABC)-transporters, such as P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) transport numerous drugs thus regulating their absorption, distribution and excretion. Angiotensin receptor type 1 blockers (ARBs), used to treat hypertension and heart failure, are commonly administered in combination therapy. However, their interaction potential is not well studied and their effect on ABC-transporters remains elusive. The study therefore aimed to elucidate the effect of various ARBs (telmisartan, candesartan, candesartan-cilexetil, irbesartan, losartan, olmesartan, olmesartan-medoxomil, eprosartan) on ABC-transporter activity in vitro. P-gp inhibition was assessed by calcein assay, BCRP inhibition by pheophorbide A efflux assay, and MRP2 inhibition by a MRP2 PREDIVEZ Kit. Induction of P-gp, BCRP and MRP2 was assessed by real time reverse transcriptase polymerase chain reaction and for P-gp also in a functional assay. Telmisartan was identified as one of the most potent inhibitors of P-gp currently known (IC(50)=0.38+/-0.2 microM for murine P-gp) and it also inhibited human BCRP (IC(50)=16.9+/-8.1 microM) and human MRP2 (IC(50)=25.4+/-0.6 microM). Moreover, the prodrug candesartan-cilexetil, but not candesartan itself, significantly inhibited P-gp and BCRP activity. None of the compounds tested induced mRNA transcription of P-gp or BCRP but eprosartan and olmesartan induced MRP2 mRNA expression. In conclusion, telmisartan substantially differed from other ARBs with respect to its potential to inhibit ABC-transporters relevant for drug pharmacokinetics and tissue defense. These findings may explain the known interaction of telmisartan with digoxin and suggest that it may modulate the bioavailability of drugs whose absorption is restricted by P-gp and possibly also by BCRP or MRP2.

Last edited on Mon Jun 14th, 2010 05:35 by Prof Trevor Marshall

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 Posted: Mon Jun 14th, 2010 09:04

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HI DR MARSHALL

This is Fred in WV.  On you post about about the "telmesartan with digoxin", I am on the Benicar and Digoxin, would this have any effect on me and my heart.  I have wondered if I should stop the Digoxin with the Marshall Protocol. 

When I started the MP the doctor took me off 2 other heart pills but keep me on the Digoxin.  I think the Digoxin was to make the heart muscle stronger?? This was because the ejection fraction was on the low side. I have been wondering about if I should stop the Digoxion for some time now.

Remember, we are all in this together and I am pulling for us.

Your friend in Sarcoidosis
Freddie



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Prof Trevor Marshall
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 Posted: Mon Jun 14th, 2010 09:42

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Freddie,
Info on Digoxin can be found at Wikipedia
http://en.wikipedia.org/wiki/Digoxin

You might check the concentration you are taking against the 0.8 μg/L they mention there.

Adverse events do not seem VDR-related, and the molecule is too big to affect VDR, but I am not sure about PXR. It should be OK. Still, I would discuss with Doc whether you still need it, or can wean it slowly.
 

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 Posted: Mon Jun 14th, 2010 10:37

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Modest lung-cancer signal with angiotensin-receptor blockers

http://www.theheart.org/article/1087349.do

"This is a modest increase, similar to that seen with passive smoking; it's not a massive increase," lead author of the study, Dr Ilke Sipahi (University Hospitals Case Medical Center, Cleveland, OH), told heartwire. Nevertheless, this is the first time such an association has been made, he said. And although the number needed to treat to cause one excess cancer was calculated to be 105 patients for four years, meaning the risk for the individual patient is not huge, "given the millions of patients on these drugs, this is an important number, because it gives us an idea of potentially how many excess cancers could be caused by these medications. On a population level, I think these are very concerning signals."

Dr Michael D Peake (Glenfield Hospital, Leicester, UK), a spokesperson for the UK Lung Cancer Coalition, who was not involved in this research, told heartwire that the increase in lung cancer seen in this meta-analysis with ARBs "is fairly small." The risk of lung cancer is around 200% to 300% higher in a smoker than in a nonsmoker and is increased by about 60% in a person with a family history of lung cancer compared with an individual with no family history, he said.

"In this context, it's a relatively small risk, but if applied to large numbers of people, it might be quite important," he explained. The data are interesting but "would not stop me personally from taking an ARB if I needed one; it's not sufficiently powerful to influence prescribing at this point," he added.

-----------------------------------------------------

"Nevertheless, questions remain as to whether ARBs are associated with malignancies and whether there should be concern about a single drug, telmisartan, or all ARBs, he says."

"In the interim, ARBs, particularly telmisartan, should be used selectively, he urges. They can be reserved for patients with intolerance to ACE inhibitors, "which will also save money for healthcare systems, since nearly all ARBs are proprietary and ACE inhibitors are generic."

Last edited on Mon Jun 14th, 2010 10:57 by Bane

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 Posted: Wed Jun 16th, 2010 13:38

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Angiotensin-Receptor Blockers Linked to Elevated Risk, But Some Doctors Aren't Convinced

http://abcnews.go.com/Health/HypertensionNews/study-links-popular-blood-pressure-drugs-cancer/story?id=10909261

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 Posted: Wed Jun 16th, 2010 14:26

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At the risk of being considered a moron, how are going to defend the use of Olmesartan to the FDA?

I can grasp some of the science presented, and am a firm believer in the MP.  But why are the studies showing a higher cardiovascular death rate flawed?

With puzzlement,

Sherry

 

 



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Terri R.N.C.
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 Posted: Wed Jun 16th, 2010 15:52

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Hello Dr.Marshall,

First of all I would like to thank you for giving me my life back.  I have been on program for about 22 months now and I am doing impressively better.  I'm going to go back to work within the next few weeks.  I just have to interview for the first time in 15 years:shock:!  I will post my recovery soon as my most recent post was lost after spending an hour on it.  I'm back in nursing school working on my "Nurse Practitioner" degree.  My MD is so impressed with my recovery that I will be his "MP Nurse" after I complete my degree (about 2.5 years to go).  I'm writing to you in concern for my fiance.  He has Metabolic Syndrome.  He is a typical Th1 patient.  Cholesterol is elevated, elevated blood sugar, high blood pressure, you get the picture.  I have started him on Benicar but he can only tolerate one tab/day.  He takes 40mg qhs.  He is a carpenter and works outside and gets too dizzy and weak when he tries to take 2/day.  After reading about the cardiac precautions especially for diabetics it has caused me to become alarmed.  My plan is to get back to working full time so that Mark can go full time on the MP.  I know that it will knock him out for at least 18 months.  My question to you is that do you think that he is better off not taking Benicar until he can commit to full time MP?  He could take the Benicar that has HCTZ mixed with it until he is ready to go full time with the protocol or do you think that he should continue with Benicar 40mg qhs along with a baby ASA qhs.  He states that he likes the way Benicar makes him feel however he gets too sleepy with the am dose.  He is responsible for building large corporate buildings and fears that he will miss handle dangerous machinery if he increases his Benicar.  I think that with time he can handle the increase  in Benicar, but then again he is in the sun all day.  He follows the same low D diet as I, but he has an awfully heavy duty muscle demanding outside in the 100* temp job (his job sucks).  Does Benicar work as well as it should even though one has to be out in the sun?  If not, I guess Mark will have to wait until the first of the year to commit to the MP.  I"m just concerned that he should stop taking the Benicar until then.  I have so much respect for you.  Everything that you said would happen to me has happened.  You are right on with your research and should have received the Nobel Prize by now.  My MD is the same one that Mark goes to and he likes Benicar.  He has suggested that Mark take Azor (Benicar with HCTZ).  I don't want to lose Mark.  I've already been a widow once before.  I know that these questions are very demanding, but the Benicar and Diabetes has me concerned.  I guess what I am asking you is what does this latest research mean to you?   Thank you for taking time to read this.  I hope that evryone is doing better.  I never thought that I would be, but if you get away from the medical doctors who are so narrow minded you will get your health back.:D 



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