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Pharmaceuticals/Drugs

Treatment and Support for Substance Use Disorder

  • Posted Apr 16, 2019
  • hchadmin

Are you concerned that you, a family member or friend may have a substance use disorder (SUD)? SUDs occur when the recurrent use of alcohol and/or drugs causes clinically significant impairment, including health problems, disability, and failure to meet major responsibilities at work, school, or home. It's necessary that you educate yourself about the support that may be available to you or that you may need to provide to others in order to achieve a sustained recovery.

The National Institute on Drug Abuse (NIDA) offers the following information if you think you might have an addiction:

•It's important to know that addiction can be successfully treated. Contact your primary care physician who can help coordinate your care and refer you to a specialist, if needed. If you don’t have a primary care physician, just visit your insurance carrier’s website, look for the “find a doctor” area and follow the instructions. Or, visit the Substance Abuse and Mental Health Services Administration (SAMHSA) website for more information and resources.

•It takes a lot of courage to seek help because there is a lot of hard work ahead. However, treatment can work, and people recover every day.

•Your treatment approach must be tailored to address your specific substance misuse pattern and also your substance-related medical, psychiatric and social needs.

•There are different kinds of addiction specialists who will be involved in your care, including doctors, nurses, therapists, social workers, and others.

•Behavioral treatment (also known as "talk therapy") can help you engage in the treatment process, change your attitude and behaviors related to substance misuse, and increase your healthier life skills.

•Medications are available to treat addictions to alcohol and opioids (heroin and pain relievers). Other medications are available to treat possible mental health conditions.

•Self-help groups can extend the effects of professional treatment. These groups can be particularly helpful during recovery, as they are a source of ongoing communal support.

If you have an adult family member or friend who is struggling with the misuse of alcohol and/or drugs, NIDA offers the following tips:

•Recognize that you can't fix the problem by yourself. If someone you care about has asked for help, he or she has taken an important first step. If that person is resistant to help, perhaps you can at least convince him or her to get an evaluation from a doctor.

•You can always take steps to locate an appropriate physician or health professional, and leave the information with your friend or family member.

•Emphasize to your friend or loved one that it takes a lot of courage to seek help for a drug or alcohol problem because there is a lot of hard work ahead. But assure them that you will be supportive in their courageous efforts.

•The pressure of family and friends sometimes compels people to enter treatment. However, it's better that you focus on creating incentives to at least get the person to a doctor.

•If your friend or loved one was previously treated and then relapsed, they have already learned many of the skills needed to recover from addiction and should try it again. 

•People being treated or recovering from SUDs relapse about as often as do people with other chronic diseases such as hypertension and diabetes. Treatment of any chronic disease involves changing deeply imbedded behaviors, and relapse sometimes goes with the territory.

•Encourage your loved one to participate in a self-help group during and after formal treatment. These groups can be particularly helpful during recovery, as they are a source of ongoing communal support.

You may also consider contacting your site Employee Assistance Program (EAP).  Your EAP is a confidential resource that provides counseling, information and referral services to help address personal, family or work-related concerns. These services are provided to you and your family members free-of-charge as one of your employee benefits.

As your trusted health partnerf or life, Holy Cross Hospital is committed to providing resources that promote well-being though body, mind and spirit and is dedicated to helping you Live Your Whole Life.


[Disclaimer: Trinity Health is a Catholic health care facility that is firmly committed to maintaining fidelity to its Catholic identity by closely conforming to the Ethical and Religious Directives for Catholic Health Care Services (ERDs). The links provided here are independent sites and have no obligation to provide information that is always congruent with the ERDs. Trinity Health cannot guarantee their content and ask for your discretion when using information from these sites]

 

This years last word on the use of the new anticoagulants

  • Posted Dec 31, 2012
  • Alan Niederman, MD, FACC, FACP

On July 27th I blogged about the 3rd musketeer apixaban, or as it will be known, Eliquis.  This is the last of the new oral anticoagulants to be approved (full disclosure: the Holy Cross Jim Moran Heart and Vascular Research Institute participated in this study, and I was a sub-investigator).  Why approval took so long is not clear.  It was the only drug of the three that had a mortality difference (i.e. if you took it versus taking warfarin, you had less chance of death).

Like the other two drugs, Xarelto and Pradaxa, this drug does not have a specific antidote in the case of active significant bleeding.  Eliquis will need to be taken twice a day like Pradaxa.  I personally believe that the once a day Xarelto is a better option for patients. Eliquis maybe a better option than Pradaxa.  It was superior to warfarin in preventing strokes 1.27% vs 1.60%.  It had significantly less bleeding episodes than warfarin  2.13% vs. 3.09%.  Any death 3.52% vs 3.94% and death from cardiovascular cause 1.80% vs. 2.02%.

To put these numbers in a more rational way, for every 1,000 patients treated with Eliquis instead of warfarin, six strokes would be avoided, major bleeding would be avoided in 15 patients, and death would be avoided in eight.  Small numbers but this is how we make changes.  The question of how much this costs society is not certain.  I am sure that analysis is being done to add up all the costs, but I have not yet seen it.

How your doctor will decide which one of the musketeers is for you, if any, is not clear.  None of these agents have been or will be subjected to the needed test of which agent is more effective "head to head." This is where the dreaded "drug detail" dance starts.  People will come to see me to convince me of the value of their drug versus the other drugs.  Lucky for me, none of them get to see me since I take no samples, and I will sign for nothing.  My choices are based on evidence.   The same that I present in my blogs.

One last piece of news: as I have blogged about before, there was an attempt to use these drugs in patients who have mechanical heart valves.  Nope.  The FDA has now formally declared to cease and desist, and the study (RE-ALIGN) has been permanently halted.  This is unfortunate as it would have been nice to use these drugs.  I do not believe that the dosing was correct.  We use higher doses of warfarin in this setting and so I believe we needed higher doses of the newer drugs.  It is unlikely that this will be accomplished.

As 2012 comes to a close, I would like to thank you my readers for giving me some time in your busy lives to read my blogs.  I hope that they have provided you a better understanding of the issues that I have presented.  As we head over the fiscal cliff, Medicare providers face an almost 30% cut in fees across the board.  With or without the cliff, angioplasty procedural fees and electrophysiology procedural fees have been reduced by 20% for 2013.  I would like to think that when I perform angioplasty on a patient with an MI, that it is worth something.  I guess it is just 20% less than last year.  Is this any way to run medicine?

Happy New Year.  I wish all my readers and patients happiness and good health in the years ahead.


Throw away your niacin (Part II)

  • Posted Dec 25, 2012
  • Alan Niederman, MD, FACC, FACP

This part of the story surprises even me.  The HPS-2 THRIVE study was stopped by Merck this past week.  This was a huge study run by Oxford University in England.  It utilized 14,741 patients from the United Kingdom and Scandinavia and 10,932 patients from China.  Hold up!  What does this say about China?  Have they finally succumbed to the diseases of the West?  Does any research get done in the United States anymore? After four years of follow-up, this study showed no benefit in adding niacin to a statin in reducing cardiovascular events.  Further, there was a statistically significant increase in some types (not specified) of non-fatal serious side effects.  The story here is even more bizarre than AIM-HIGH.

First, the background: The compound being tested was a combination drug.  The two drugs in the pill were extended release niacin, known as Niaspan, and a new drug laropiprant. The drug laropiprant is a DP1 blocker and works on vascular cells to prevent flushing.  The concept was that the laropiprant would block the side effect of the flushing in the niacin so that people would take the medicine.  This drug has been tested before and was used for a period of time in the United States in 2008.  The FDA issued a "non-approvable" letter to Merck after their first United States study, and they were forced to do further work on the compound.  The  compound known as Tredaptive or Cordaptive is being sold and used in Europe, but now the European regulatory bodies will look into the compound based on this study.

Still not satisfied with the answer, the naysayers (like the NRA) blame everyone and everything except the obvious.  Maybe niacin just doesn't work?  Among the reasons that this study did not prove their point was because this study was all-comers.  This meant that the baseline HDL was 50 mg/dl.  Raising the HDL by 20% in that case would mean a HDL of 60 mg/dl.  I see two points here.  The first is that it says something when a group of patients who have cardiac disease have a mean HDL of 50 mg/dl.  That is felt to be rather high.  The risk is felt to be the greatest in low HDL like 30 mg/dl.   Maybe the whole idea of HDL and raising it to prevent cardiovascular outcomes is not correct.  Maybe Earth is not the  center of the universe.  Why didn't Merck only enroll those that had the lowest numbers?  The second - and perhaps more profound - reason that this study failed is because no one really knows what laropiprant does or what deleterious effects it might have. What if it counters the effect of Niaspan on the artery?  The study should have included more tiers, one of which would have been laropiprant alone.  Why did it not?  As I have mentioned before, the cost of all this is astronomical and getting higher all the time.  We are approaching a point where drug development may come to a grinding halt because the cost of development does not allow a company to obtain a profit.

Where do we go from here?  Eat sensibly, lose weight, stop smoking and take as much statin as you can.  The rest seems to be a waste of time and money.  We as a society will have to wait for the next big idea.  We are out of them for the time being.  I only hope that when the idea comes, we will have the ability and will to test it and bring it to market. I wish all of you a Happy Holiday season.


Throw your niacin away (Part I)

  • Posted Dec 20, 2012
  • Alan Niederman, MD, FACC, FACP

I have blogged about the uselessness of niacin in the past in a long blog piece about the AIM-HIGH study that began on May 31,2011 and ended on June 7, 2011.  The point of those blogs were that niacin, when added to statin, did not provide clinical benefit.  As always in medicine, and lately in every other walk of life, the naysayers come out and say that these facts don't matter.

Let's stop for a minute and consider why you as a patient and we as doctors give you a drug.  The simplest reason is that there is a clinical benefit.   When you take an antibiotic, your infection goes away.  When you take an antacid, like Zantac, the burning in your stomach stops.  When you take a statin, the clinical benefit is not that your LDL goes down.  The LDL number is a marker for the effect of the statin.  The reason you take the statin is that your clinical benefit is statistically less heart attacks, episodes of unstable angina and death.  This aggregate number is significant when compared to placebo.  The lower your LDL number goes, the less likely you are to have a clinical event.  In spite of what your doctor likely tells you, there is no LDL number too low.  35 seems to be optimal as I have explained in other blogs.

So how did we get to this point?  In the early days of trying to find a "cure" for atherosclerosis, niacin was found to  increase HDL levels by up to 20%.  This however was with doses of niacin that are generally intolerable: one to three grams a day.  Most people have trouble taking 500 mg a day.  These studies were performed before statins.  They utilized relatively small numbers of subjects given the numbers of patients needed today.  One reason is that in today's work, statins are so effective that very large numbers of subjects are needed to prove the point and so the clinical benefit.

In a recent meta-analysis published in Atherosclerosis (2010 Jun;210(2):353-61) entitled "Meta analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis," the authors reviewed 11 randomized trials.  In those trials combined, 2,682 active patients and 3,934 control patients were used.  Nowadays, each trial would be this big.  In the AIM-HIGH trial alone 3,500 patients were studied.  As discussed in the blogs mentioned above, AIM-HIGH was sponsored by NIH and stopped early as it was futile.  It found "That high dose, extended-release niacin offered no benefits beyond statin therapy alone in reducing cardiovascular-related complications."  Once again I must stress that the average LDL in this trial was 71 mg/dl.  That means that some patients had LDL's in the low 50's.  This remains the gold standard.

So we have the failure of niacin, fibric acids like Lopid and unfortunately the new class of drugs know as CETP inhibitors like torcetrapib.  Hope in medicine springs eternal, and at the end of all the articles about the failure of AIM-HIGH was a plea to await the results of the final trial called Heart Protection Study 2 Treatment of HDL to Reduce the Incidence of Vascular Events.

Be careful what you wait for...


Aspirin...again

  • Posted Dec 13, 2012
  • Alan Niederman, MD, FACC, FACP

I have blogged about aspirin many times dating back to September 19, 2009.  Yes I have been doing this for a long time.  What is old is new again in an article published in Circulation online last week.  Entitled "Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin" (DOI: 10.1161/CIRCULATIONAHA.112.117283), this article helps to dispel yet another Urban Legend, that of the concept that certain people do not respond to aspirin appropriately.

This is actually a big deal if it was true.  Taking aspirin after a myocardial event decreases your risk of death by 20%.  Like the discussion of "more taste, less filling" or the tooth fairy, you either believe in aspirin resistance or you don't.  A great deal of money is spent on testing for something that most people feel doesn't exist.  This article is just one in a long line of articles.  This article also helps disspell another myth, that of enteric coating.

Just because it should work doesn't mean it does work.  Enteric coating was promulgated to reduce the risk of GI bleeding.  This "proof" was, however, incorrectly done.  What enteric coating does is reduce the risk of visible stomach lining lesions.  The proper study, never done, would have been to assess for all bleeding not only for those visibly seen.  This is because the bleeding is based on the prostaglandin function of aspirin and not the irritative function of aspirin.  You can get GI bleeding from aspirin by giving it rectally. Similarly, Plavix causes GI bleeding and it is not based on an irritative basis.

What is the science?  We believe that approximately 50 mg of aspirin is needed to inhibit the platelet receptor in question.  This, however, requires the aspirin to be perfectly absorbed from the stomach.  This definitely does not happen all the time.  Therein lies the problem with the enteric coating.  When the 400 healthy subjects in this study were given enteric coated aspirin, none were found to be aspirin resistant by common tests.  49% did not have proper activation at 4 hours, and this dropped to 17% at 8 hours.  Of the 17%, after one week of aspirin therapy, none were found to be resistant.

What have we learned?  Enteric coating does little to protect you from GI bleeding in aspirin use.  It does however interfere with the acute use of aspirin such that in emergency situations, regular aspirin should be used and preferably chewed.   It does not seem to help if you chew enteric coated aspirin. Good luck with finding regular aspirin in a hospital, however, since most - if not all - of the aspirin has been replaced with the enteric coated aspirin.  Long term administration of any form of aspirin eradicates the apparent resistance.

The naysayers have already appeared.  This study utilized healthy people, and their conjecture is that "sick" patients are different.  This may or may not be true.  It has yet to be determined but probably never will be because it takes time and money to do this work, and it is unlikely to get funding.

I can guarantee we have not seen the last on this topic.  Over 150 years and we still do not understand the "simple drugs."


A stake through the heart (Part II): The rise of Gdufa

  • Posted Dec 06, 2012
  • Alan Niederman, MD, FACC, FACP

Who or what is Gdufa?

Is Gdufa the answer to the problem of generic drug manufacturing and the lack of transparency and accountability in the entire process?  Can we return to a time of naivety when we never thought or worried about this subject?  Should we return to that time?

Gdufa stands for Generic Drug User Fee Amendments of 2012.  It actually goes by Gdufa, and if you type that into Google, the information about the act is what shows up.  I will summarize its purpose and what it hopefully means for everyone.  First, some surprising numbers.

Since 1984 over 8,000 generic drugs have been approved by the FDA.  In 2011, 78% of all drug prescriptions were for generic drugs, and the estimated cost savings was $931 billion.  Almost a trillion dollars in one year alone.  I, and others like me, would have thought that somehow this savings should be protected as well as the public's safety.  Isn't that what the FDA does?

It seems that isn't the case.  Why?  The same reason things usually don't get done: money.  In the era of deficits and "small government," the protection of the American public took a backseat to expediency.  The system got a trillion dollars in savings and you got...who knows.  Somehow Afghanistan can be billed to us the taxpayers but drug protection...not so much.

Well our problem is solved.  The money to do what is needed is coming from the foxes guarding the hen house.  The generic drug manufactures are going to provide $299 million a year in inflation adjusted dollars. This represents one half of 1% of generic drug sales.  What did the drug manufacturers get?  Currently it takes 31 months on average to approve a new generic drug.  Seriously, I'm not making this up.  2,500 applications were awaiting approval at the time of the bill passage.  This time will be significantly shortened, and the FDA will have to be accountable to Congress.  The FDA promises to review 90% of the new applications within 10 months of the submission date by the 5th year of the agreement.

What did we, the people, get?  Currently the FDA inspects foreign drug manufacturers once every seven to 13 years.  I'll bet that scares them.  Now they will be inspected every two years with the riskiest sites being inspected more frequently.  Further, all facilities that manufacture drugs and their components will now be identified.

Certainly this is a good start.  Execution will be the problem as always.  It is hard for me, and I'm sure for you, to understand how this was not always the way it was.  Is glass in generic Lipitor the only problem?

One final note: the bill strives to create an improvement in, as they call it, "regulatory science."  Basically this refers to testing and maintaining the generic drugs to ensure they meet the potency and same activity that the formal product has.  When there were just a few drugs and manufacturers, this was not such a problem.  If 15 companies make the same generic Lipitor, are they all the same?  Can we choose or does the pharmacy just give us the pills and tell us, as my mother used to say, "take your medicine"?

I can guarantee you that this event, the finding of glass in generic Lipitor, is just the first in what will be a long line of problems.  We must as a country solve this problem and devise ways to protect patients from drugs that do not work or are harmful.


A stake through the heart (Part I)

  • Posted Dec 04, 2012
  • Alan Niederman, MD, FACC, FACP

There appears to be no bottom to it.  I have attempted to inform you, my readers, about a problem that no one has an answer to and very few people seem to care about.  It's almost as if the phrase "what I don't know can't hurt me" has infected our entire national psyche.  The what we don't know is what is in our drugs.

Of all the drugs that patients waited to become generic, Lipitor stood out.  It was necessary for so many patients, and it was expensive.  Insurance companies would wrongly point patients to other less expensive, but  not as powerful, drugs like it was OK.  But, as it became clear to us that those that suffer from coronary disease need LDL levels less than 70, the power of Lipitor became more apparent.  Lipitor was the largest selling drug in the world year after year, after year: $16 billion a year.

How is it possible that the company that brought the generic to market could be so careless as to have it tainted?  Not only does it show just how broken the system is, but now the company has completely shut down production of atorvastatin.  Does no one care?  Are we doomed?  Is this the new normal?

How does glass get into a drug?  Why can't we document and secure our drug sources?

Let's take a look at the company.  As reported in the New York Times on November 29, 2012, Ranbaxy Pharmaceuticals was in a heap of trouble before this incident.  Ranbaxy is a subsidiary of a large Japanese pharmaceutical company called Daiichi Sankyo.  As an interesting factoid, Daiichi Sankyo was the company that found the substance in Red Rice Yeast that became lovasatin.  Second factoid: lovasatin is also found in oyster mushrooms.  Yes, all my friends who only want to take "natural" drugs, that's what lovastatin is - natural.

Anyway, I digress.  Ranbaxy is operating under a consent decree issued on January 25, 2012.  I quote from the decree:
"These problems include failure to keep written records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from non-penicillin drugs in order to prevent cross-contamination; failure to have adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drugs to ensure that they kept their strength and effectiveness until their expiration date."

What did the government do?
I quote: "Among other things, the consent decree prevents Ranbaxy from manufacturing drugs for the U.S. market at certain of its facilities until those facilities can do so according to U.S. standards. To remove false data contained in Ranbaxy’s past drug applications and to prevent Ranbaxy from submitting false data to FDA in the future, the consent decree requires Ranbaxy to take actions such as:  hire an outside expert to conduct a thorough internal review at the affected facilities and to audit applications containing data from those facilities; withdraw any applications found to contain false data; set up a separate office of data reliability within Ranbaxy; and hire an outside auditor to audit the affected facilities in the future."

So...they manufactured the active drug in India at a plant that was not shuttered in India and assembled the drug here in the United States.  One would think that they would be extra careful, but apparently they don't think like one.  Ranbaxy had 43% of the market in October.

Folks, as Joe Biden would say, "If this is so screwed up, we are all in trouble.  Can Gdufa save us?" Read my next blog.


From bad to worse (Part III)

  • Posted Nov 13, 2012
  • Alan Niederman, MD, FACC, FACP

So we have a conundrum.  Which is better: utilizing a new drug that works all the time and is easy to use but has a major drawback or an old drug that does not have the drawback but is impossible to use?   The answer is, "Who knows?"  I will  lay out the facts.

As I have mentioned before, only about 60% of the patients who are "supposed to be anti coagulated" because they have atrial fibrillation are actually anti coagulated.  Surprisingly, the use of the newer anticoagulants has not altered that number. Let me list some of the reasons that this happens.  At times doctors just don't realize that it is important. Sometimes there is a disagreement between doctors as to how to proceed, and the patient becomes confused.  Sometimes the patient refuses to use the drug regardless of their doctor's request.  You can do anything you want as long as you understand the issue and the possible consequences. Many of these patients are older and frail and have many co-morbities that make it almost impossible to anti coagulate them properly.  We as physicians just basically give up as the hassle for everyone just doesn't make sense.  If you the patient are trying, but we the physician never get you anti coagulated, you are not protected anyway.

Even in the best of hands anticoagulation is only correct 60% of the time.  How do I know this?  That is how often the "experts," who did the work of drug approval on these drugs, got it right.  This number has been replicated many times, and so it is not exact but pretty darn close.  How can people take a drug that is only dosed right 60% of the time?

Further, as reported in the Archives of Internal Medicine (Arch Intern Med 2012; DOI:10.1001/archintmed.2012.4485) in an article titled "Persistence with therapy among patients treated with warfarin for atrial fibrillation,"  more that 60% of the people who started taking warfarin stopped after five years.  It gets better.  8.9% didn't fill their second prescription.  31.8% stopped after one year.  43.2% stopped after two years.  61.3% stopped by five years.  More to the point, the mean stop time was 2.9 years.  That means that half the people had stopped by that time.  This group of people were in Ontario and were 66 years or older.  They all had insurance.  In this country I'm sure the numbers would be worse.

What to do?  My opinion, the one that I share with my patients, is that these new drugs are far easier to use than warfarin and provide a stable effect.  I prefer Xarelto because the pills are not fragile, and it is taken once a day.  The risk of difficulty when someone bleeds is real, but we as physicians make choices all the time that play the odds.  You can't live life worrying about all the "what ifs."  If you really need to be anti coagulated, then you should take the best drug possible to avoid the strokes associated with the condition.  I believe that patients who have had bleeds, or have a condition that might lead to bleeding, should not receive these newer drugs.

It is early in the game, and these real issues will be worked out over time.  No one is going to spend the money to find an antidote that no one will use.  Progress in this field will allow us to modify the bad effects and retain the better treatment results.

Progress in medicine is not a straight line.


From Bad to Worse (Part II)

  • Posted Nov 08, 2012
  • Alan Niederman, MD, FACC, FACP

Pradaxa is once again in the news.  Two very different stories about the drug were published on November 2, 2012.  The first was published in the New York Times, written by Katie Thomas and is entitled "A Promising Drug With a Flaw."  The second is a FDA Drug Safety Communication regarding Pradaxa.

The FDA undertook a review of the bleeding episodes of Pradaxa to follow-up on a FDA Safety Communication of December 7, 2011.  This new safety study concludes that "the results of this Mini-Sentinel assessment indicate that bleeding rates associated with new use of Pradaxa do not appear to be higher than bleeding rates associated with new use of warfarin, which is consistent with observations from the large clinical trial used to approve Pradaxa (the RE-LY trial)."

The data according to the FDA report shows that intracranial hemorrhage, which is the most dreaded bleeding complication, occurs 1.8 to 2.6 times higher in new users of warfarin than Pradaxa per 100,000 patient days at risk.  The rates of gastrointestinal hemorrhage were 1.6 to 2.2 times higher for new users of warfarin than Pradaxa per 100,000 patient days at risk.  The excess bleeding in warfarin users is likely due to physicians' inability to control the effect of the drug on patients and the multiple interactions of warfarin with other drugs that patients are often given without a full understanding of their medical conditions.

So what is the problem that has the New York Times so spun up?  The problem is that Pradaxa has no way to be reversed.  It just has to "wear off," and in that time, the bleeding may not be controllable, and the patient can die.  Some conditions like intracranial hemorrhage are so devastating and unpredictable that it often doesn't matter what we do.  Further, although there is an antidote for warfarin, let me lead you through the steps.

First ,we have to figure out that you are on warfarin and that you are actually anti-coagulated. The data shows that this only happens about 60% of the time.  Second, you have to be "typed and crossed" to find out what blood type you are.  Third, the fresh frozen plasma needs to be unfrozen.  It can't be placed in a microwave.  It is put in a warm water bath and gently rocked back and forth.  I am not kidding.  You can hop up and down all you want, but you the doctor and you the patient  are not getting the fresh frozen plasma until the blood bank is good and ready to give it to you.  Then you have to administer it.  All of this takes precious time.  In the meantime, physicians do what we can, just like always, to support the patient.

The data to approve Pradaxa and Pradaxa itself need to be better understood.  First, we physicians give Pradaxa to any patient, but the oldest patient in the study to approve Pradaxa was around 80 years old.  The mean age in the RE-LY  study to approve was 71.4 +/- 8.6 years.  The older you are, the more likely you are to have a poor outcome.  Second, as I have blogged about before, the FDA made up the 75 mg dose.  The RE-LY study used both a 150 mg does and a 110 mg dose.

More - and there is plenty more - next week.


From bad to worse (Part I)

  • Posted Nov 06, 2012
  • Alan Niederman, MD, FACC, FACP

I have blogged recently about the disaster of contaminated drugs and about Pradaxa; both topics remain in the news. First, the contaminated drugs: this event is nothing short of a disaster. The company New England Compounding Center and its sister company, Ameridose, are both shut down. When the FDA tested 50 vials from one of the lots of the drug, all 50 vials were contaminated. In one lot, 83 of 321 vials had visual contamination of "greenish black matter," and 17 vials had "white filamentous matter." 29 patients have died, and a total of 404 cases have been identified. Most of these relate to injection of the material in the spinal column, but some relate to injection of the material into other joints like knees and shoulders.

Now a second problem has been added to the devastation of the first one. This problem is the development of an abscess at the site of injection. This abscess can extend into the space around the spinal cord known as the epidural space. This is a devastating problem. Perhaps not fatal but it can lead to paralysis and chronic pain. It is possible that some of these patients may need treatment the rest of their lives as the fungus may be controlled but never cured. This second infection seems to be occurring in at least 30% of the cases.

Further complicating the picture is that these secondary sites are occurring in patients who have been receiving treatment for the fungus, which is called Exserohilum. These infections can only be identified by MRI scans. Not much has been heard from the FDA, and there is speculation that the reason is pending Federal indictments. Certainly, this problem will require hearings and new legislation to mandate further protection of the public who rely on medication. This is another cautionary tale for those people who believe that States and not the Federal government should take care of their own.

In my blogs last month on trying to expand the use of Pradaxa, I mentioned that a study was underway to evaluate the use of Pradaxa in the anticoagulation of mechanical valves. This study, known as RE-ALIGN, has two arms. The first arm randomized patients immediately after surgery, and the second arm three months or later after surgery. The first arm has just been discontinued after an excessive number of strokes occurred.

The second arm continues. No new patients are being enrolled. This work is taking place in Europe and Canada. The dose of Pradaxa is the same dose that is being used for atrial fibrillation. This may not be the proper dose. When we use warfarin for the purpose of anti-coagulating valves, the INR level we use is 3-4. The level for atrial fibrillation is 2-3. The dose of Pradaxa used may simply be too small. Although not done clinically, the levels of Pradaxa in your bloodstream can be identified. The levels found in the first arm were lower than those compared to the atrial fibrillation group. This is what research is about. Entering the maze and trying to find your way out. Next...more "bad" press for Pradaxa.


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About Holy Cross Hospital

Holy Cross Hospital is a nonprofit, Catholic hospital in Fort Lauderdale, Florida, dedicated to innovative, high quality and compassionate care. For nearly six decades, Holy Cross has continuously expanded its services to provide leading-edge care for their patients in Florida and for those from elsewhere in the United States. Holy Cross also offers an International Services program to ensure that patients from outside the U.S. receive the care they need.

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