FDA approved medicines, Off-label uses

When you have the American College of Cardiology (ACC) for cardiovascular diseases and the American Association of Clinical Endocrinologists (AACE) for endocrine related disorders holding classes for pharmaceutical sales people, is it any surprise that these drug reps are heavily promoting 'off-label' prescriptions. I quite imagine that some of these sales reps have then started classes for the companies they are employed by for more sales reps.

The blog here is written for medical professionals, but patients should learn from this and how their medical professionals may be promoting drugs 'off-label' for other than good medical reasons. The term 'off-label' means that the FDA has not approved the medicine for these uses.

The problem confronting us as patients is two-fold. Many physicians are receiving money to promote drugs and pharmaceutical drugs reps are promoting 'off-label' uses and dosages of many drugs. Then add to this that fact that many medical care providers do not stay current with the drugs entering the market or even many already on the market, and you have real problems because the doctors do not know what is approved or not approved for use by the FDA.

For 160 drugs tracked that are prescribed to U.S. adults and children, 21 percent were for off-label prescriptions totaling 150 million prescriptions. It is not surprising that 73 percent had little to no scientific backing. Psychoactive drugs had the highest level of off-label use. We should not be surprised that sales representatives are misrepresenting their companies' products. They systematically overemphasize the positive aspects and downplay or completely omit the negative features of their drugs.

This information is worth quoting. “The most recent study examined the quantity and quality of safety information that a random sample of primary care doctors in Montreal and Vancouver, Canada, Toulouse, France, and Sacramento, U.S. received from sales representatives. Serious adverse events were mentioned in just 5-6 percent of promotions, although 45 percent of promotions were for drugs with FDA “black box” warnings.”

To have a better understanding of the scope, pharmaceutical companies in Canada and the United States spend about $16.7 billion in 2009 on sales representatives (no wonder our medicines are so expensive!). These representatives come into doctors' offices with detailed information about their individual prescribing practices as well as free samples of their medicines. They use their personal relationships to promote the medicines of the company they represent, promote 'off-label' use of medications, and promote different dosages for the medications their company manufacturers.

“Restricting access needs to be accompanied by a multipronged education effort. Mansfield and colleagues have outlined an educational campaign based on studies of psychology students’ responses to persuasion, and medical students’ and physicians’ responses to pharmaceutical promotion that should be pursued throughout all levels of training and continued once doctors are in practice.

The fourfold objectives of this campaign are: explicitly educating doctors about decision making and how to evaluate evidence and promotion; helping doctors to understand that there is no proven method to enable them to have an overall positive benefit from promotion; helping doctors to understand their responsibility to avoid pharmaceutical and device promotion; and explicitly educating doctors about the most reliable sources of information.”

Hopefully, some of the last two paragraphs will come to fruition, doctors can get back to being doctors, and use FDA approved medications of the correct dosage and less 'off-label' use. There are some 'off-label' uses that are appropriate, but even then, the FDA should approve the use.

FDA Gives 4 Medication Tips to Older Adults

What is your age? I don't expect an answer, but I do wish to point out some problems as you age. I was surprised that the Food and Drug Administration (FDA) would put something out about medications for the elderly or older adults. I am especially surprised because they don't approve drugs for the elderly and most trials leading up to approval do not include the elderly.

Speaking from experience, the older one becomes, the more likely you will need additional medications. This is the worry because each addition can increase the risk of harmful drug interactions. Our bodies change and this can affect the way medicines are absorbed, leading to potential drug complications. Think about it, your liver and kidneys may not work as well, and this affects how a drug breaks down and leaves your body. Then consider changes in your digestive system and this can determine how fast drugs get into your bloodstream.

These are the four tips FDA advises for medications:

Take Medicine as Prescribed

Take your medications according to your health care provider's instructions. Do not skip doses or stop taking a medication until you have consulted your provider. I have know fellow patients who say they have talked to their doctor and stopped a medications, but in fact did talk to their doctor, but about something completely unrelated.

This does not mean that just because you are feeling better you can stop taking a medication. If you are experiencing side effects, also talk to your doctor about the side effects. You doctor may wish to change to another medication or reduce the dosage.

For chronic conditions, such as high blood pressure and diabetes, it is important that you take them as directed and continuously to maintain management of your condition. The dosage your doctor prescribes in based on tested and it is never wise to change the dose yourself.

Keep a Medication List

Keep a list of the medications you are taking. List the name of the medication, the dose, what it is for, and when you take it. Many leave important information of the list. If you take a medication three times per day, indicate this by time or meal if eaten with food. If it is AM or PM or both, indicate this.

Consider giving a copy to a trusted friend or family member is you live alone. Keep the list up-to-date if you add medications or the dose changes.

Be Aware of Potential Interactions

As you age, remember, you’re at higher risk for drug interactions.

Interactions can occur when:

• One drug affects how another drug works;
• A medical condition you have makes a certain drug potentially harmful;
• A food or non-alcoholic drink reacts with a drug;
• A medicine interacts with an alcoholic drink.
  

“Learn which interactions are possible. You can do this by carefully reading drug facts labels on over-the-counter drugs and the information that comes with your prescription medications, and by reviewing any special instructions with your health care provider. For instance nitroglycerin, which treats angina (chest pain related to heart disease), should not be taken with many erectile dysfunction drugs, including Viagra and Cialis, because serious interactions can occur. And some drugs should not be taken with alcohol, as symptoms such as loss of coordination and memory loss can result.”

“If you’re seeing multiple health care providers, tell each one about all of your medications and supplements. You also can ask your pharmacist about potential interactions.”

Review Medications with Your Health Care Provider

Schedule at least one annual review of your medications with your health care provider to confirm which medications are still necessary and which you can stop taking (if any). This may not be necessary if each doctor records you medications at each visit. In my case, they do and the doctor's assistant does this and he reviews it.

If a certain medication is out of your budget, ask your health care provider whether there is a cheaper, and still effective, alternative. It is important to remember that there is not a stupid question pertaining to medications. Consider asking questions of your pharmacist if your doctor does not answer the question.

Carb Ranges for Meal Planning

The range of carbohydrates for the different categories, very low carb, low carb, moderate carb, high carb, and extreme high carb varies greatly and there is no consensus or official ranges. Still some blog authors have done their research and spelled out ranges to consider.

Jimmy Moore who blogs at Livin La Vida Low-Carb has the following to say, “What is a low-carb diet? That seems like such an elementary question to ask, especially to people who are already following Atkins, Protein Power, or any of the many other respected and proven carbohydrate-restricted nutritional approaches that have emerged over the years. And yet defining what “low-carb” means is an important distinction since there is debate over how low you should go and at what point carb intake is no longer considered low.

Organizing a virtual who’s who of low-carb diet research and practice, a review article published in the journal Nutrition and Metabolism last year attempted to come to a consensus on what constitutes a low-carb diet. You may recognize a few of the names featured on the expert panel shaping this definition: Dr. Richard Bernstein, Dr. Annika Dahlqvist, Dr. Richard Feinman, Uffe Ravnskov, Dr. Jeff Volek, Dr. Eric Westman, Dr. Jay Wortman and Dr. Mary Vernon, among many others. The collective wisdom of this group of highly-qualified experts came up with the following:

So, we have three distinct and practical terms and definitions to use now:

Low-carb ketogenic diet (LCKD): less than 50g carbs and 10% calories dailyLow-carb diet (LCD): 50-130g carbs daily and between 10-26% of caloriesModerate-carb diet (MCD): 130-225g carbs daily and between 26-45% of calories

This is the first time we’ve seen actual numbers and percentages applied to what defines a low-carb diet.”

Then I did some more searching and the blog Mark's Daily Apple on January 14, 2009 had a listing that I found interesting.

“300 or more grams/day - Danger Zone! Extreme high carb

Easy to reach with the “normal” American diet (cereals, pasta, rice, bread, waffles, pancakes, muffins, soft drinks, packaged snacks, sweets, desserts). High risk of excess fat storage, inflammation, increased disease markers including Metabolic Syndrome or diabetes. Sharp reduction of grains and other processed carbs is critical unless you are on the “chronic cardio” treadmill (which has its own major drawbacks).

150-300 grams/day – Steady, Insidious Weight Gain High carb

Continued higher insulin-stimulating effect prevents efficient fat burning and contributes to widespread chronic disease conditions. This range – irresponsibly recommended by the USDA and other diet authorities – can lead to the statistical US average gain of 1.5 pounds of fat per year for forty years.

100-150 grams/day – Primal Blueprint Maintenance Range Moderate carb

This range based on body weight and activity level. When combined with Primal exercises, allows for genetically optimal fat burning and muscle development. Range derived from Grok’s (ancestors’) example of enjoying abundant vegetables and fruits and avoiding grains and sugars.

50-100 grams/day – Primal Sweet Spot for Effortless Weight Loss Low carb

Minimizes insulin production and ramps up fat metabolism. By meeting average daily protein requirements (.7 – 1 gram per pound of lean bodyweight formula), eating nutritious vegetables and fruits (easy to stay in 50-100 gram range, even with generous servings), and staying satisfied with delicious high fat foods (meat, fish, eggs, nuts, seeds), you can lose one to two pounds of body fat per week and then keep it off forever by eating in the maintenance range.

0-50 grams/day – Ketosis and Accelerated Fat Burning Very low carb

Acceptable for a day or two of Intermittent Fasting towards aggressive weight loss efforts, provided adequate protein, fat and supplements are consumed otherwise. May be ideal for many diabetics. Not necessarily recommended as a long-term practice for otherwise healthy people due to resultant deprivation of high nutrient value vegetables and fruits.”

I quoted much of the above because I felt they were important and something we could all benefit by learning from these two individuals. I am especially appreciative of the information from Mark's Daily Apple.

I had my own thoughts for ranges, but I can live with the thoughts of the second blog.

The explanations (not in red) are my classifications of the carbohydrate ranges.

What Are the Old Curmudgeons Up to Today?

A curmudgeon generally refers to an elderly person that is bad-tempered, difficult, and cantankerous. I can be one of these people at times, especially when I am in the company of another person with diabetes that is doing little to manage his/her diabetes.

In general, there are at least two types of curmudgeons. There are those that have life's experiences that they are being difficult about, or those that have knowledge and/or wisdom that they are imparting to the rest of us. Whether the person is bad-tempered or cantankerous will often depend on the listener and if they can agree or find a way to sooth the feelings of the elder person.

I don't enjoy being bad-tempered or difficult, but there are times when this is the only way I can capture the attention of the person not managing his or her diabetes.

Now I am doing something that I don't like doing or very often, but feel that what I have been reading and learning over the last few years is very indicative of what will happen over the next few years. Yes, I am taking a chance and a risky one, but someone needs to make people aware that this is not that far away.

#1. Under the current medical laws, people with diabetes reaching a certain age (mostly 65 and up) will no longer be able to obtain organ transplants of any kind even if they have a proven record of excellent diabetes management.

#2. People with HbA1c levels above certain levels will no longer be able to obtain certain medications to manage their diabetes. Equipment to help them manage diabetes will not be available. The CMS is also making it more difficult to obtain reliable testing supplies for diabetes.

#3. Many people with certain diseases and cancer will not be able to receive treatment and will be denied lifesaving medications or treatments. They will be given pain medications and allowed to die.

#4. Many hospitals will refuse treatments to people that don't have living wills and do not resuscitate orders on file. A few hospitals are already enforcing this.  More hospitals will be practicing medical blackmail when parents of children ask to get a second opinion.  This blackmail involves calling in childrens' social services and taking control of the children.  Increasingly, hospitals are accusing caretakers of medical child abuse, also known as Munchausen Syndrome by Proxy, in order to seize control of a child’s medical fate. 

Doctors at the Boston Children’s did just that in 2013.  Read more about how hospitals are treating our children here.

#5. More people will file bankruptcies under the current Affordable Care Act than ever before in all generations.

#6. More money will be wasted on studies of no clinical value than is already being wasted. More people will want to prove their values and will spend the money to do just that. Valuable studies of clinical value will cease to happen as Big Pharma, Big Food, Big Chemical, and Big Agriculture are going to find their profits shrinking in the face of Big Government forcing costs down.

#7. The war on patients will make patients' lives more difficult and make #5 accelerate at an even faster pace.

Life for the elderly will be returned to the days when they were dependent on the handouts from others. For those unable to afford medical care and the necessities of daily living, life will become a battle unlike this country has ever seen.

Although this link is not about any one disease in particular, it is still interesting and has a powerful message.

Dr. Kendrick Declares Scientific Debate Essential

If you have been reading my blogs of late, you have seen me criticize some of the researchers. Some have deserved it, but others are openly not thinking and applying their knowledge for research to benefit clinical research which will be needed for the fight against disease. Dr. Kendrick makes a discussion on valuable points necessary.

I will quote some of what Dr. Kendrick says. “Debate in science is essential. You would hope it were the very lifeblood of progress. One would also hope that researchers could disagree with each other in frank and open debate. But it has become increasingly obvious to me that if you criticise the experts in medical research you can expect a very rough ride indeed. You certainly risk being stomped into silence.”

“I have witnessed this quite a lot recently, and have found that the ‘stomping’ game is very simple. If a critic of an area of mainstream medicine seems to be gaining some traction with the public, they are very rapidly accused of ‘killing patients’ by various professors a.k.a. ‘experts.’”

“Sadly, it has become an article of faith that ‘experts’ cannot be argued with. For they have attained the status of demi-gods.”

“Canadian-based researcher, David Sackett, said that he would “never again lecture, write, or referee anything to do with evidence based clinical practice.” Sackett is not doing this because he has ceased to believe in evidence based clinical practice but, as the BMJ comments, because he is worried about the power of experts in stifling new ideas and wants the retirement of experts to be made compulsory.”

I find the last part of the last paragraph to be in line with my thinking as a patient of type 2 diabetes – (Sackett) “is worried about the power of experts in stifling new ideas and wants the retirement of experts to be made compulsory.” How true this is and many of the 'experts' abuse their position to prevent evidence based scientific research. We find this in nutrition research, especially with the fat argument of Ancel Keys, who started the demonization of saturated fat. This study was, however, fatally flawed. This last information on Ancel Keys is from David Mendosa's blog here.

“Sackett claims that the prestige of experts (including himself) gives their opinions far greater persuasive power than they deserve on scientific grounds alone.” Whether through deference, fear, or respect, others tend not to challenge them, and progress towards the truth is impaired in the presence of an expert,” he writes.”

Rather than quote more from Dr. Kendrick, I would urge you to read his blog and follow his explanations. Then you will be able to understand why 'experts' are not always to be followed when they prevent open and honest scientific debate.

One more disclosure needs to be discussed. The media of today, science writers, journalists, are all afraid of the experts and quote them as being “the expert.” Instead of asking hard questions about why the person is considered an expert, they worship the experts. All sorts of apologies happen the media uses something that the expert does not approve.

Insulin Type 2 Patients Over 80 Have More Hypoglycemia

You will have to excuse me if I seem to be on a rant. Headlines lately have been so misleading and down right sensationalized that I have thought to bypass the articles. In reading the articles further, I felt that rather than pass them by, maybe there were some lessons to be learned.

The headline for this one is rather tame, but still somewhat misleading - Hypoglycemia in Insulin-Treated Patients. The summary to get your attention says the following - “The elderly with diabetes now experience episodes of hypoglycemia more frequently than hyperglycemia.” Oh really! Since this is Dr. Andrew Geller, a medical officer at the Centers for Disease Control and Prevention (CDC), I had hoped to get some facts and perspective. Instead, it is mainly misinformation and highly misleading.

I admit that when I am told that this is an expert commentary, I become skeptical about the accuracy of what I am being told. Most of the time information to inform readers and explain what they are talking about is missing. General terms of severe hypoglycemia bother me. Does this mean anything below 50 mg/dl or a number below that? I will also think when they are talking hyperglycemia they are talking blood glucose levels above 180 mg/dl. Yet we are not informed and cannot therefore draw any accurate comparisons.

The only statement of substance comes in the fourth paragraph when Dr. Geller states, “Insulin-treated patients who are 80 years of age or older are more than twice as likely to go to the emergency department as patients between 45 and 64 years old. They were also 5 times more likely to be hospitalized. These findings underscore the importance of taking the risks for hypoglycemia into account when making decisions to prescribe or intensify insulin, especially among older adults.”

The expert missed an opportunity, in my opinion, to alert other doctors about checking for memory problems. Instead he just regurgitated what was supposedly reported about meal planning saying, “Meal planning is a well-recognized component of diabetes education. However, among the emergency department visits involving medication errors, a meal-related issue was the most common problem that brought patients to the emergency department.”

In the example he used of the patient injecting the short or rapid acting insulin and then forgetting to eat the meal timely, hypoglycemia caused them to go the emergency department. To me this means that memory problems should be investigated, but there is no mention of people over 80 often having these problems. Even distractions could be a problem, but instead meal planning is the only culprit.

This is what the expert says, “It's essential for diabetes patient education to continue emphasizing the importance of meal planning, and encourage patients to pay close attention to the insulin product that they administer.” Even I have made that mistake, but not often and normally (only three times in ten years) I inject the rapid acting too close to the injection site for the long acting. This causes the long acting to be converted to short acting and hypoglycemia did result. Fortunately, I recognized the problem as soon as I took the syringe out. Therefore, I had glucose tablets at the ready and started testing in 30 minutes. I tested about every 15 minutes and took glucose tablets accordingly until my glucose levels were at the proper level.

Granted the Medscape article was written for doctors, but as a patient, I feel that the information given was fair, but missed several points and alerts that should have been covered.

Type 2 Diabetes Turmoil in Treatments

Yes, there is a lot of turmoil in the type 2 medications treatment arena because of poor science like this article. The headline of the article in Medscape is “Deaths Higher When Insulin Is Second-Line Treatment for Type 2 Diabetes.” The title for the WebMD article is “Insulin-Metformin Combo Tied to Poorer Survival” and subtitled, “Other experts dispute the study's conclusions.” This blogger, Jenny Ruhl has a better title - “Why Insulin Plus Metformin May be Associated with Higher Mortality.”

I find it very hard to believe that Medscape and WebMD are related companies because of the two varied titles. I can believe the Medscape article headline is true because too often insulin in the second or even up to the fourth line of treatment. In reality, insulin should be the first line of treatment. David Mendosa writes an excellent blog here about the benefits of insulin being a short first-line of treatment.

I am in disagreement with the lead author of the research, Christianne L. Roumie, MD, associate professor of internal medicine and pediatrics at Vanderbilt University, Nashville, Tennessee. She states it is better to use two oral medications before progressing to insulin use for people with type 2 diabetes. The preferred second drug is a sulfonylurea and her study claims that this combination causes less death than metformin and insulin combination.

What she seems to forget is that the sulfonylureas have come under investigation as causing cardiovascular deaths as well. Read my blog about this here.

Most family doctors or primary care doctors know so little about dosing insulin that they stack oral medication on top of oral medication until insulin is required. They also attempt to keep type 2 patients on oral medications until it is too late for insulin to really help the way it should have if used earlier. In addition, general practitioners are afraid of hypoglycemia and this also drives them to want to keep type 2 patients on oral medications.

Then the author all but negates the study by making the following statement. “She also cautioned that findings from work such as this can create uncertainty. The complex statistical methods needed to overcome the various sources of bias and confounding that are inherent in observational research and the fact that this is a comparative-effectiveness study make it difficult for clinicians to interpret the data, she noted. "Given these caveats, many clinicians will probably refrain from making practice changes based on this study."”

Insulin Analogs, Worth the Cost?

This is another researcher looking for publicity and her 15 minutes of fame. Kasia J. Lipska, MD, an endocrinologist from the Yale School of Medicine, New Haven, Connecticut, will be presenting this research as a poster at the meeting of the American Diabetes Association (ADA) 2014 Scientific Sessions in San Francisco.

“Dr. Lipska and colleagues conducted a retrospective analysis of figures from the Optum Labs Data Warehouse, an administrative claims database of privately insured enrollees from throughout the United States. Adults aged 18 years or older with type 2 diabetes and at least 2 years of continuous plan enrollment between January 2000 and September 2010 were included. There were 123,486 enrollees who filled at least 1 prescription for insulin, with the proportion doing so rising from 9.7% in 2000 to 15.1% in 2010.”

“Dr. Lipska cautioned these findings from private health insurance records may not reflect publicly insured populations. For example, analog-insulin use is lower in the Veterans' Administration system, which has a national formulary scheme.”

“The data also couldn't capture less severe hypoglycemia that did not result in an emergency-department visit or hospital admission, she noted.”

"We are absolutely not suggesting that people stop using insulin analogs. But we hope these findings provoke a discussion about the value of healthcare for the overall population of type 2 diabetes patients."

I am very happy that there were comments and most agreed with my feelings. This is not a study, but an observational analysis of very diverse data and many missing pieces of information. And with funds from the Centers for Medicare & Medicaid Services and the National Institutes of Health, I suspect some false motives in the method of research.

Is the CMS trying to find ways to deny people on Medicare and Medicaid the use of certain insulins? I suspect this!  I just hope I am wrong.