Doctors Ignore Potentially Damaging Drug Side Effects

Most doctors get their information about drugs from the pharmaceutical companies that sell them. There companies have a long record of suppressing information about damaging side effects of these drugs. Periodically, one of these drugs will kill or injure enough people that it comes to the attention of the FDA and the media. This was the case with the SSRIs that cause suicidal behavior in many children and Rezulin which caused liver failure in some diabetics.

I've been saying this for years, but a brand new study brought to my attention by the ever-vigilant Susan from alt.support.diabetes documents how true it is.

This study of a group of patients prescribed a statin drug found that "Eighty-seven percent of patients reportedly spoke to their physician about the possible connection between statin use and their symptom....Physicians were reportedly more likely to deny than affirm the possibility of a connection. Rejection of a possible connection was reported to occur even for symptoms with strong literature support for a drug connection, and even in patients for whom the symptom met presumptive literature-based criteria for probable or definite drug-adverse effect causality.

In plain English, even when a patient had a dangerous symptom that was flagged in the drug's prescribing information, doctors usually ignored it!

The article also points out that because they appear to believe drugs don't have side effects most doctors are not reporting NEW side effects to the FDA, even when patients have them.

Physician Response to Patient Reports of Adverse Drug Effects: Implications For Patient-Targeted Adverse Effect Surveillance.
Golomb, Beatrice A 1 2; McGraw, John J 1 3; Evans, Marcella A 1; Dimsdale, Joel E 4

Drug Safety. 30(8):669-675, 2007.

Side Effect Warnings Don't Distinguish the Trivial from the Severe

This may be one reason doctors ignore all side effects. Also the prescribing information may list a symptom like "tinnitus" but not indicate if the drug causes ringing in the ears that lasts an hour or two or high pitched squeals that will last a lifetime. I got tinnitus--a high pitched ringing in my ears from taking a drug called Clinoril. It turns out that tinnitus is a side effect that occurs with 2% of all people who take this drug, but my doctor responded to my early reports of ringing ears by telling me to take half the dose. I did, once, and my ears have been ringing ever since--for 10 years.

Because the FDA doesn't separate out serious side effects from minor ones, almost any drug you see will have a list of thirty or forty side effects listed. Because these include "headache, stomach ache, nervousness, back pain" and a lot of other symptoms doctors usually believe are "all in your head," doctors ignore the serious side effects which also appear in this list.

My goal here is to warn you about some of the drugs that you are likely to be prescribed and some of the dangerous side effects that you should be aware of. In addition, before you take any drug, download the Prescribing Information from the web--you can find it with Google by searching on the drug name and the words "prescribing information." Scroll to the "contraindications" section of the prescribing information to read warnings about who should not take the drug. Then read through the "adverse effects" section.

Doing this before you take a new medication can save you from a world of pain!

Some Commonly Prescribed Drugs that Can Hurt You

In the section below I've flagged a couple of drugs that are commonly prescribed to people with diabetes. Many people take them with no problems, other people develop the serious side effects listed. If you believe you are suffering one of these side effects, contact your doctor. If you are brushed off and told not to worry with no other reason given, it's time to look for a better doctor.

Statins

Statins are very expensive drugs used to lower LDL cholesterol whose manufacturers invest heavily in research meant to prove that everyone on the planet should take them for the rest of their lives--especially people with diabetes. Whether or not this is true is still subject to debate, but that isn't the topic here.

The issue here is that statins have serious, even fatal, side effects that many doctors ignore.

Muscle Damage

The best known dangerous side effect of the statins is called "Rhabdomyolysis." What that medical mouthful means in English is "breakdown of muscle fibers." As these fibers break down, they release by-products that are toxic to the kidneys. If enough muscle breaks down, you can die.

Most doctors know about this side effect, but they often fail to warn patients about it. As a results, patients on statins may start experiencing muscle pains and weakness while having no idea that this is a symptom of this dangerous side effect.

A study that highlights some factors that make the dangerous breakdown of muscle with statins more likely found,

"The risk of myopathy is increased by: the use of high doses of statins, concurrent use of fibrates, concurrent use of hepatic cytochrome P450 inhibitors, acute viral infections, major trauma, surgery, hypothyroidism and other conditions."

Statin-associated myopathy. Hamilton-Craig I.Med J Aust. 2001 Nov 5;175(9):486-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11758079&query_hl=1&itool=pubmed_docsum

Note that hypothyroidism, (low thyroid) is common among people with Type 2 diabetes.

This study also concludes:
"Statin-associated myopathy should be suspected when a statin-treated patient complains of unexplained muscle pain, tenderness or weakness. Statin therapy should be stopped in cases of suspected myopathy, and serum creatine kinase levels should be checked and monitored. No specific therapies other than statin withdrawal and supportive measures for rhabdomyolysis are currently available."

So if you start experiencing worsening muscle pains while on a statin drug contact your doctor immediately and don't let them brush this side effect off as unimportant. The heart is a muscle, too!

There are other drugs you can take to lower cholesterol besides statins. Also, as we've documented in the A1c predicts heart attack page for a person who has not had a previous heart attack, the evidence suggests that the Framingham ratios rather than total or LDL cholesterol levels are what predicts heart attack. There is now a growing body of evidence that lower carb diets lower triglycerides and raise HDL which greatly improve these predictive Framingham ratios.

http://jama.ama-assn.org/cgi/content/full/289/13/1681

Rhabdomyolysis with statins
http://www.jr2.ox.ac.uk/bandolier/band131/b131-2.html



A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia. A Randomized, Controlled Trial. W.S. Yancy Jr., M.K. Olsen, J.R. Guyton, R.P. Bakst, and E.C. Westman. Annals of Internal Medicine May 18, 2004, volume 140, pages 769-777. T
http://www.annals.org/cgi/content/summary/140/10/769

Statin-Associated Myopathy.Paul D. Thompson, MD; Priscilla Clarkson, PhD; Richard H. Karas, MD, PhD. JAMA. 2003;289:1681-1690.

Brain Damage and Permanent Memory Loss

There are both anecdotal reports and research studies that show that statins can cause permanent damage to the memory and other cognitive symptoms.

For an excellent review of the research findings about these dangerous side effects which though written with a focus on the elderly cover apply to all patients taking statins, read

Statin Adverse Effects: Implications for the Elderly by Beatrice A. Golomb, M.D., Ph.D.


http://www.geriatrictimes.com/g040618.html

Other recently published studies about cognitive problems caused by statin drugs include:

King DS, Wilburn AJ, Wofford MR, Harrell TK, Lindley BJ, Jones DW. Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy. 2003 Dec;23(12):1663-7.



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14695047

Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy. 2003 Jul;23(7):871-80.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12885101

Lowered LDL Correlates with More Blood Cancers and Sepsis

A study reporting a new and troubling side effect of lowering LDL came out in November of 2007. It looked at a group of 203 patients and found that in this group "Each 1 mg/dl increase in LDL was associated with a relative reduction of 2.4% in the odds of hematological cancer (OR 0.976, 95% CI 0.956–0.997, p = 0.026). Low LDL levels also increased the odds of fever and sepsis." It is not clear whether this effect stems from the lack of LDL or is a side effect of drugs used to lower LDL.

Low Serum LDL Cholesterol Levels and the Risk of Fever, Sepsis, and Malignancy.
Renana Shor, Julio Wainstein, David Oz, Mona Boaz, Zipora Matas, Asora Fux and Aaron Halabe1. Annals of Clinical & Laboratory Science 37:343-348 (2007)

http://www.annclinlabsci.org/cgi/content/abstract/37/4/343


A Letter from Drs. Mark R. Goldstein, Luca Mascitelli and Francesca Pezzetta that published in the journal Current Oncology in April of 2008 argues that the statins themselves may be the cause for the increase of cancers, particular in older people with compromised immune systems. They explain, "Statins increase the number of regulatory T cells (Tregs) in vivo by inducing the transcription factor forkhead box P3 2. Although that increase may be beneficial in stabilizing atherosclerotic plaque by reducing the effector T-cell response within the atheroma, it
might impair both the innate and adaptive host antitumour immune responses. Not surprisingly, the numberof Tregs present in many solid tumours correlate inversely with patient survival."

Statins Increase Insulin Resistance

And if all this weren't enough, a study published in the journal Diabetes in January 2008 found that as the title says, "Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patient." Translated into English, this means that Zocor decreases the hormone, Adiponectin, that keeps people from gaining weight and makes people who take it more insulin resistant. Can the epidemic of misprescribing of Statins have something to do with the huge growth in obesity and blood sugar disorders?

You'll find the Statin/Insulin Resistance study here:

http://care.diabetesjournals.org/cgi/content/abstract/31/4/776

Anecdotal Information About Statin Problems

Visit the Talking Statins web site for more information about patient reports of serious cognitive and physiological side effects, many permanent, ascribed to taking statin drugs. There's also a petition you can sign requesting WHO to undertake an impartial study of the safety of these drugs.

Zetia/Vytorin Found to Lower Cholesterol and Increase Speed of Plaque Growth

In the last months of 2007 the media began to report that Merck and Schering-Plough had been delaying the publication of a major research study which had been intended to explore whether Zetia had any effect on cardiovascular outcomes. Most seriously, it was found that the drug companies had tried to alter the endpoints used in the study--in other words, because the way of analyzing data originally decided upon did not appear to show that the drug was effective in preventing cardiovascular events (i.e. stroke and heart attack), these drug companies wanted to publish only results that looked at some other measurement.

Then in December of 2007, the New York Times resported that the drug companies had also suppressed the publication of other studies that showed that taking Zetia along with a statin raised the risk of liver damage. Since Vytorin is Zetia combined with a statin, this is significant.

http://www.nytimes.com/2007/12/21/business/21drug.html?_r=1&ref=health
Data About Zetia Risks Was Not Fully Revealed.
Alex Berenson. New York Times. Dec 21, 2007.

The New York Times also reported "... in Australia and Canada, regulators have been more cautious. Since 2005, they have issued a series of warnings about Zetia’s potential to cause hepatitis, pancreatitis and depression — warnings that have largely gone unnoticed in the United States."


On January 14, 2008 the New York Times reported that the drug companies finally released their big study on Zetia/Vytorin. Here is what the report stated: "While Zetia lowers cholesterol by 15 to 20 percent in most patients, no trial has ever shown that it can reduce heart attacks and strokes — or even that it reduces the growth of the fatty plaques in arteries that can cause heart problems.

"This trial was designed to show that Zetia could reduce the growth of those plaques.Instead, the plaques actually grew almost twice as fast in patients taking Zetia along with Zocor than in those taking Zocor alone."

In short, not only did the drug not prevent heart disease, it appears to make it worse!

So now we know why they tried to suppress the publication of the study and "redefine" the measured endpoint--which included the thickness of plaque.

There is now no doubt that this is a dangerous drug that no person with diabetes should consider taking. Watch out of drug company spin--Pfizer is still selling Celebrex, despite the proofs that it causes heart attacks. Merck will undoubtedly come up with some way to convince you this drug is safe, but it isn't!

http://www.nytimes.com/2008/01/14/business/14cnd-drug.html
Cholesterol Drug has No Benefit in Trial
Alex Berenson. New York Times. Jan 14, 2008.

Bottom line: While Zetia does apparently lower LDL cholesterol it looks like this lowering does not prevent heart attack. That will come as no surprise to those of you who have read the Why LDL does Not Predict Heart Attack section on my "A1c and Heart Attack" page. Now that it looks like these expensive new drugs can also cause serious, if not fatal side effects, and that their makers have put considerable effort into suppressing information about their lack of effectiveness and their ability to cause serious harm, there is no reason to take either drug.

ACE Inhibitors

ACE inhibitors like lisinopril and ramipril control blood pressure by lowering a substance, angiotensin, which causes blood vessels to contract. They have also been shown to have a protective effect on the kidneys of people with diabetes. These are excellent drugs for people with diabetes, except, that they can have some problem side effects you should know about if you are taking them.

Cough

The most significant side effect with ACE inhibitors is a relentless cough. If you develop such a cough while taking these drugs, tell your doctor and ask to be switched to a newer drug in the ARB family. These ARB drugs, which include Cozaar, Diovan, and Avapro work in a way that is similar to ACE inhibitors but they do not cause the troubling side effects.

There are other rarer and much more dangerous side effects of ACE inhibitors about which doctors may be ignorant.

Birth Defects

If there is any chance you might get pregnant you cannot take ACE inhibitors or ARBs. They are known to cause birth defects.

Kidney Failure

While these drugs preserve the function of the kidney in people with diabetes whose kidneys are normal, they can be very dangerous in people whose kidneys are severely damaged. If you have diabetes and haven't had your kidney function tested, talk to your doctor about getting kidney function testing before you start taking these drugs.

Allergic Reactions

Facial swelling is a serious side effect that these drugs can cause. It is supposed to be rare, but it happened to me. If it happens to you, don't continue taking the drug! Swelling in the intestines is another possible allergic side effect. It's symptom is stomach pain.

Potassium Imbalance

Many doctors who prescribe these drugs do not remember to tell their patients that they cause the body to hold on to potassium. If you take potassium supplements along with these drugs or eat a lot of foods that contain a lot of potassium, there is the potential to develop a life-threatening electrolyte imbalance which can cause your heart to beat irregularly.

Do NOT take potassium supplements while taking ACE inhibitors or ARB drugs.

Kidney Failure with a Drug for Colonoscopy Prep

It has recently been discovered that a common drug given to clean the bowel before a colonoscopy can, in some tragic situations, combine with an ACE inhibitor or ARB to produce permanent kidney failure resulting in dialysis.

If you are going to have colonoscopy, do not take an oral sodium phosphate drug beforehand and make sure your doctor knows you are on one of these drugs.

Acute Phosphate Nephropathy following Oral Sodium Phosphate Bowel Purgative: An Underrecognized Cause of Chronic Renal Failure

Glen S. Markowitz, M. Barry Stokes, Jai Radhakrishnan and Vivette D. D’Agati


http://jasn.asnjournals.org/cgi/content/abstract/16/11/3389

For a good summary of adverse reactions possible with one popular ACE inhibitor, lisinopril, see:

http://www.healthscout.com/rxdetail/68/22/3/main.html

Neurontin

Suicidal Thought and Action

This drug was approved only for the treatment of seizures. However since few people have seizures the manufacturer indulged in a huge and illegal campaign to get doctors to prescribe this drug for conditions it has not been tested for. The drug company that makes Neurontin pleaded guilty to illegally marketing the drug. However, their marketing worked, and doctors continue to prescribe Neurontin for many off-label uses including the pain associated with diabetic neuropathy.

Now a new rash of lawsuits is claiming that Neurontin causes suicidal thoughts and behavior and that the company suppressed this information.

You can read about this in more detail here:

http://www.ahrp.org/infomail/04/07/26a.php

The FDA finally issued a warning about the increased likelihood of Neurontin and other epilepsy drugs in January of 2008.

U.S. warns of suicidal actions with epilepsy drugs - Reuters news item Feb 1, 2008

If you are taking Neurontin for neuropathy warn your family that suicidal thought and action may be a possible side effect and do not continue to take it if you see any signs of changes in your emotional status.

Zyprexa

Zyprexa Causes Severe, Permanent, Diabetes

After years of ignoring the data, the manufacturers of Zyprexa and Clozaril have finally admitted, under pressure, that these drugs can cause irreversible and sometimes fatal type 2 diabetes in people who take them. If you already have type 2 diabetes, these drugs could completely destroy your control.

If you have a serious psychosis that has not responded to any other medication, this may be a risk you have to accept. However, many patients have been prescribed these extremely powerful drugs for milder mental conditions that are known to respond to other, less harmful drugs.

If you have diabetes or a family history of diabetes don't let a doctor give you Zyprexa until you have exhausted all other possibilities. Many doctors still do not know or understand the impact of the fact that a brief course of Zyprexa could be a life sentence to diabetes.

Before you take any drug in this family, the so-called atypical antipsychotics, do a Google search for the latest information about its potential to cause diabetes. New information about the damage caused by these drugs appears almost every month.

Here is the FDA's warning letter to doctors about Zyprexa:

ttp://www.fda.gov/medwatch/SAFETY/2004/zyprexa.htm

Beta Blockers

Increase incidence of Type 2 Diabetes and Stroke and Don't Prevent Heart Attacks or Death

Thanks to Alan S for flagging this metastudy of almost 95,000 patients taking beta blockers for twelve or more years.

http://lib.bioinfo.pl/pmid:17920367
A Meta-Analysis of 94,492 Patients With Hypertension Treated With Beta Blockers to Determine the Risk of New-Onset Diabetes Mellitus. Sripal Bangalore , Sanobar Parkar , Ehud Grossman , Franz H Messerli. Am J Cardiol. 2007 Oct 15;100 (8):1254-1262 17920367

This study found that "Beta-blocker therapy resulted in a 22% increased risk for new-onset DM." The study which looked at results twelve years after patients started the drug also concluded that "beta blockers resulted in a 15% increased risk for stroke, with no benefit for the end point of death or myocardial infarction." In plain English this means that beta blockers may cause or worsen Type 2 diabetes while failing to prevent heart attacks or death and possibly causing stroke. Sounds like a great drug, eh?

Beta blockers are prescribed mostly for high blood pressure and their generic names usually end in "lol. They include Atenolol (Tenormin), Metoprolol (Lopressor, Toprol-XL), Propranolol (Inderal, Inderal LA). If a doctor or cardiologist prescribes one of these drugs to you, demand an explanation why they chose that kind of drug with its long list of troubling side effects instead of one of the blood pressure drugs that have been shown to protect the kidneys and possibly lessen insulin resistance. These alternative blood pressure drugs include ACE inhibitors like Lisinopril and ARBs like Diovan.

Reading this, I have to wonder whether the fact that these drugs were prescribed as front line drugs for high blood pressure for the past several decades might have something to do with the emergence of the so-called "Diabetes epidemic."

Cortisones - Prednisone, Dexamethasone, etc.

These powerful drugs can be lifesaving for some conditions. They can also provide relief from serious joint pain and perhaps help people with Multiple Sclerosis. It is well known that they raise blood sugar while you take them in pill or injection form. (Topical cortisone creams are usually not a problem.)

What many doctors don't seem to understand is that these drugs can also permanently damage blood sugar control. Several people have reported online and in emails to me that they were able to control their type 2 diabetes with diet and exercise alone, but that after taking cortisone shots for back injuries their blood sugar control worsened to where it could only be controlled with the help of drugs.

Bottom line: Treat cortisone drugs with great respect and use them only if you have a serious condition that requires them. If you are prescribed cortisone for frozen shoulder, be aware that that cortisone may give temporary pain relief but it does not shorten the time it takes for the frozen shoulder to heal. There are even tendon problems where cortisone can worsen rather than improve the problem. Once the inflammatory phase of a frozen shoulder is over, acupuncture or acupressure massage can be very helpful in freeing up the constricted joint.

Common Over-the-Counter Pain Killers

There is increasing evidence that both acetaminophen (Tylenol)and NSAIDS including Ibuprofen and Naproxen (Advil, Motrin, Anaprox)slowly destroy the kidney. The relationship is related to the lifetime dose. This means every little bit of these drugs adds up, and over a life time taking even one pill a day for only a month or two a year can end up causing significant kidney damage. And these findings are for everyone, not just people with diabetes!

A new study published in Archives of Internal Medicine found new evidence of this effect when if discovered that men "who took acetaminophen six or seven days a week had a 34% higher risk of hypertension. Those who took NSAIDs six or seven days a week had a 38% higher risk and those who took aspirin six or seven days a week had a 26% higher risk."

Hypertension is often the very first sign of kidney disease.

Does this mean you should never take any painkillers? Not really. But it does mean that you shouldn't pop "vitamin I" (the hip nickname for Ibuprofen) every time you have a minor muscle tenderness after exercise. If you have serious pain and must take one of these pills, experiment to find what the lowest dose is that is effective and if possible avoid the double dose "extra strength" version.

Reported in 3/7/07 Diabetes in Control Newsletter


Risk of Kidney Failure Associated with the Use of Acetaminophen, Aspirin, and Nonsteroidal Antiinflammatory Drugs.
Thomas V. Perneger, Paul K. Whelton, and Michael J. Klag

SSRI Antidepressants

Evidence is accumulating that antidepressants cause diabetes. For years, the companies that make these drugs have tried to suggest that people with diabetes are more depressive than the population at large, to suggest that the diabetes seen in the population taking these drugs preceded their use.

But a study published in Diabetes Care in March, 2008 tested this hypothesis by examining the huge population in the DPPT trial (the one that examined whether metformin could prevent diabetes, among other things) and found that "strong and statistically significant association between antidepressant use and diabetes risk in the PLB and ILS arms was not accounted for by measured confounders or mediators." In English, this means that depression previous to taking the drug did not correlate to a heightened risk of getting diabetes, but taking an antidepressant did.

The study also found that people taking metformin and SSRIs were not as prone to develop diabetes, but this has to be interpreted with the knowledge that after the DPPT was over, patients who went off metformin developed diabetes at an alarming rate. The DPPT and metformin is discussed further HERE.

This is not the first time that SSRIs have been found to cause diabetes, but it is by far the largest study to look at the issue.

Elevated Depression Symptoms, Antidepressant Medicine Use, and Risk of Developing Diabetes During the Diabetes Prevention Program.
Richard R. Rubin et. al, Diabetes Care 31:420-426, 2008