Editor Emeritus on June 29th, 2011

The Vitamin D Council, a nonprofit educational corporation, is set to file a complaint to the Attorney General against the Food and Drug Administration (FDA) regarding policies that disparately afflict African Americans. The Vitamin D Council argues that through a combination of mandated and encouraged practices, the FDA depends upon milk to deliver virtually all supplemental dietary vitamin D to Americans. The FDA knows African Americans consume little milk, particularly relative to Caucasian Americans.

In effort to strengthen the complaint, the Vitamin D Council launched a petition today, seeking backing from citizens all across the country. The petition can be found at: www.change.org/petitions/back-health-equality-complaint-against-fda-2

Vitamin D is a hormone activated by sunlight. Due to their darker skin, African Americans require six to ten times the amount of sun exposure Caucasian Americans do to activate the same amount of vitamin D. In consequence, African Americans are much more likely to be deficient in vitamin D.

 “All Americans, regardless of the amount of melanin pigment in their skin, deserve equal treatment under de facto FDA policies.” – John Cannell MD, Vitamin D Council Founder and Executive Director

The Vitamin D Council argues that the FDA, in effect, chooses to fortify a food that does not target a population who most need vitamin D. The Vitamin D Council calls upon the FDA to mandate and encourage fortifying foods that African Americans are more likely and able to consume. Says Vitamin D Council Executive Director, Dr. John J. Cannell, “All Americans, regardless of the amount of melanin pigment in their skin, deserve equal treatment under de facto FDA policies.”

Vitamin D deficiency has been linked to over one-hundred diseases and illnesses. Studies show that African Americans, as compared to other ethnic or racial groups, bear a greatly increased risk of suffering and dying from these same diseases, including heart disease, cancer, hypertension, and diabetes.

About the Vitamin D Council

Founded in 2003 on the conviction that people all over the world are needlessly suffering from vitamin D deficiency, the Vitamin D Council is a nonprofit tax-exempt 501(c)(3) educational corporation in the State of California. The Vitamin D Council’s mission is to end the worldwide epidemic of vitamin D deficiency by means of outreach and awareness, research, and political action.

For more information, visit www.vitamindcouncil.org.

The petition can be found at www.change.org/petitions/back-health-equality-complaint-against-fda-2

The Health Gazette strongly endorses the actions of the Vitamin D Council and encourages all Americans to sign the petition.

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Editor Emeritus on June 17th, 2011

The MedWatch May 2011 Safety Labeling Changes posting includes 47 products with safety labeling changes to the following sections: BOXED WARNINGS, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, PATIENT PACKAGE INSERT, and MEDICATION GUIDE.

The “Summary Page” found via the following link provides a listing of drug names and safety labeling sections revised:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm258300.htm

Clicking on a drug product name in the Summary View on the page found via the above link will take you to the “detailed view” page, which identifies safety labeling sections and subsections revised, along with a brief summary of new or modified safety information. You can check the list below to find any affected drugs that may be of particular interest to you.

The following drugs had modifications to the BOXED WARNINGS, CONTRAINDICATIONS and WARNINGS sections:

  • Aciphex (rabeprazole sodium) Delayed-Release Tablets
  • Afinitor (everolimus) Tablets
  • Aldactazide (spironolactone/hydrochlorothiazide) Tablets
  • Avandia (rosiglitazone maleate)
  • Avandamet (rosiglitazone maleate/metformin hydrochloride)
  • Avandaryl (rosiglitazone maleate/glimepiride) Tablets
  • Benicar HCT (olmesartan medoxomil/hydrochlorothiazide) Tablets
  • Biaxin Filmtab (clarithromycin tablets, USP) Biaxin XL Filmtab (clarithromycin extended-release tablets),Biaxin Granules (clarithromycin for oral suspension, USP)
  • Dexilant (dexlansoprazole) Delayed Release Capsules
  • Genotropin (somatropin [rDNA origin] for Injection
  • Humalog (insulin lispro [rDNA origin]) Injection
  • Imuran (azathioprine) Tablets and Injection
  • Levatol (penbutolol sulfate) Tablets
  • Micardis HCT (telmisartan/hydrochlorothiazide) Tablets
  • Norditropin Cartridges (somatropin [rDNA origin] injection)
  • Omeprazole / Sodium Bicarbonate / Magnesium Hydroxide Tablets
  • Prevacid(Lansoprazole) Delayed-Release Capsules
  • Prevacid SoluTab (Lansoprazole) Delayed-Release Orally Disintegrating Tablets
  • Prilosec (omeprazole) Delayed Release Capsules and Prilosec (omeprazole magnesium) For Delayed Release Oral Suspension
  • Protonix (pantoprazole sodium) For Delayed-Release Oral Suspension 40 mg and Protonix (pantoprazole sodium) Delayed-Release Tablets, Protonix I.V. (pantoprazole sodium) for Injection
  • Purinethol (mercaptopurine) Tablets
  • Seroquel (quetiapine fumarate) and Seroquel XR (quetiapine fumarate) Extended-ReleaseTablets
  • Sutent (sunitinib malate) Capsules
  • Teveten HCT (eprosartan mesylate/hydrochlorothiazide) Tablets
  • Uniretic (moexipril hydrochloride/hydrochlorothiazide)
  • Vimovo (naproxen/esomeprazole magnesium) Tablets
  • Zegerid (omeprazole/sodium bicarbonate) Capsules and Powder for Oral Suspension
  • Ziac (bisoprolol fumarate/hydrochlorothiazide) Tablets

If you are either prescribing or consuming any of the above you would be wise to read the detailed page of information about the changes.

You should avoid taking any drugs unless you absolutely have to take them. Do not be persuaded that you need drugs on the basis of pharmaceutical company advertising! Do not accept a prescription unless the prescriber provides you with a clear explanation of why you need it, how it works, what benefits you should notice, all of the known side-effects, what alternatives exist and what will happen if you decline the prescription.

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The FDA notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer).

The new safety information is based on FDA’s review of two large, randomized controlled trials––the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. Proscar, Avodart, and Jalyn are approved to improve symptoms of an enlarged prostate gland (benign prostatic hyperplasia or BPH). Proscar and Avodart are also approved to reduce the risk of urinary retention or surgery related to an enlarged prostate. Propecia is approved to treat male pattern hair loss.

The FDA recommends that prior to initiating therapy with 5-ARIs, doctors perform appropriate evaluation to rule out other urological conditions, including prostate cancer, that might mimic benign prostatic hyperplasia (BPH). See Drug Safety Communication for a Data Summary and additional information.

It seems the FDA knows something about common medical practice as their recommendation implies that doctors do not do this on a reliable basis or perhaps not at all. That is positively scary.

Healthcare professionals and patients are encouraged to report adverse events, side effects, or product quality problems related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

The most important differential (or other possible) diagnosis to eliminate when diagnosing BPH is prostate cancer. There is considerable irony at best in discovery of a link between serious prostate cancer and drugs such as Proscar, Avodart, and Jalyn which are approved to improve symptoms of BPH.

As for Propecia, a drug approved to treat male pattern hair loss, one has to wonder if the likelihood of developing serious prostate cancer will overcome the vanity that supports the market for this drug. This has always been a foolish drug, now it is foolhardy.

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Editor Emeritus on June 9th, 2011

FDA announces new safety recommendations for high-dose simvastatin due to Increased risk of muscle injury.

The U.S. Food and Drug Administration today is announcing safety label changes for the cholesterol-lowering medication simvastatin because the highest approved dose–80 milligram (mg)–has been associated with an elevated risk of muscle injury or myopathy, particularly during the first 12 months of use.

The agency is recommending that simvastatin 80 mg be used only in patients who have been taking this dose for 12 months or more and have not experienced any muscle toxicity. It should not be prescribed to new patients. There are also new contraindications and dose limitations for when simvastatin is taken with certain other medications.

Simvastatin is used together with diet and exercise to reduce the amount of “bad cholesterol” (low-density lipoprotein cholesterol or LDL-C) in the blood. In some studies high levels of LDL-C are linked to a higher risk of heart attack, stroke and cardiovascular death. In 2010, about 2.1 million patients in the United States were prescribed a product containing simvastatin 80 mg. This drug, like all statins, has been aggressively marketed and is grossly over prescribed.

“The FDA has completed its review of the safety of high-dose simvastatin and is making label changes to reduce the risk of statin-associated muscle injury,” said Eric Colman, M.D., deputy director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “We want to ensure that patients and health care professionals are aware of the new labeling changes to simvastatin, including the increased risk of myopathy when using the 80 mg dose of simvastatin.”

The changes to the label for simvastatin-containing medications are based on the FDA’s review of the results of the seven-year Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine clinical trial, other clinical trial data, and analyses of adverse events submitted to the FDA’s Adverse Event Reporting System. All showed that patients taking simvastatin 80 mg daily had an increased risk of muscle injury compared to patients taking lower doses of simvastatin or other statin drugs. The risk of muscle injury is highest during the first year of treatment with the 80 mg dose of simvastatin, is often the result of interactions with certain other medicines, and is frequently associated with a genetic predisposition for simvastatin-related muscle injury.

Simvastatin is sold under the brand-name Zocor and as a single-ingredient generic product. It is also sold in combination with ezetimibe as Vytorin and in combination with niacin as Simcor.

The FDA has revised the drug labels for simvastatin and Vytorin to include the new 80 mg dosing restrictions. The agency also revised the labels for simvastatin, Vytorin and Simcor to include new dosing recommendations when these drugs are used with certain medications that interact to increase the level of simvastatin in the body, which can increase the risk for myopathy. Patients who are unable to adequately lower their level of LDL-C on simvastatin 40 mg should not be given the higher 80 mg dose of simvastatin; instead, they should be placed on an alternative LDL-C-lowering treatment(s).

One school of thought is that claims over many years that raised cholesterol is responsible for increased risk of heart disease are fundamentally wrong or have been significantly overstated. There may actually be little or no real scientific basis for the use of anti-cholesterol drugs. All such drugs cause some unwanted side effects, many of them severe. Long term use of statins is a particular concern. Unfortunately pharmaceutical companies are brilliant marketers, study manipulators and enjoy plenty of political power. Combine these facts with prescriber ignorance, overwork, undue reliance on drug representatives for “ongoing education” and a number of intra-professional and general cultural forces and we have a recipe for increasing wealth for pharmaceutical investors while consumers’ real health outcomes decline.

Patients taking simvastatin 80 mg daily have an increased risk of myopathy compared to patients taking lower doses of this drug or other drugs in the same class. This risk appears to be higher during the first year of treatment, is often the result of interactions with certain medicines, and is frequently associated with a genetic predisposition toward simvastatin-related myopathy. Patients with myopathy generally have muscle pain, tenderness or weakness, and an elevation of a muscle enzyme in the blood (creatine kinase, or CK). The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure which can be fatal. Rhabdomyolysis is rare; hospitalized rhabdomyolysis occurs in 4.9 people out of every 100,000 people exposed to simvastatin for one full year (the average incidence for hospitalized rhabdomyolysis for atorvastatin, pravastatin, or simvastatin is 4.4 people out of every 100,000 people). (Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292:2585-90.)

The new changes to the drug labels for simvastatin-containing medicines are based on FDA’s review of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial and other data described in the Agency’s March 2010 Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury.

SEARCH was a seven-year, randomized, double-blind clinical trial comparing the efficacy and safety of simvastatin 80 mg to simvastatin 20 mg, with or without vitamin B12 and folate, in survivors of myocardial infarction.

At the end of the trial, the incidence of major vascular events was 25.7% in the 20-mg group versus 24.5% in the 80-mg group [RR=0.094, 95% CI (0.88, 1.01); p=0.10]. Due in part to greater use of off-study LDL-C lowering medication in the simvastatin 20 mg group versus the 80-mg group, the difference in mean levels of LDL-C between the two treatment groups was 13 mg/dL instead of the expected difference of 20 mg/dL. Nonetheless, the 6% reduction in relative risk for major vascular events observed in SEARCH is consistent with the 13 mg/dL lower level of LDL-C in the 80-mg group.

Fifty-two patients (0.9%) in the 80-mg group versus one patient (0.02%) in the 20-mg group developed myopathy (defined as unexplained muscle weakness or pain with a serum CK >10 times the upper limit of normal [ULN]). This was higher than the labeled risk (based on clinical trial data) of 0.53%. Twenty-two patients (0.4%) in the 80-mg group versus no patient in the 20-mg group developed rhabdomyolysis (defined as unexplained muscle weakness or pain with serum CK >40 times ULN). There were no fatalities related to rhabdomyolysis.

The risks for myopathy and rhabdomyolysis with simvastatin 80 mg were highest in the first 12 months of treatment, 5 per 1000 person-years and 2 per 1000 person-years, respectively, and decreased to 1 per 1000 person-years and 0.4 per 1000 person-years after that.

Older age and female sex both increased the risk of myopathy. In SEARCH, the risk of myopathy was approximately doubled in patients taking a calcium channel blocker, in particular diltiazem. Approximately 60% of the cases of myopathy were associated with a genetic variant which affects the coding of the transporter responsible for simvastatin uptake into the liver. This variant increases the plasma concentration of simvastatin, thus increasing the risk of myopathy.

The findings from the SEARCH trial are supported by analyses of the FDA’s Adverse Event Reporting System (AERS) database, which show that the level of reporting of fatal rhabdomyolysis associated with the 80-mg dose of simvastatin has been higher in comparison with lower doses of simvastatin or lower doses of most other statins. In addition, clinical trial data from other long-term statin trials show higher overall rates of myopathy and rhabdomyolysis in patients treated with simvastatin 80 mg versus lower doses of simvastatin or other statins.

For more information from the FDA:

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MedWatch Alert

ISSUE: FDA is aware of two newly published studies that evaluated the risk of venous thromboembolism (VTE) in women who use birth control pills that contain drospirenone.  The two recently published studies looked at whether there is a higher risk of blood clots in women taking birth control pills containing the progestin drospirenone when compared to similar women taking birth control pills containing a different progestin called levonorgestrel. These two new studies reported that there is a greater risk of VTE associated with birth control pills that contain drospirenone.  This risk is reported to be up to 2 to 3 times greater than the risk of VTE associated with using levonorgestrel-containing pills. Other studies have not reported an increase in risk. The FDA is currently evaluating the conflicting results from these studies and will look at all currently available information to fully assess the risks and benefits of drospirenone-containing birth control pills.  FDA will continue to communicate any new safety information to the public as it becomes available.  Read the drug safety communication for more information on these studies.

BACKGROUND: Drospirenone is a type of female sex hormone called a progestin. Most birth control pills contain two types of hormones–estrogen and progestin.  Birth control pills work by preventing the release of eggs from the ovaries (ovulation) and changing the cervical mucus and the lining of the uterus to prevent pregnancy. Brand names of drospirenone-containing products include Yaz (generics Gianvi and Loryna), Yasmin (generics Ocella, Syeda, and Zarah), Beyaz, and Safyral.

RECOMMENDATION: If your birth control pill contains drospirenone, do not stop taking it without first talking to your healthcare professional. Contact your healthcare professional immediately if you develop any symptoms of blood clots, including persistent leg pain, severe chest pain, or sudden shortness of breath. If you smoke and are over 35 years of age, you should not take combination oral contraceptives because they increase the risk that you could experience serious cardiovascular events, including blood clots.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

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