Must people die before DSHEA is repealed?

The Dietary Supplement Health and Education Act of 1994 (DSHEA) allows herbal and non-herbal supplements to be sold in the US without demonstration of effectiveness or safety. Despite recent improvements in Good Manufacturing Practices required of supplement manufacturers, these products still pose significant risks to the population simply because the hands of regulatory authorities are tied – products cannot be removed from the market until there is evidence for lack of safety, meaning that consumers must first be harmed before FDA is authorized to intervene.
After cautions a couple weeks ago from FDA, we learned today why a popular liquid dietary supplement has been causing adverse reactions – selenium poisoning:

The FDA notified healthcare professionals and patients that it has found hazardous levels of selenium in samples of certain flavors of the dietary supplement products “Total Body Formula” and “Total Body Mega Formula.” Analyses of samples by FDA have found most of the samples contain extremely high levels of selenium — up to 200 times the amount of selenium indicated on the labels of the products. The FDA has received 43 reports of persons from nine states who experienced serious adverse reactions using these products. The adverse reactions generally occurred after five to 10 days of daily ingestion of the product, and included significant hair loss, muscle cramps, diarrhea, joint pain, deformed fingernails, and fatigue. Consumers should stop taking the products and consult their healthcare professional if they experience any adverse events associated with the use of the products.

Yes, 200 times the labeled amounts of selenium:

Analyses of samples of the products by FDA laboratories have now found most of the samples contain extremely high levels of selenium–up to 40,800 micrograms per recommended serving, or more than 200 times the amount of selenium per serving (i.e., 200 micrograms) indicated on the labels of the products.

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Blue Steel Hero

No, it’s not a song by Foreigner – these are the names of two products “promoted and sold over the Internet for the treatment of erectile dysfunction (ED) and for sexual enhancement.”
In yet another instance of a trend that would be comical if not so serious, the US FDA has announced that “Blue Steel” and “Hero” supplements contain chemical relatives of sildenafil, the active constituent of the prescription medication Viagra.

“Because these products are labeled as ‘all natural dietary supplements,’ consumers may assume that they are harmless and pose no health risk,” said Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research. “But an unsuspecting consumer with underlying medical issues may take these products without knowing that they can cause serious side effects and interact in dangerous ways with drugs that a consumer is already taking.”
The undeclared ingredients in these products may interact with nitrates found in some prescription drugs (such as nitroglycerin), and can lower blood pressure to dangerous levels. Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates. ED is a common problem in men with these medical conditions. Because they may have been advised against taking ED drugs, these men may seek products like Blue Steel and Hero because the products are marketed as “all natural” or as not containing the active ingredients in approved ED drugs.

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Looking for expert commentary on generic “follow-on” biologics

Last week we spent some time discussing the shortcomings of the generic vs. brand name drug debate, focusing on an example of non-bioequivalence between the antidepressant Wellbutrin XL and its generic competitors.
Three days later, I then received an e-mail from one John Procter about a movement to get Washington to move forward on the approval of lower-priced generic biotechnology drugs now that original branded products are facing patent expiration. One source indicates that a $20 billion market value of biological products will be coming off patent by 2015. The US FDA has been reluctant to approve general formulations of biological agents that include protein hormones like erythropoietin and other protein-based therapeutics such as antibodies or antibody-toxin/radionuclide conjugates.

Dear Friend:
A virtual monopoly has limited access to biotechnology drugs for too long, costing our families billions at a time when healthcare costs continue to rise. Recent studies show Americans could save $378 billion over 20 years if generic biologics-costly drugs made by manipulating proteins-were available in the United States as they are in Europe. Although biologics are more than 20 times more expensive than traditional drugs, Washington has yet to approve generic versions in the U.S.
It is time for Washington to give us a choice of generic biotech drugs to treat diseases such as diabetes, cancer, and Alzheimer’s.
We need your help!
Watch our YouTube video [or see below the fold] to Congress, and post your own video or message to lawmakers on why access to safe, affordable biotechnology drugs should happen now!

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Don’t drink the denture cleanser, don’t swallow the inhalation capsules

The safety and effectiveness of medicines and other health products is dependent upon their proper use, particularly the proper route of administration. There are reasons why products are labeled as “for topical use only” or “do not swallow” – two recent warnings from the US FDA illustrate these issues.
Allergic Reactions with Use/Misuse of Denture Cleansers
The FDA recently announced reports of one death and 72 other adverse reactions in individuals who ingested denture cleansers meant to be used in a container with one’s dentures removed. A crucial oxidizing agent, salts of persulfate, can cause allergic reactions in susceptible individuals when swallowed, when swished in the mouth or, more alarmingly, even when residual cleanser solution remains on the dentures when reinserted.
[All sorts of biologists will recognize persulfate (ammonium salt) as the oxidizing agent used to catalyze the crosslinking of acrylamide monomers to make gels for the resolution of proteins and nucleic acids – that is, if you don’t have the luxury of purchasing per-poured gels]

An allergic reaction to persulfates may not occur after the first use or even until after many years of use. Symptoms of an allergic reaction may not appear for several minutes or even hours after actual use. Symptoms may include irritation, tissue damage, rash, hives, gum tenderness, breathing problems, and low blood pressure.

As a result of these cases, FDA is recommending that denture cleanser manufacturers clarify product instructions and offer a consumer education campaign (FDA’s PDF here). Moreover, FDA is recommending that manufacturers begin to investigate the potential for replacing persulfate with other oxidizing/bleaching agents that do not cause these hypersensitivity reactions:

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Are generic drugs inferior to the corresponding brand names?

This issue was brought up by my fellow blogger, Joseph at Corpus Callosum, following an article in yesterday’s LA Times.
For those not familiar with the concept or countries other than the US where laws may differ, generic drugs are those with the same active chemical as the originally-approved “brand name” drug. The original drug manufacturer is the one that conducts all of the preclinical and clinical safety and efficacy testing, natural product isolation and/or chemical synthesis, formulation with inactive ingredients to assure dissolution and reproducible release of the drug, etc. In return for all this work and an investment of about $800 million, the company produces a “brand name” drug for which they have a period of marketing exclusivity of roughly 17 years from the date the drug was first patented (in some cases this can now be extended another 5 years). While that sounds like a monopolistic proposition, many drugs take up to 12 years from patenting to be approved by the US FDA, meaning that the company has to recoup its investment in a rather compressed time period.
When a drug patent is about to expire, companies specializing in the manufacture of drug products compete to gain FDA approval to market a generic version of the drug without all of the huge investment made by the brand name developer of the drug. Hence, generic versions of brand name drugs are priced much lower. However, the generic company[ies] must demonstrate the so-called bioequivalence of their drug, meaning that the active component must be absorbed into the bloodstream within 80% to 125% that of the brand name drug, without any regard for the time course of that process. These studies rarely require more than a few dozen patients given a single dose of a drug. In many cases, this is adequate.

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Vibrant Denver businesswoman and philanthropist possible victim of colchicine quackery

Just a hypothesis here.
A vibrant, 55-year-old Denver-area furniture executive, Lesile Fishbein, is possibly near death according to The Denver Post:

The bubbly Fishbein, one of the most recognizable faces in the metro area because of her television ads for her company, Kacey Fine Furniture, was admitted to Presbyterian/St. Luke’s Hospital for emergency treatment on Tuesday. She had been given an injection for chronic back pain and suffered a serious reaction, the friends said. She was later placed on life-support, which was removed Friday evening. [emphasis mine]

The natural product and gout-relieving drug, colchicine, has been the cause of several deaths last year due to its inappropriate use in treating back pain and calculation errors by compounding pharmacies that provide the drug to alternative medicine practitioners. The FDA has recently announced action against those providing unapproved colchicine injectable formulations due to combined reports of at least 50 adverse reactions and 23 deaths.
I have no claim to any inside information but this very sad case smells funny to me. Potentially fatal reactions to a steroid injection for chronic back pain are incredibly rare, if non-existent. The Denver area has a high concentration of alternative medicine practitioners and I suspect that Mrs Fishbein did not receive a steroid but rather colchicine. An excellent drug when given orally, particularly for pain associated with gout, colchicine has a very low therapeutic index for safety when given as an injectable medication, hence the FDA action cited above.
I truly hope that I am wrong. Regardless, Mrs Fishbein has been part of the social fabric of Denver for many years and I enjoyed watching her commercials during my time in the Queen City of the Plains. Beyond this, she has contributed tremendously to causes throughout the Front Range area of Colorado.
Denver may lose a valued member of the business and philanthropic community. If her life has been threatened by the unapproved and reckless use of a natural product, I would hope that the practitioner responsible is prosecuted to the full extent of the law.
Our warmest wishes go out to Mr Sam Fishbein and the entire family.

Drug Risk: Benadryl® (diphenhydramine) overdoses in Oregon, Robotripping, and Purple Drank

DrugMonkey just had an interesting post about the potential influence of cocaine use trends following the 1986 death of Maryland college basketball player, Len Bias, just days after his being selected in the NBA draft by the Boston Celtics. DM’s post and the ensuing discussion got me thinking tonight about a variety of issues in substance abuse, realistic assessment of risk and, ultimately, parenting.
In the comments, I mentioned that Heath Ledger’s recent death might be a trigger for pop culture to pay more attention to the risks of recreational use of prescription and over-the-counter drugs as the attitudes toward illegal substances have grown less favorable.
Related to the DrugMonkey post, PharmGirl just tipped me off to this Benadryl nightmare at the Sweet Hill (OR) High School. Students have turned up in local emergency rooms after having taken 20 to 30 of the tablets, each containing 25 mg of diphenhydramine HCl.
At high doses, diphenhydramine’s central antimuscarinic effects become apparent as hallucinations but this is a terribly risky approach. Suppression of parasympathetic drive to the heart can cause tachycardia and lead to fatal cardiac arrhythmias. The story is deeply concerning:

Anastasia Park, 15, said she decided to try Benadryl after hearing about it from a friend. I took 30 the first time and 20 the second time,” Park said. “I got sent to the (emergency room) both times.”

Yes folks, she ended up in the ER once and still tried it again, this time taking “only” 20 tablets.
To their credit, the school district is educating students on the risks of ODing on Benadryl/diphenhydramine and sent letters home to parents advising them of this dangerous trend.

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Avery Comarow attacked by America’s Natural Physician™

[Note: I originally posted this last Thursday under another title but it got lost in other events of that day. As I find it ironic that Mr Comarow has been attacked by an alternative medicine practitioner and advocate, I find this story worthy of reposting.]
A few weeks ago the skeptical blogosphere was up in arms about an article in US News & World Report by Avery Comarow on alternative medicine services in US academic medical centers. Mr Comarow is a senior medical writer for USN&WR and best known as editor for the last 18 years of the magazine’s annual feature, America’s Best Hospitals.
To my med blogger colleagues, Mr Comarow’s article came off as unjustifiably sympathetic toward alternative medicine being practiced in major academic medical centers. Mr Comarow has two blog posts of his own on this story, here and here, the latter of which responded to the unanticipated deluge of critical comments on his story.
Truth be told, I was interviewed on background by Mr Comarow and felt that some of my most critical comments did not make it into the piece, due most likely to the complications with citing me as a pseudonymous source. While I am not a physician, I have been involved with integrative or alternative medical centers at four different US academic medical centers. However, my feeling (and my feeling alone) was that his primary intention was to get inside the mind of the patients, understand why they were pursuing alternative therapies, and grasp why major evidence-based medical centers were establishing centers of alternative/integrative medicine whose standards of proof were below that of each respective health system.
Interestingly, the accompanying video commentary on the article (here), was cited by a commenter on Science Based Medicine as follows: “The US News & World Report article has a video segment by the senior health editor. He seems to be more skeptical than the article’s author.”
The irony: the video segment was done by the same Avery Comarow who wrote the article.
So, you’d think that at least the alternative medicine community would be singing the praises of Mr Comarow’s article. You would be wrong. From Bottom Line Secrets:

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American Association of Pediatrics seeks to combat antivaccinationist misinformation

For more details on this story, you can go to Mark Chu-Carroll, Orac, Mike the Mad Biologist, or the Autism Blog. I just wanted to share my personal views on the need for childhood vaccinations and support a public information campaign from the AAP.
Until I started medical blogging, I had not realized quite how vocal was the community of individuals refusing to vaccinate their children, mostly at the urging of those who claimed that vaccines and related components caused illness in their own children. I will first say that no drug product, natural or otherwise, is completely and absolutely free of side effects. One can never predict with absolute certainty how individuals in a genetically-diverse population of 300 million Americans or some 6 billion people worldwide will respond to any product.
But as a society, we have decided that the good of the public’s health is more than offset by the risks to the few; vaccines save lives but the generation that experienced life, and death, before vaccines is increasingly dying off. My child is completely up-to-date on vaccines because I could not bear to lose her to a preventable childhood disease; we still have family and friends who survived polio with varying degrees of debilitation – and they are the lucky ones, from an era before vaccines.

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Pharmacology of Heath Ledger’s death

I’ll leave my neuropharmacology and neuroscience colleagues to comment in greater detail on this story (see earlier DrugMonkey post), but this report is just in from AP on Heath Ledger’s toxicology report:

The cause of death was “acute intoxication by the combined effects of oxycodone, hydrocodone, diazepam, temazepam, alprazolam and doxylamine,” spokeswoman Ellen Borakove said in a statement.

I haven’t seen a copy of the report itself (maybe Smoking Gun will have it soon) but plasma concentrations of each were not noted. However, this was the statement from the family:

In a statement released through Ledger’s publicist, the actor’s father, Kim, said Wednesday: “While no medications were taken in excess, we learned today the combination of doctor-prescribed drugs proved lethal for our boy. Heath’s accidental death serves as a caution to the hidden dangers of combining prescription medication, even at low dosage.”

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