| Comment Record|
Dr. Raymond Woosley ||
2003-04-03 13:14:33 |
University of Ariozna HEalth Sciences Center |
Health Professional |
| Comments for FDA General |
1. General Comments
Please substitute these comments for the those submitted on 3/17/2003 at 16:32:43. Thank you.
1. the dangers of ephedra
I am a clinical pharmacologist with over twenty five years experience in drug safety. I have a PhD in pharmacology and training in internal medicine and clinical pharmacology, the discipline of medicine that studies the actions of drugs in humans.
I have served as a consultant for the FDA since 1995 addressing the safety of ephedra and several other drugs. In 1995 and again in 2000, I reviewed over 200 cases of adverse events reported to the FDA. I also served on an FDA Center for Food Safety and Nutrition advisory committee on the safety of ephedrine-containing dietary supplements. This experience and my training in the study of drug toxicity led me to conclude that, without any doubt, ephedrine-containing products can cause strokes, heart attacks, hyperthermia, heat stroke, seizures, arrhythmias, sudden death and a large number of less severe but equally important adverse events. These facts have been known by members of the medical community for many years.
There is no “safe dose” of ephedra because it will be used without supervision and therefore the dosage will be increased in many people to the point that they sense a loss of appetite. These dosages will put those patients at risk for the serious cardiovascular complications listed above and other serious adverse reactions such as personality and behavioral changes.
2. the appropriateness of a warning label as a means of providing for public safety including comments on the warning label that they are proposing
Warning labels are not effective in this situation. They are already in place on many of the products and the serious adverse events continue to occur. This is because many people at risk do not know that they have a predisposition to ephedrine toxicity. They do not know that they have high blood pressure, excessive thyroid function, a thin blood vessel in their brain that would otherwise go unnoticed, a propensity to seizure or arrhythmia, etc. Furthermore, it is well established in medicine that there are perfectly healthy individuals who have a genetically determined super-sensitivity to the drugs that stimulate the heart and blood vessels. In these people, not only will warnings be ineffective, even low dosages will be potentially lethal.
Warning labels are also inappropriate because their presence implies to the public that the FDA has assessed “benefit” and “risk” if the FDA is warning of risk. The FDA has not assessed the value of these products and in this case, the small amount of weight loss is of unproven benefit and the risk is unacceptably high.
Likewise, it is a flawed practice to have a warning that recommends that a product being used for weight loss not be taken while exercising. Everyone in medicine and most of the public knows that exercise is an essential component of a weight loss program. To warn the public not to exercise could do harm also by interfering with effective weight loss.
3. whether the agency should find that ephedra products pose a “significant or unreasonable risk of illness or injury” and therefore take action to remove ephedra products from the market
The danger of ephedrine-containing products is their use without medical supervision and screening and in the way they are being promoted to the public. It should not be made available without some medical supervision. However, this means that it would be prescribed by physicians for a medically proven indication, perhaps weight loss. Unfortunately, the data on its effectiveness is slim. The Rand report concludes that ephedra/caffeine products have a modest ability to produce a short-term reduction in body weight. Whether the effect is sustained is unknown.
In either case, it should not be available without medical supervision or as a “dietary supplement.” Ephedra is not an ingredient in a normal nutritious diet and should not be supplemented. It is a drug, being used as a drug for weight loss and exercise enhancement (there are no data to support this use).
4. whether changes are needed in the law dealing with dietary supplements to help FDA deal with safety issues more effectively
I am not a lawyer but from the medical point of view, there is no need to change the law. DSHEA was intended to address dietary supplements. As I state above, ephedra is not a dietary component that should be given as a supplement. My interpretation of “dietary supplement” would mean that it would be a product to make the normal diet complete. A complete nutritious diet should not contain any of the herbal products such as ephedra that are being used for medical purposes. These products that have drug properties, that contain drugs, and which are being used as drugs, should be regulated as drugs, not dietary supplements (vitamins and minerals).
5. whether there are other studies available for review by the agency that would provide information on the dangers of ephedra-containing products
The Rand report was comprehensive in this regard. All of the studies of any value that are published in the literature are not relevant to the question being addressed. All reputable studies must have approval by a human subjects committee. Every study that has been submitted for approval has been required to have medical screening to exclude patients at risk of the known medical risks, i.e. strokes, heart attacks, etc. Therefore, these studies cannot be useful in assessing the risk of ephedra when it is being taken without medical supervision. The critical information in this case is the pharmacology of ephedrine which has been known for decades, the clinical pharmacology of adrenergic stimulants such as ephedrine, the understanding of the human body and its genetic variation and the analysis of the adverse events that have been submitted to the FDA. I and six other consultants reviewed these reports and we all concluded that there is a known risk of serious side effects with these products. The majority of the members of the FDA advisory committee in 1996 also concluded that there is no safe dose of ephedra when taken without medical supervision.
The only study that is missing would be unethical to perform. I do not believe a human subjects committee would allow a prospective study of the safety of ephedrine containing drugs without medical screening. Even a cohort study would be difficult because of the ethical requirement to effectively inform participants of the risk.
In summary, I strongly encourage the FDA to take swift action to remove ephedra from all products that are available to the public without medical supervision.