| Comment Record|
Mr. Jim Waddell ||
2003-04-04 15:10:27 |
CA Dept of Health Services-Food and Drug Branch |
| Comments for FDA General |
1. General Comments
The California Department of Health Services, Food and Drug Branch (FDB), has the following comments on the U.S. Food and Drug Administration's (FDA's) proposed rule related to dietary supplements containing ephedrine alkaloids, Federal Register: March 5, 2003 (Volume 68, Number 43) pages 10417-10420. Our suggestions include changes in the warning statement, inclusion of the MedWatch number with label warnings, and the establishment of standards for determining “significant or unreasonable risk of injury”.
The proposed warnings include a 75-plus-word statement on the principal display panel (front panel) of product labels and a hanging tag affixed to the product container listing 25-plus-situations when consumers should not use the product, consult their physicians before using the product, or stop using the product and contact their physicians immediately. FDB believes that the warning proposed to appear on the principal display panel is too long and should be modified to read, Warning: heart attack, stroke, seizure, and death have been reported after consumption of ephedrine alkaloids contained in this product. FDB also suggests the following modifications to warnings proposed for the hanging tag: 1). dose should be changed to serving size to distinguish these products as dietary supplements from drugs; 2). Sida cordifolia should be followed by its common name in parentheses (Country Mallow); 3). the statement if you take this with medications containing synephrine, phenylephrine,... should specify oral medications since there is no evidence that topical ophthalmic products containing the named drugs increase the risk of adverse effects from dietary supplements containing ephedrine alkaloids.
If FDA cannot find that dietary supplements containing ephedrine alkaloids are adulterated under FD&C, Section 402 (f)(1), FDB believes that FDA's Medwatch number needs to be included with any label warnings on these products. Both California and Texas law require that labels of dietary supplements containing ephedrine alkaloids display FDA's Medwatch number and on June 14, 2002, Tommy Thompson, Secretary, U.S. Department of Health and Human Services Secretary, recommended that manufacturers include this number on their dietary supplements containing ephedrine alkaloids.
The RAND report, Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects, prepared for the Agency for Healthcare Research and Quality and the U.S. Department of Health and Human Services, reviewed 1,783 adverse reaction reports from FDA's Medwatch program and 15,951 consumer health complaints reported to Metabolife International, manufacture of Metabolife 356. Metabolife 356, a dietary supplement containing ephedrine alkaloids, includes an 800 number on its label for Health Information. Metabolife International, one of more than 150 manufacturers of dietary supplements containing ephedrine alkaloids, received roughly nine times more consumer health complaints then FDA received for all dietary supplements containing ephedrine alkaloids. Unfortunately, consumer complaints received by Metabolife International were of little use in assessing health risks from these products because of inadequate documentation of adverse reactions and unreliable estimates of the number of users. Metabolife International did not record age or gender in more than 50 percent of the reports it received.
It is FDB's experience that consumers and some physicians do not know whom to call to report adverse reactions from dietary supplements. Repeated news reports that FDA does not regulate dietary supplements leave consumers and these physicians with the mistaken idea that there is no resource within FDA that records and responds to reports of adverse reactions from dietary supplements. Since the Dietary Supplement Health and Education Act of 1994 places the burden on FDA to show that dietary supplements are unsafe once in the marketplace, it is imperative that consumers experiencing serious adverse reactions from dietary supplements and their physicians know to call FDA to report these reactions. Including FDA's Medwatch number on product labels of dietary supplements containing ephedrine alkaloids will provide consumers and their physicians with the information they need to report adverse reactions.
The number of adverse reactions reported for dietary supplements containing ephedrine alkaloids reveals the limitations in finding that dietary supplements are adulterated, and thereby unlawful to sell (i.e., present a significant or unreasonable risk of illness or injury). FDB believes that public health protection and industry fairness require that FDA establish standards for what constitutes significant or unreasonable risk of illness or injury for dietary supplements. Findings of the RAND report that the risk of serious adverse effects from ephedra and ephedrine in controlled clinical trials is less than 1 in a 1000, does not assure that dietary supplements containing ephedrine alkaloids are safe (not adulterated) when consumed by the general population. The RAND report recognizes that the apparent risks of drugs tested in controlled clinical trials, even when tested in individuals identified as being a high risk for adverse effects, can be substantially less than the actual risks of those drugs when made available to the general population. These standards may require additional legislative authority, but are needed as a framework for any future evaluations of dietary supplements containing ephedrine alkaloids and for evaluations of other dietary supplements posing potential health concerns. The ephedra-free weight loss supplements, commonly containing Citrus aurantium extracts, with pharmacological effects similar to phenylpropanolamine, should also be included in future evaluations.
FDB appreciates the opportunity to comment on this proposed rule. Please contact Jeff Farrar, DVM, MPH, Ph.D., Chief, Food Safety Section, at (916) 445-2263, or by email at firstname.lastname@example.org with any questions or comments.
James M. Waddell, Chief
Food and Drug Branch