Docket Management
Docket: 95N-0304 - Dietary Supplements Containing Ephedrine Alkaloids
Comment Number: EC -1378

Accepted - Volume 326

Comment Record
Commentor Mr. Brian Fennen Date/Time 2003-04-05 02:04:07
Organization Council of Acupuncture and Oriental Medicine
Category Association

Comments for FDA General
Questions
1. General Comments Docket No. 095N--0304 BEFORE THE UNITED STATES OF AMERICA DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION COMMENTS OF THE COUNCIL OF ACUPUNCTURE AND ORIENTAL MEDICINE ASSOCIATIONS AND THE CHINESE HERBAL MEDICINE COALITION ON THE PROPOSED RULE FOR DIETARY SUPPLEMENTS CONTAINING EPHEDRA ALKALOIDS UPON THE REOPENING OF THE COMMENT PERIOD April 4, 2003 The Council of Acupuncture and Oriental Medicine Associations is the largest representative organization for professionally licensed practitioners of traditional oriental medicine who are specifically trained, examined, and licensed to prescribe and dispense dietary supplements, herbs, plant, animal, and mineral products that are not dangerous drugs or controlled substances. We have previously commented on legislation that would regulate the packaging and labeling of products containing ephedrine alkaloids, and also submitted comments to the FDA on the original 1997 proposal. In response to our testimony and the testimony of others, legislation in California and other states has been amended to take into consideration the continued availability of ephedra-containing products to trained and licensed health care professionals. In 2002, after three years of successive attempts, and after adopting revisions and amendments recommended by the dietary supplement industry and by licensed health care professionals, California passed a new law that sets labeling standards for dietary supplements containing ephedrine alkaloids. (SEE ATTACHMENT 2). Please take into serious consideration the fact that Ephedra is the very first herb that is taught in traditional Chinese herbal medicine, and that it is typically used in a manner consistent with OTC cold remedies; namely for bronchial and sinus congestion related to upper respiratory conditions, and only for short durations. It is never prescribed for weight loss. It would be a direct insult to many traditional Asian cultures if you were to single out ephedra. Recently, the death of a Major League Baseball pitcher was attributed to ephedra without any substantiating evidence. By immediately pointing the finger at the “dangers of ephedra,” attention was steered away from more thorough investigation into abuse by professional athletes, team owners, managers, and physicians who all have financial incentives to contribute to the behaviors that lead to such tragic and unnecessary deaths. The true villains are policy-makers who have allowed the American public to go uneducated about the relationship between diet, exercise, and health, and which allow the diet and weight lose industries to take advantage of their ignorance. Back to the issue at hand..... The following are our comments: 1. LABELING STANDARD We understand that the FDA is proposing specific labeling standards for dietary supplement products that contain ephedrine alkaloids. (ATTACHMENT 1) RECOMMENDATION: Adopt the labeling standards California Health and Safety Code, Section 110423. This law was the result of years of negotiations between legislators, the dietary supplement industry, and licensed health care professionals. The law went into effect January 1, 2003, so most manufacturers should already be in compliance, as California is home to many of the manufacturers and consumers of these products. (SEE ATTACHMENT 2). Furthermore, we recommend that you allow the same exemption that the California law allows for products sold directly to “a licensed health care practitioner practicing within his or her scope of practice who prescribes, dispenses, or both, herbs in the course of treatment of patients under the care of the licensed practitioner.” The FDA’s proposed labeling standard shows certain bias that are not substantiated by the available data. For example, you fail to list coffee and tea in your list of substances with which the “risks of serious side-effects from this product can increase.” In fact, the weight-loss products associated with adverse events usually contain much higher concentrations of caffeine than they do ephedrine. You also recommend that consumers “contact a doctor” for various concerns. Some doctors have their degrees in engineering and other non-health related subjects. Using the phrase “consult a physician or licensed qualified health care professional” would be more appropriate. Our previous comments from 1997 still stand. (SEE ATTACHMENT 3) 2. SIGNIFICANT RISK UNDER ORDINARY CONDITIONS OF USE We understand that FDA also intends to consider, whether in the FDA should determine that dietary supplements containing ephedrine alkaloids present a “significant or unreasonable risk of illness or injury under conditions of use recommended or suggested in labeling, or if no conditions of use are suggested or recommended in the labeling, under ordinary conditions of use.” RECOMMENDATION: We do not believe that sufficient evidence exists to determine that dietary supplements containing ephedrine alkaloids present a significant or unreasonable risk of illness or injury under ordinary conditions of use. Since we consider “ordinary conditions of use” for ephedra and products containing ephedrine alkaloids to be for upper respiratory conditions for short durations (less than 2-3 weeks), and since such use poses minimal risk, we find that no such determination is necessary. However, and more appropriately, the FDA should probably consider that the very nature of using dietary or pharmaceutical products for weight loss is simply unnatural, and does pose a significant and unreasonable risk of illness or injury. Once again, it is the use of the product, and not the contents, per se, that present the danger to the consumer. 3. ADDITIONAL LEGISLATIVE AUTHORITIES We understand that the FDA is seeking comment on what additional legislative authorities, if any, would be necessary or appropriate to enable FDA to address this issue most effectively. RECOMMENDATION: We do not recommend any additional legislative authority in regards to dietary supplements at this time, though we may not be opposed to efforts that strike some balance of safety and consumerism. SUGGESTION: We feel that the FDA should consider whether to use its existing legal authority and persuasive powers with existing medical experts to simply classify obesity and related conditions of excess weight, including the psychological obsession or desire to be thin without exercise, as true medical conditions, and to classify any product or device used to correct such medical conditions, including weight loss products, as being used for medical purposes, and to regulate such products and devices accordingly. As such, “dietary supplements” used for weight loss would no longer be classified as dietary supplements, but as “drugs.” Respectfully Submitted, Brian C. Fennen Executive Director Council of Acupuncture and Oriental Medicine Associations 1217 Washington Street Calistoga, CA 94515 ============================== ATTACHMENT 1 - FDA’S CURRENT PROPOSED LABELING FOR EPHEDRINE ALKALOID PRODUCTS [PRIMARY LABEL] WARNING: Contains ephedrine alkaloids. Heart attack, stroke, seizure, and death have been reported after consumption of ephedrine alkaloids. Not for pregnant or breast-feeding women or persons under 18. Risk of injury can increase with does or if used during strenuous exercise or with other products containing stimulants (including caffeine). Do not use with certain medications or if you have certain health conditions. Stop use and contact a doctor if side effects occur. See more information [...] .” [END PRIMARY LABEL] [SECOND LABEL TO READ]: This product contains ephedrine alkaloids, which can have potentially dangerous effects on the heart and central nervous system. ** Do not use with - a monoamine oxidase inhibitor (MAOI) or 2 weeks after stopping a MAOI drug; - certain drugs for depression, psychiatric, or emotional conditions; - drugs for Parkinson’s disease; - drugs for obesity or weight control; - methyldopa ** Contact a doctor before using this product if you have or ever had - heart disease, high blood pressure, thyroid disease, seizure, diabetes, depression, other mental, emotional or behavioral conditions, glaucoma, or difficulty urinating due to prostate enlargement. ** Stop use and contact a doctor immediately if these side-effects occur - dizziness, sever headache, rapid and/or irregular heartbeat, chest pain, shortness of breath, nausea, loss of consciousness, or changes in emotions or behavior (such as depression, hallucinations or severe mood swings). ** Your risks of serious side-effects from this product can increase - with increase dose, frequency, or duration of use; - if you take it with other dietary supplements containing ephedrine alkaloids (such as ephedra, ma huang, sida cordfolia); - if you take it with additional products containing stimulants, such as caffeinated beverages and foods (including dietary supplements containing guarana, kola nut, mate, yohimbine/yohimbe, citrus aurantium); - if you take it with medications containing synephrine, phenylephrine, ephedrine, pseudoephedrine, or phenylporpanolamine; - if you use it before or during strenuous exercise. END SECOND LABEL ==================================== ATTACHMENT 2 - CALIFORNIA HEALTH AND SAFETY CODE, SECTION 110423 California Senate Bill 1884 amended the California Health and Safety Code, Section 110423 to read: Article 4. Dietary Supplements 110423. (a) (1) The sale or distribution of any dietary supplement product containing ephedrine group alkaloids is prohibited unless the product label clearly and conspicuously contains the following statement: THIS PRODUCT HAS (INSERT THE AMOUNT OF PRODUCT) MILLIGRAMS OF CONCENTRATED EPHEDRINE GROUP ALKALOIDS PER SERVING IN THE FORM OF HERBAL EXTRACTS. (2) The sale or distribution of any dietary supplement product containing ephedrine group alkaloids is prohibited unless the product label clearly and conspicuously contains the following warning: (A) WARNING: NOT FOR USE BY INDIVIDUALS UNDER THE AGE OF 18 YEARS. DO NOT USE IF PREGNANT OR NURSING. Consult a physician or licensed qualified health care professional before using this product if you have, or have a family history of, heart disease, thyroid disease, diabetes, high blood pressure, depression or other psychiatric condition, glaucoma, difficulty in urinating, prostate enlargement, or seizure disorder, or if you are using a monoamine oxidase inhibitor (MAOI) or any other dietary supplement, prescription drug, or over-the-counter drug containing ephedrine, pseudoephedrine, or phenylpropanolamine (ingredients found in certain allergy, asthma, cough or cold, and weight control products). (B) Do not exceed recommended serving. Exceeding recommended serving may cause serious adverse health effects, including heart attack and stroke. (C) Discontinue use and call a physician or licensed qualified health care professional immediately if you experience rapid heartbeat, dizziness, severe headache, shortness of breath, or other similar symptoms. (D) Individuals who are sensitive to the effects of caffeine should consult a licensed health care professional before consuming this product. (E) KEEP OUT OF REACH OF CHILDREN. (b) The sale or distribution of dietary supplements containing steroid hormone precursors is prohibited unless the product label for these dietary supplements clearly and conspicuously contains the following warning: WARNING: NOT FOR USE BY INDIVIDUALS UNDER THE AGE OF 18 YEARS. DO NOT USE IF PREGNANT OR NURSING. Consult a physician or licensed qualified health care professional before using this product if you have, or have a family history of, prostate cancer, prostate enlargement, heart disease, low good cholesterol (HDL), or if you are using any other dietary supplement, prescription drug, or over-the-counter drug. Do not exceed recommended serving. Exceeding recommended serving may cause serious adverse health effects. Possible side effects include acne, hair loss, hair growth on the face (in women), aggressiveness, irritability, and increased levels of estrogen. Discontinue use and call a physician or licensed qualified health care professional immediately if you experience rapid heartbeat, dizziness, blurred vision, or other similar symptoms. KEEP OUT OF REACH OF CHILDREN. (c) The product label for any dietary supplement product containing ephedrine group alkaloids or steroid hormone precursors shall clearly and conspicuously display the following statement: To report any adverse events call 1-800-332-1088. 110423.2. (a) It is a misdemeanor for any manufacturer, wholesaler, retailer, or other person, to sell, transfer, or otherwise furnish a dietary supplement containing ephedrine group alkaloids or steroid hormone precursors to a person under 18 years of age. (b) A seller shall request valid identification from any individual who attempts to purchase a dietary supplement containing ephedrine group alkaloids or steroid hormone precursors if that individual reasonably appears to the seller to be under 18 years of age. (c) Notwithstanding subdivisions (a) and (b), a retail clerk who fails to request identification pursuant to subdivision (b) shall not be guilty of a misdemeanor pursuant to subdivision (a), subject to any civil penalties, or subject to any disciplinary action or discharge by his or her employer. This subdivision shall not apply to a retail clerk who is a willful participant in an ongoing criminal conspiracy to violate this article. 110423.4. (a) This article shall not apply to a licensed health care practitioner practicing within his or her scope of practice who prescribes, dispenses, or both, herbs in the course of treatment of patients under the care of the licensed practitioner. (b) This article shall not apply to herbal products that are sold or distributed directly to a licensed health care practitioner when the herbal product is used solely for the purpose of the treatment of patients under the care of the practitioner. 110423.6. (a) Except as provided in subdivision (b), a retail establishment that sells, transfers, or otherwise furnishes a dietary supplement product in violation of Section 110423.2 shall not be guilty of a misdemeanor pursuant to subdivision (a) of Section 110423.2 if all of the following conditions are met: (1) Every checkout clerk at the retail establishment has completed standardized training that includes, but is not limited to, the law with respect to selling dietary supplement products subject to this article, methods of easily identifying dietary supplement products subject to this article when checking out customers, and procedures for requesting identification from any customer attempting to purchase dietary supplement products subject to this article who reasonably appears to the clerk to be a minor. (2) Every checkout clerk at the retail establishment is provided with training updates that cover any changes in the law with respect to selling dietary supplement products subject to this article and any other responsibilities of the retail establishment under this article. (3) Every programmable checkout scanner or computer used to check out customers with purchases is programmed to identify dietary supplement products subject to this article at the checkout station. A retail establishment that does not use programmable checkout scanners or computers is not required to satisfy this condition. (4) Every checkout clerk has received a written list of dietary supplement products subject to this article that are sold by the retail establishment that may be posted at the checkout station for easy access. (b) Notwithstanding the fact that a retail establishment has met all of the conditions specified in subdivision (a), the retail establishment shall be guilty of a misdemeanor pursuant to subdivision (a) of Section 110423.2 if the retail establishment violates this article three or more times in a 12-month period. 110423.8. Nothing in this article limits or restricts any rights, remedies, or duties otherwise applicable by law. SEC. 2. No reimbursement is required by this act pursuant to Section 6 of Article XIII B of the California Constitution because the only costs that may be incurred by a local agency or school district will be incurred because this act creates a new crime or infraction, eliminates a crime or infraction, or changes the penalty for a crime or infraction, within the meaning of Section 17556 of the Government Code, or changes the definition of a crime within the meaning of Section 6 of Article XIII B of the California Constitution. SEC. 3. The provisions of this act are severable. If any provision of this act or its application is held invalid, that invalidity shall not affect other provisions or applications that can be given effect without the invalid provision or application. ================================================ ATTACHMENT 3 - CAOMA COMMENTS SUBMITTED TO FDA IN 1997 August 16, 1997 Re: Proposed Ephedrine Regulations Dockets Management Branch HFA-305 Food and Drug Administration 12410 Parklawn Drive, Room 1-23 Rockville, MD 20857 To Whom It May Concern, As Licensed healthcare professionals, we applaud your efforts to protect the public from mislabeled products. Yet, due to the potential negative impact on our privilege to prescribe herbs to our patients, we are requesting further clarification and amendment to your proposed regulations of ephedrine-containing products The first thing we would like to observe is the confusion of both the public and professionals on the difference between the effects of “ephedrine” and “ephedra.” Many of the reports state first that an illness or death was related to ephedrine-containing products, then state that the most common source of ephedrine is the herb ephedra. While no claim or evidence is presented that the illnesses were actually attributed to ephedra in the products, or even that the products contained ephedra, the names ephedra and ephedrine are so similar, and the reports so vague on the distinction, that many assume that it was ephedra in the products that caused the problems. Further confusion results when the reports refer to a “list of ingredients” that includes ephedra, not stating what was actually assayed from a sample of the product. Has it been clearly established that the herb ephedra was the cause of any of the illnesses, or were they all due to concentrated or extracted ephedrine and ephedrine-related alkaloids? It is also noted that most of the problems occur when ephedrine is mixed with caffeine and other stimulants. If this is the case, then concurrent requirements to label coffee with warnings about palpitations, nervousness, anxiety, spontaneous perspiration, etc.; and alcoholic beverages with warning of gastrointestinal bleeding, cirrhosis of the liver, heart failure, respiratory arrest, and death should be forthcoming. Is the FDA going to be propose regulating other products containing potentially abused chemicals, such as caffeine and ethanol? Two years ago, the FDA proposed to remove oral ephedrine products from the OTC market, based on their use in the production of illicit drugs (methamphetamines) and on their misuse and abuse as stimulants and for weight loss. Indeed, it was determined that the OTC drugs had become an economical source of raw material for illicit drug production. OTC bronchodilators contain dosages of 12.5- 25 mg, much higher than those you are proposing for ephedrine-containing dietary supplements (8 mg). Is the FDA proposing to restrict access to high-dosage OTC ephedrine products at the same time it regulates dietary supplements containing ephedrine? Regarding dosages, we would like to note that your dosages for the use of ephedra in Chinese herbal formulations may be incorrect. While specific herbal “prescriptions” typically contain 3-9 grams of ephedra, the prescriptions are for 2-6 dosages taken over a one- or two-day period. In Docket No. 95N-0304, RIN 0901-AA59, it is stated: “In the traditional medicinal use of Ephedra, the raw botanical was administered, either alone or more commonly combined with other specific botanicals, in the form of a water infusion (tea), three times a day. Traditional treatment was prescribed by a trained health practitioner based on the evaluation of a particular patient and was predominately for short term use. Commonly used dosages of the raw botanical ranged from 1.5 to 9 grams (g), generally averaging 5 to 6 g of Ephedra per dose (Refs. 14 and 146). Tyler has estimated that a tea made from 2 g of the raw botanical Ephedra (containing 1.25 percent ephedrine) will yield a dose of 15 to 30 mg ephedrine (cited in Ref. 147). Thus, use of 5 to 6 g of the raw botanical Ephedra, an average amount used in a tea could yield a dose of ephedrine ranging from approximately 38 mg to 75 mg.” Tyler incorrectly assumed that the 1.5 to 9 grams per prescription was for a single dose, then estimated, but did not measure, the quantity of ephedrine in the resulting tea. However, if accurate, it would actually represent single dosages of 5 - 45 mg, and daily dosages of 12 - 135 mg, which is quite a large variation, and makes it reasonable to request an accurate measurement before establishing scientifically-based dosage regulations. The report correctly points out that individual patient characteristics are taken into account, and that warnings and contraindications are given. In other words, it is not a random “take-as-much-as-you-like-in-spite-of-your-pre-existing illness situation.” A small woman gets a small dosage. A hypertensive patient gets none. This mirrors a common error in acupuncture research in this country when poorly trained individuals are used to give the study treatments. Have the researchers actually measured the quantity of ephedrine found in common Chinese herbal formulations which were prescribed and given by licensed practitioners? You must understand that practitioners of Traditional Chinese Medicine (TCM) are trained, tested, and licensed to practice herbology in many states. In California, we have been licensed to prescribe herbs for many years with few reports of problems. What problems do arise are usually attributable to imported, pre-packaged, and mis-labeled herbs from China, Taiwan, and Hong Kong which were adulterated with western-type pharmaceuticals. We value our privilege to treat our patients both externally with acupuncture, and internally with herbs, and would not knowingly endanger anyone. Also, we especially note that Ma Huang (ephedra) is the first herb to be taught in the traditional Chinese system of herbology. Herbs are classified into more than two dozen categories, and always start with ma huang as the first herb of the first category. To take away access to this herb would be to show disrespect to the well-educated practitioners of an historical, traditional, and validated system of medicine, and would be similar to restricting the use of the scalpel by surgeons. Can the FDA make an exemption and distinction to allow individuals who are trained and licensed in traditional Chinese herbology, such as the Licensed Acupuncturists in California, to continue to have access to the bulk purchase of ephedra for the purpose of prescribing it to our patients? We are concerned for our profession. Many individuals of the public abuse herbs much the way they do drugs, alcohol, and food. We too are concerned for the public. We appreciate your request for comments, and hope that you will attempt to answer our questions and understand our concerns. If you have any further questions, please contact us. Sincerely, Brian Fennen, L.Ac, QME President, Council of Acupuncture and Oriental Medicine Associations President, California Association of Acupuncture and Oriental Medicine ===================================================




EC -1378