Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download RE:Docket No.98N-0148 ;International Drug
Document related concepts
Prescription costs wikipedia , lookup
Pharmacognosy wikipedia , lookup
Epinephrine autoinjector wikipedia , lookup
Compounding wikipedia , lookup
Prescription drug prices in the United States wikipedia , lookup
Pharmaceutical industry wikipedia , lookup
List of off-label promotion pharmaceutical settlements wikipedia , lookup
Transcript
RE:Docket No.98N-0148 ;International 1 DURK PEARSON Box 2160, TO: Dockets Food Management and Drug 12410 Comments & SANDY Tonopah, Branch Dr. , Rm. for Docket In re: Comments No. Actual and Trafficking Fed. March Abuse, Usefulness Sinica Reg. “y~ fi?~-~ a~;L,~ 98N-0148 the DRUG ADMINISTRATION Concerning Supplement Ephedra NV 89049 1-23 Rockville, Dietary Medical) as a Under MD Abuse) Docket ) DSHEA, in Ephedrine No. 98N-0148 ) and) Herb 63(52): ) 13258-13259 ) 18, 1998 ) 3 April, INTRODUCTION These Note: ephedra the herb family comments are remifentanyl. substances” apply and of to the .. MD 20857 FOOD AND Usefulness, ... Ephedrine. SHAW (HFA-~Q~J~~ Before Potential, Scheduling; Administration Parklawn Rockville, Drug TO COMMENTS comments These comments family as any FDA to dietary in SHAW ephedra herb, supplements, ephedra sinica. dihydroetorphine “isomers recommended alkaloids & SANDY ephedrine, found apply of ephedra PEARSON regarding tendered insofar to containing alkaloids ephedra only pertain ephedrine hereby OF DURK 1998 found and No or of psychotropic WHO rules in ephedra would sinica. C’ i ——- RE:Docket No.98N-0148 Durk Pearson maintaining books Their on labels United the cost them Shaw and (all are small if the FDA sale Pearson dietary & supplements by the of of and formulations and companies. The include and WHO and stems. economic were harm implement, to itself or DSHEA on herb. ephedra containing that dietary manufacturers substantial actually speech Amendment leaves herb believe would Shaw marketers and L censorship. herb suffer m censorship supplement ephedra Shaw First FDA and supplements dietary Furthermore, would Books, Choice: and manufacturing recommend, the (Warner non-misleading of such licensed three #1 best-seller Informed ephedra authors, Their copy against Pearson their and AD ~roach truthful, dietary ground to plus m health by businesses) on compliant herb and were restrictions that ... Ephedrine. California. is protected designed Pearson scientists million marketing containing are Freedom design supplements Scheduling; Scientific to public Shaw Drug and Constitution to small formulations the argues in labeling and Nevada book, States Pearson license fourth and discusses in Shaw Practical SUPP lements Nutrient Sandy include Q Extension, 1982) . the and residences best-selling Life ;International consumers of be endangered ephedra by any such restrictions. DSHEA (Dietary substantial an herbal directed statutory dietary before restrict or ephedra supplement FDA ingredients statutory ephedrine supplements on FDA legally permitted such Under the provisions of to recommend containing FDA has met & Shaw burden of containing are dietary do not proof and unreasonably that unsafe to of take believe under ephedra risky DSHEA DSHEA to action to ephedra or their that FDA or its has no herb, constituent of proof. has ephedra containing consumers that as restrict the herb any a used FDA burden that when DSHEA, supplemental their places supplement a WHO Act) to demonstrate is unreasonably sales unless Pearson is of proof and Education the authority herb burden Health prohibit ingredients. statutory Supplement when met their herb and dietary used as .. RE:Docket No.98N-0148 ;International Drug Scheduling; ... Ephedrine. directed. On the Committee Expert Supplements public the are see Pearson these & Shaw’s Containing on potential, actual usefulness as and ephedra Note FDA’s regulated the Alkaloid millions of of ephedra common Dietary 107 page & Shaw with with Dietary Please We actual filed Supplements address dangers, extant form. (attached) . they dietary the abuse dangers, supplements using only and users, itself FDA Dietary identified herb Pearson own of and ephedrine products. were American in and Containing They supplements aforementioned Americans supplements. herb food FDA’s attached by potential abuse, in the No.95N-0304: Alkaloids, the Containin9 of Comments Docket containing that Ephedrine either 107 pages DSHEA herb than by filed ephedra safer Ephedrine Alkaloid previously extant presented at length review generally comments millions we that evidence Ephedrine document shows labeling on (which comment FDA) the contrary, Expert Committee Supplements ephedrine found no found containing a few abusers among evidence or of ephedra herb trafficking in on that dietary these of many abuse containing of dietary supplements. Re illicit There dietary is no illicit supplements has already to chemical are trafficking: been designated diversion enforced potential containing by the for use ephedra Drug as Enforcement a precursor chemical under 21 herb CFR and part illicit in itself is subject 1310 Administration, in or Ephedrine herb. as a listed regulations ephedra due which to its methamphetamine manufacturing. Any recommendation ephedra herb subject to by (or ephedra the same FDA herb to WHO (or any containing restrictions as other dietary ephedrine party) supplements) itself would that be be .. RE:Docket No.98N-0148 ;International capricious, arbitrary, Administrative contrary Procedure There is no record a precursor for illicit To require make one about 1.5 kg. chemicals would be red performed a residential kitchen would require that 2,000 kg. approximately 3,000 liters and highly involved the It used as manufacture. dietary source For attached to WHO source regarding .—. . ..— . .—. volume. the used as methamphetamine would a few kilograms of other solvents. of a The few conversion liters has been) volume, performed in in extraction and with an the of solvent of huge amounts ephedra herb be an than and why for that FDA more ephedra if FDA must dietary ephedra even additional illicit ephedrine of has used never methamphetamine containing and less itself. any distinguish supplements difficulties herb reasons makes expensive difficult herb of operation prohibitively such use of extraction the from vessel of and pure ._ herb nothing of comments, regulated sinica an herb, be extracted say obvious ephedrine, ephedra be both ephedrine also first hidden, therefore, of from Obviously, disposal reasons, _ of been would to would on the one hand .- ephedra of ephedrine 107 pages (and DSHEA herb) —“ these and vessels readily illicit supplements economic herb be is and solvents magnitude It illicit the ephedrine of is obvious, a having methamphetamine of raw suspicious, in solvents. been kg. of this ever (and often of illicit cannot a violation or bathroom. approximately purchases of can be 200 scale and .. . Ephedrine. methamphetamine. approximately this herb phosphorous) operation however, of ephedra in reaction 1 kg. fact, of ephedrine, and the whole To make to Scheduling; Act. kilogram (e.g., Drug stated in the recommendations between ephedra containing ephedra on the other. .. RE:Docket No.98N-0148;International FDA , in ephedra accord herb supplements ~ itself be under no other recommendation the DSHEA with U.S. and subject circumstances be would Drug law, must ephedra to any regulated Scheduling; recommend herb be a clear same violation and of the APA. Sincerely, i. —.— —.- —___ ,_____ __ to containing additional the ... Ephedrine. Durk Pearson Sandy Shaw WHO dietary regulation, as ephedrine; of the that intent and any of .. RE:Docket No.95N-0304 ;Dietary DURK PEARSON BOX 2160, TO: Dockets Food Supplements Management & SANDY Tonopah, Branch Ephedrine Parklawn Rockville, Comments SHAW NV 89049 (HFA-305) Dr., Rm. 1-23 MD 20857 for Docket No. 95N-0304 Before FOOD AND the DRUG ADMINISTRATION Rockville, In re: Proposed rule: Supplements Ephedrine Alkaloids Fed. Reg. 62(107): June 4, 1997 Containing ) ) 30678-30724 ) ) MD Docket No. 95N-0304 ) 18 August, INTRODUCTION Durk E~ and books Their against such fourth and in the are and that is ~ California. copy SHAW and authors, three #1 best-seller Life Books, 1982) . Choice: —— non-misleading .FDA ~ speech Informed protected 1997 Their (Warner truthful, and discusses & SANDY scientists ADD roach Freedom argues PEARSON million Scientific labeling FDA censorship Shaw Nevada book, SUPD lements labels in include ~ Practical OF DURK Sandy residences best-selling on TO COMMENTS Pearson maintaining Nutrient Alkaloid and Drug Administration 12410 Dietary Containing by the cost the First to public Amendment health of censorship. Pearson and — ----- Shaw design . .—— —— .—. dietary supplement formulations and RE:Docket license No.95N-0304 them to small formulations would suffer adopted. Furthermore, herb are unreasonably the evidence under with impermissible current fact, Pearson and Proposed does & Shaw’s that the and their businesses) Proposed Rules supplements were that consumers of be endangered by actually used by the FDA labeling restraint of attempt proof, develop Rule, not a violate 107 pages herb shows FDA that & Shaw gather successful Proposed Rule arbitrary, the the First evidence new than Sincerely, Pearson Shaw herb food in are an Amendment of that meets their reconvene the , that, (attached). Sandy ephedra FDA Amendment. Durk contrary, that =pricioust First of Comments safer their supplements moreover, request if met on the extant proposals, violate has dietary are generally and is not the as directed; that Pearson that ephedra when FDA’s Rule, burden and The dietary Shaw small believe would believe labeling Constitution. Committee, and dietary in & Shaw extant prior Proposed not DSHEA unsafe form. DSHEA do presented supplements this Pearson if harm herb supplements & Shaw of proof the U.S. economic include are Alkaloids Rule. Pearson common (all EPhedrine companies. Shaw Pearson herb. ephedra dietary the Proposed burden use of the and Pearson manufacturers substantial Containin9 and manufacturing ephedra and regarding ephedra by containing marketers Supplements marketing designed supplements licensed ;DietarY withdraw unlike contrarY Please the to see RE:Docket No.95N-0304 ;Dietary Pearson Shaw’s Ephedra All quotes, Alkaloid with transcript meeting of The the FDA’s be used is a very therapeutic including foods , yogurt, health somebody Dr. Jasinski: been beans the would pharmacologic The basis is drugs false. At effect by providing eating and result from the alterations have areas been tryptophan —— VersiOn ———— in release to across the of 12 August, __ _ - AS would So of be a well profound effect and have and blood-brain 1997 4:1OPM ___ “_~_ barrier PDT; lack into 1 from coffee can get the a the foods do not psychoactive following effects the I on energy and of page of drugs a Carbohydrates, passage for 124) glucose neurotransmitters the poison you from in blood and body. is a drug tachycardia biochemical as increase is [of a food]. because being what definition, foods and 122) factor separated level, of increase between beans.11 (Vol. I pg. can a bran. definition your fat fruits is a deadly got by allows Glucose (Vol. I pg. I’ve FDA and wheat a defining disease, IOW for glucose. used juice, The in your are prevent cancer) to be marketed of of the brain “Foods foods to distinguish and basic such shown of curious a sense eating, a a food. 37): or fruits, a pharmacological cascade not cranberry and glucose now. foods most ephedrine, Many treat about from coffee have the to risk as being allowed that Committee contains foods. and Think right effect notion that various be the supplements. a drug, prunes, difficult coffee, coffee from Advisory dietary for oat bran ‘r...I was effect not of hyperglycemic.1’ drinking drinking true is hypoglycemic is very Food taken (Vol. I pg. is the is a drug. of pharmacologic have oils, IfIt’s very and what that reduce as is also who view vegetables (may Dr. Hui: someone fish on Supplements ephedra said Alkaloids purposes.’! narrow and claim vegetables, when Yetley Ephedrine FDA are is therefore purposes, garlic, 1996 that for non-therapeutic This the containing and Dr. Elizabeth to given, 27-28 believes agent, Containing Dietary numbers August FDA pharmacological a food Containing page the Comments on ephedrine-alkaloid 1. for G Supplements that levels and hormones in for example, amino acid brain, where RE:Docket it is No.95N-0304 used by the carbohydrates when pharmacological sugar here sugar tranquilizer is used and of drinks. Recently, anandamide (believed cannabinoid receptors) anandamide hydrolase found in chocolate, of temporary a “chocoholic” expression chocoholics extreme often chocolate premenopausal women days just before rate chocolate his used to as a being Screening Journal 2, 1997, of @ numbers papers in include antimicrobial, regulation, Version to help to of Westerners well of 12 August, effects, soft that ligand for an inhibitor of anandamide) are down an brain production chocoholics. intense The craving and the most over who has of the University of 23% of found in the that perimenstruum, Those of menses. than other the women also people do. time, 1997 heat and is phlegm, (Han in et of possible PDT; Foods the and preventive page “The Tea-Polyphenols,” journals, antipyretic for al, Vol. of tea are becoming as a result 4:1OPM effects eyesight, ~ Medical scientific as is eliminate Ingredients diuretic, tea improve body consumed medicine, medicinal digestion, effects commonly Chinese and Functional peer-reviewed as infant discovered many have eliminate The health growing it; psychoactive chocolate’s Rozin health Anticarcinogenic 8). in In traditional Nutraceuticals, pg. for pleasurable sleeping and calms containing is one of the most various reduce of effects. sinensis) have detoxification, Paul more a drops psychoactive breaks other the start treatment diuresis, each and after as have been implies chocolate in the world. recognized being crave (Camellia beverages well coworkers are pharmacological Tea that account craving. and to natural may with a crave traditional oleylethylamide, itself vie Pennsylvania These of few often caffeine has the (the enzyme sense This and it be which a infant for those fact, and people that known chocolate, to serotonin, as a tranquilizer, known are largely in Alkaloids tit.” foods tea, coffee, food as a medicine. are consumed including using Ephedrine of Some of a crying a “sugar components manufacture is well tongue is called Many effects It Containing agent. thus anxious, on the water the sedating effect. in water Supplements in brain and calming natural ;Dietary 2 1 No. known publication to of which effects immune function effects in RE:Docket No.95N-0304 ;Dietary cardiovascular disease was tea’s based British on craving turn resulted is both effects these foods provides active a The foods are suggest use being that the individual of whether who seek foods the public and Poryzees’ domain Yankelovich Industry: Journal 2 1997, (especially something of 12 August, (an oleic the be (for health components of sunflower oil). We all foods and Functional therapy, U.S.), FDA 1997 must 4:1OPM studies and recent the Food Issues,tl Vol. 1 No. with self- to a health include disease enhancement, Wellness how page 3 is element FDA in Childs and Foods, interests consider consumers Development or spiritual PDT; of comfortable loss. of their study, subscribe all effect. such Foods performance weight philosophy the foods and capricious inquiries, ~ Medical and effect, amounts HealthFocus are on smaller upon Product with made to benefits “Functional to by market consumer and due in wines. arbitrary based same example, or of risks on FMI the herb cannot to judge individuals for disease Hence, way Functional These the high of alcoholic of individual larger Gilbert’s (Childs, products in hops identifiable Economic credo. but experience created in tea effects different drugs foods health, annual of a personal consumers. Version 30). an as Wrick, survey, of prevention, is Nutraceutical, pg. maintenance not the is or is not a pharmacological research @ Thus, of a pharmacological ratio enhance Consumer, selection of the there that and contains users, the the effects and of which effects. and polyphenols foods reasonable there Furthermore, as (for example, only that pharmacological of different or absence that so strong content, form in beer isolated is on the basis basis the of tea the China, and Alkaloids Indeed, China. some alcohol such days when components for in between engineering) selected drugs these against Certainly their ingredients, particularly genetic to of the presence with psychoactive significantly distinction the basis for effects) was use and has pharmacological ingested stimulant/sedative of due Western effects war Ephedrine effects. deficit opium and wine. are diuretic of trade British beer alcohol beverages other balance Containing Traditional stimulating consumed beverages of and and a medicine include amount tonic in the a food Other and cancer. for tea’s it led to a severe Supplements and in fact to these censorial or RE:Docket No.95N-0304 prohibitive and, policies thus , the the intended ;Dietary Supplements is going to be perceived likelihood purpose. of such is exceedingly It define attempts to nutritive and not therapeutic was the message the Rule, fits foods within as the the ambit is doomed being likely reach that for the FDA/s are only Indeed, this FDA must a new will, consumers that of this, withdraw conclusion and Alkaloids effective to failure. Because Congress’s Ephedrine these substances Committee, of by policies those of the DSHEA. re-convene Containing that re-propose a new Rule. 2. Individuals ephedra that herb attacks heart million and just Dennis Jones: estimate but ephedra kinds millions emphasis that.” : “And I don’t public Centers age. for The Committee the How , then, could each times I just are did @ I to low that (Vol. I point of these that you 12 contain incidence II pg. Chairman give My to the incidence (Acting we can 10 make (Vol. 250) herb. for whether a and pg. this products know about estimate.li occurs. “ that of wanted a very Askew available such as Control, not provide their two risks of ephedra the FDA of 12 August, user products], year that taking need think is Disease during evaluating Americans four is (Vol. of users Wayne agencies FDA the 118, of the an answer to 119) information including Version E. in ephedra stores.11 spontaneously Dr. (Vol. II pg. But the than the is how many used number people ~ have [of and we are seeing added) Committee) day Chassy: effects, evidence caused to know expected we food have M. of of serious crreater per million Bruce that enormous 8 not using in question. health people alkaloids is= the to Dr. if doses be is while products we need would figure “.. the other P9 “ 277) that half 5 or strokes products thing strokes the period from is One II..the a that’s weeks, and Ford: attacks or ephedrine-containing or strokes. during Mr. by herb attacks population heart ephedrine-containing the ephedra heart the or having or the 1997 4:1OPM from the for number Public the this day a Health heart in PDT; which members “page 4 Service and incidence information alkaloid-containing Committee sources, attack essential meeting of they to were products. know whether RE:Docket the No.95N-0304 incidence population of the than population JUly make dangers pg. of using the scientists flaws and the untreated there may be of on rates bias to about I pg. 198: reactions FDA adverse This crude rates, reporting reports these and follow a adverse up.’l reports This against withdraw the conclusion that 3. reaction Rule, reports supplements. re-convene this exhibits have FDAJs the from Version ———— of 12 August, 1997 4:1OPM PDT; —._____ _. _ _.__—____ — adverse of we present in of many ephedra case (and MSG) that page 5 FDA has OTC this, reach drugs FDA must a new a new Rule. against claiming of dietary and of complaints in nothing the supplement bias of individual done of these analysis of Committee, infamous the FDA by noting: use to has thus hence, and, letter and re-propose the of the concerns containing Because thousands of aspartame concern of prescription error, of been FDA the view the Love times.~1) , ‘Ifollow up” supplements. treatment There users supports publicized of review alkaloid in favor corrects FDA’s and has the evidence the that heightened spontaneous careful that is limited the caution safety with to in our their not that ephedra bias dietary includes review~l neglect a long-standing is also FDA monitoring lead events there number inherent not account by Dr. Lori association show on does The conclude We think IIcareful a supplements. and but study of heightened monitoring COIIUIteIltSwill approaching had in could publicized possible antihistamines, that when and (Vol. 350, contains scientists (see statement atmosphere antihistamines. user general of the cardiac events. products reported this background a possible reporting bias. They II...the FDA has been carefully drug the Lancet agonist biases ‘~...we have a potential the Alkaloids Evaluation of analysis reporting ephedra Drug on a study First, of in ephedra-containing creating type These potential its concerns Vol. a for of to ~ adrenergic of the data. population.” awareness FDA, In commenting subject spontaneous for in a letter II...this be Ephedrine greater expected Center non-sedating may were been FDA’s 69). misinterpretation for the state: Containing age range? the same point 5, 1997, events have in the users’ at Supplements adverse would Scientists Research ;Dietary adverse dietary received aspartame by (or RE:Docket MSG) No.95N-0304 caused adverse Strokes of excess events, and seizures excitotoxic acids) activity, caused them. of but aspartame the categories number scientific of MSG) use is safe. were done largely would that be aspartame The association effect. of the FDA has exchange Dr. being of young event, of analysis Dr. been ~ believe don’t (emphasis broken added) I pg. down. we’ve Here, of 12 August, ““ .-—. information Dekker, 1984) substance as experience on Filer, and cause the and of Health, with containing adverse products. However, note the and Dr. Jasinslci: ‘tBut that’s associated, ‘lA certain or some “. .have and percentage unexplained you done some sort data?” (Vol. actually than to the FDA of same from strokes in evidence quality Department is different.11 to die excluded and Dr. Culmo 81): known Stegink a the normal with Hence, evidence. it’s associated.” on this Culmo recent between I pg. are going and not of the Texas on this 81-82 (vol. of of ephedra-alkaloid and associated people cardiac Version I pp. is Texast heavily Jasinski causal event of Marcel studies on were (For (and non-insulin- trials example, the (and MSG) individuals consumption T. Culmo, from users on Vol. the or serious. the by safety of complaints for despite of no better Biochemistry, adverse relied be increased aspartame ephedrine. thousands them that individuals may see, of state reports safety of include with the wide convinced safety as such trials @ Dr. Cynthia discussed event an to (or MSG) has (some aspartame the glutamic of aspartame of trials, Physioloqv MSG) none just fact is trials people despite As~artame (and and aspartame) it Alkaloids effects aspartame in contain safety expected some safety occurrence may (and phenylketonuria (and MSG) events, foods the known to reconsider with clinical for ephedrine, adverse The ; that refused aspartame disease, aspartame mean because on normal diabetes) for in However, dependent loss aspartic (e.g. Ephedrine and strokes. acid doesn’t that seizures with consistently of individuals the weight that Containing “consistent” complaints included cardiovascular are foods studies individuals including (and MSG) of Supplements amino FDA has use large ;Dietary But, ever Dr. 1997 82): “It’s again, qone Culmo 4:1OPM we keep ~ backs PDT; tabulated. saying record It hasn~t associated. and said caused. down under the pressure page 6 RE:Docket No.95N-0304 of comments tough that, and cause and withdraw conclusion 4. FDA all those this is a problem that they may fatal, have for having probably only a occur food , the reach those same warnings. severe Most such in childhood. protects who already allergic will should food not not use not However, components that protein, reactions find out food sensitivity -- they are with the Rule, the food discoveries labels sensitive to the error, be warning re-convene this can requiring eating that exists corrects by shows know as withdraw a new conclusion to new of them may to peanut But this situation FDA must as generally reaction. a in the warning. sensitive must a new Rule. warning many Texas FDA reach that because such can cause People clear just are sensitive. sensitivities, others a population conditions they bias, Committee, even those of Alkaloids associations and re-propose products all not know hospitalization. and error, the these Because that the medical food while argues containing they Some this are knowledge, called the Ephedrine associations her publicly in the sensitive ephedra-alkaloid know to re-convene corrects The that, Containing these relationship. Rule, that that has never effect the protect and of Health Supplements admits associations, Department a ;Dietary ephedra the a herb Committee, and re-propose a new Rule. 5. FDA any benefits use, are this benefits any have Committee used benefit committee safety The Version been the members they Committee use. totally by many members However, users, benefits placebo FDA to FDA describes of 12 August, help decreed (1996) were (and some that forbidden of in weight could not PDT; of there consumers or energy. A number controlled scientific these during cited is thermogenic 10SS. be to consider 4:1OPM which This considered. of the problem the Committee’s 1997 loss ephedrine complained consider unacceptable. double-blind showing to of benefits as weight published not In the absence such successfully when risks of assessing, meeting) that the herb described peer-reviewed studies be of ephedra makes are capable of instructed and was the can one Several of considering benefits. conclusions page 7 on determining RE:Docket a safe No.95N-0304 level that many were unaware (in safety, margin of safety heard with, there’s afternoon taken well, off what has risk/benefit at answer to when table are to all [by then don’t have FDA] they issue of a because for and it use because of use leaves this you for. of safety, ~ a and what purposes to q perceived notes that indication the margin infinity the purported going “FDA Alkaloids level.11 a loss some the we 29), “With of to have to that, go ~ somewhat have heck 222): Ephedrine stated a safe II pg. is that the the no clear frankly, left you really this being I’m pg. Committee for determining (Vol. Containing proposal, of the Food Advisory Ricaurte of Supplements rulemaking of a basis margin are the members Dr. George I’ve ;Dietary quite can’t benefit.” If @Og (emphasis added ) Dr. going Inchiosa to be very product that warnings because really, (Vol. confusing claims you have or no no claimed benefit, (emphasis serious this water event like why and Because of FDA’s could not analysis could only capricious accord with withdraw 6. than that Rule, look to be increased. to increase only a condition there’s no margin is at a list of And, so, information Dr. Ricaurte (comments it’s of more that since of safety says directed no microphone, that can than consider low dose 1997 to the thereby the error, 4:1OPM of already consider PDT; page food 8 sounds a one more okay?!’ (that risk/benefit in arbitrary that Committee, are to Committee and re-propose supplements If you no resulting Because imagine I come Committee’s recommendations re-convene form. the evidence. this when analysis, charge risk, I can “Because a scientific considered) to Dr. Yetley) risk, and electrocuted.” dietary of 12 August, who this tremendous with someone this corrects in common a I agree incorrect be consumer, has trying 149) scientific Ephedra foods Version the the conclusion very yet imagine added) I get benefits and on I go to church the information Dr. Croom (Vol I pg. II.. .as a scientist, when of “... I could are going we’re IISO, therefore, be calculated.” spill for the warnings disinformation 227): nothing, in an age where confusion.” II pg. are this, not FDA reach a in must new a new Rule. less dangerous poisoning as a RE:Docket result No.95N-0304 of bacterial year. This does disabilities strokes I@ resulting heart attack released include in those in response increasing a heart attack People risk. The fat the to the John figure, borne of food is much for kinds I don’t the the CDC quarter incidence to the dietary supplements? food poisoning fatality the use is the the information. expressed Version a noradrenaline that can cause which be foods. be a the the far use CDC population of has sources a food- today is for high- is a fair number to say for alkaloids].” approximately food poisoning food by thousand 60,000,000 to each -- year How consumers. bacteri-al food associated fatalities is equal U.S. to poisoning with per ephedra year about does from one food three years with per year. This food consumers. 21 deaths number to is my area, infectious fatalities in the need would “...if of our of all associated or about supplements, the over 7 deaths of people numerator. using ephedra What is supplements day? members not trigger data. 238): caused 30,000 found denominator, had and preparing that associated-but-not-necessarily-causal The FDA per of ephedra on any given fat, to attacking disease, from of Nine poisoning FDA has pg. that third incidence bacterial than [the ephedra fatalities compare The and is and and doing if that suffer it of poor from know to one of be 30 percent estimates Americans one II disease of compounds 80,000,000 about (Vol. food-borne Indeed, and aggregability, clot in using on the basis 20 to than funds for infectious that risk population, could public Guzewich you know, at risk platelet blood safer careful FDA limited disease, these the products J. increase of an abnormal education herb food and a attacks calories, meal This ephedra from heart excess deaths or stroke. think use people Alkaloids illnesses, a heavy so as to be more better serious for educated is more Ephedrine are 9,000 uncommon at the risk there deaths, food-derived is not Containing alone, the in many from It Supplements contamination occurring cholesterol. thus ;Dietary of even The grave the committee attempted transcript concern of 12 August, about to were supply of the the 1996 the FDA’s 1997 4:1OPM very PDT; concerned essential Food lack page Advisory that denominator Committee of a denominator: 9 the RE:Docket No.95N-0304 Dr. very Hui, Vol. useful There’s II pg. for professionals us by nothing ;Dietary Supplements 61 but 11..what you these are and it’s scientists that’s Containing really safe. have Ephedrine put literature used I think together is written to treat it’s Alkaloid for diseases. all risk-benefit ratio.’! Right. That’s why the denominator information is very important. Mr. having Appler, a conference Denominator under the that Data. can’t knowing what Dr. safety the agency Vol. this, way mean, and us your and poor the essential we Version to and do filed concerned . .. without see OTC is called be is Dr. Kessler convening with an regard to we are-l! denominator to get at that decision data I pg. for--I issue of judgment without mean, safety as of on which Vol. 1997 of what on necessary the such meeting, time which 4:1OPM 276 and in they~re to go out PDT; to [data] the my exists.” basis of very by the FDA. The information, such and that it can then been 10 can FDA as should hold render a an Rule. talking assessment page consider a scientific an informed “We’ve in you Committee, the FDA can base II pg. data, can make provided to until serious denominator people ask Americans data, denominator, of 12 August, telling scientists to provide no safety “ ...1 information Committee but some the predictions.1’ in light millions Rule we have predict 161 that Marangell, and to magic, proposed ‘!..yes, a numerator back denominator informed numerator to enumerator what the to validate Vol. in its duty properly the to 161 have safety quality its Dr. have 1’1 don’t FDA a topic center ephedrine is try coming best withdraw informed what I pg. trial affecting failed is Vol. Kessler, has of and yet here I can The FDA expects little the 132 as on of advice.!! and do a clinical judgment pg. center injuries devices, advice then us to predict [giving] of address compounds, seeks any II to seeking only but--I Dr. medical device September are.;! events, asking of the denominators Dr. Jasinski, of 21st meaning issue the “Your the group the 81 reports evaluate of these that’s for a meeting advisory the Since Ricaurte, organizing II pg. on statute it “NOW Vol. of about this I RE:Docket agree No.95N-0304 the data is very Dickinson, needs to ;Dietary Vol. be able denominators, as Containing Ephedrine Alkaloid~ needs information, poor. ..“ I pg. to Supplements come has “Industry 284 forward been with mentioned more by more information several on the speakers here today.!’ Some denominator the committee Omnitrition Vol. has ephedra-based market is market a assume servings have year I would servings, 100 taking this allowed understanding people of million people, about and that’s Dennis users year for of ephedra-based 29 you mean Now, one the million real people reactions II 30 estimates with who are is ... more have used two who at of the last on five takes a control II. ..our me is a 50 are what should be is taken?” estimates, the using order what, people drug to actually billion 200 million for take some the out one million respect on the say means question before pg. States or in move the of products.” “Although average percent over may number in of ephedra-based of perhaps point our the 10 to 20 last five supplements.;f I pg 250: and a half II...the doses from the health Vol. herb. 10 to that’s which Jones, of this percent, servings if you consumer Vol. just 5 the who a million around 10 percent, years, position that ephedra-based Ford, our guess the supplements that that Vol. dietary Mr. during five million five years, in the United years 10 past over adverse Betz , it’s II pg. sold one to have Mr. by industry the 100 probably assume Vol. drug. of percentage “Over believe small, it’s been 27 We servings Ziment, and pg. approximately If you one billion Dr. to sold relatively and years, II products. share. limb was provided meeting: Betz, Mr. information II pg. but per day that we have [of ephedra used is products], food stores.” My estimate 12 weeks, figure 277: II..the enormous is 5 to 8 million other people have number Americans four times of each that estimate. “ Commenters containing serving, Version Pearson whole ground adjusted to of 12 August, and Shaw ephedra contain license herb 20 mg. 1997 4:1OPM PDT; a dietary (about 1.8 gram total of page supplement of herb ephedra 11 per alkaloids RE:Docket per No.95N-0304 Their serving). conclude that containing and H few the 21 ephedra common were from high, by common and, supplements ephedra 7 there of of ingestion and same M are many of number of to ten times other in alkaloid were containing from food incidence the 21 deaths alkaloid of foods the closer that deaths supplements as of ephedra is probably ephedra 1,000,000 consuming the the as all dietary causes (besides consuming foods in the lowest which industry would estimate, result ephedra associated this 33 in a deaths 1,000,000 worse per users case year on incidence per million users. Compare per year to per million Even definitely if ephedrine the by (which dietary most of labels (15 already 4 to 5 times bacterial which safer of than that deaths has ~ require dietary caused Version of 12 August, also from 1997 does the not contain contain which food with deaths ephedra according of which no in common food the label contend), the up mg. to 110 with the warnings) incidence anaphylactic doses were are form. death not to caffeine) provide excessive figure reactions, of calories, fat, causes. delegated supplements used poisoning, and not other and cholesterol, poisoning certainly (some food cardiovascular when FDA percent remember Moreover, food associated ephedra the extant Congress deaths supplements and to bacterial food users. all caused instructions not of ephedra from at on any day. actuality, evidence poisoning) day, estimate: refers In alkaloid given supplements form to them industry: result about led form. given extant be supplements. those using a in common of course, food are Alkaloids ephedra to of deaths would foods of the Ephedrine has supplements dietary cause ingestion Let us take any these containing there market of actually is no compelling the the consumers people were only Containing is similar consume deaths these supplements bacterial of 212,000 dietary there caused as then using in representatives consuming containing people by the form, deaths number alkaloid poisoning experience Americans as Supplements supplements meeting to 8,000,000 ~ the dietary Committee ;Dietary authority to be safer 4:1OPM PDT; to than page FDA food 12 under DSHEA in common to form. RE:Docket No.95N-0304 In this rulemaking, authority by dietary requiring is a supplements. The vires 1/2 of the to the Vol. pg. containing dose over to dose one reach re-propose a new Rule. 7. more the stringently than Committee fly in the is according also a FDA the products admitted consumer was analyze them. consumers VerSiOn for in Hence, which of 12 August, —————__ ephedra any other (perhaps noted [ephedra build on alkaloid certainly up to increase Gissen are 1/4 to not the full not possible to do limiting dose and the building up the the from the Rule, corrects regulate common in one re-convene the this and error, dietary form. the to use its supplements FDA Ruler has and a standard burden of done re-convene that proof, unreasonable reporting to does not obtained time they had adverse very of no reports 4:1OPM PDT; few the way reactions were were page They to do so. samples know made 13 used For incident to that when instructions. but did not attempt show or abused. adverse label to risk and not misused the 1997 its to withdraw consumers at an gradually people that and according using because of Congress. met it had FDA’ S rulemaking dose consumers cannot foods for this, that for dietary using and limit that’s instructions, assumed safety form. As Adam want conclusion significant evidence you it must not size) use, instructions has to label example, provide with FDA ephedra hence of (or virtually statement FDA delegated against when a low withdraw face of the will 8. using a new proposed dose to discourage DSHEA, this, that label Under precisely try must Committee, bias of use. to two weeks, FDA FDA’s with supplements] will slowly. of serving yOU proposed week common Alkaloids the APA. level something 10 days in supplement single “If standard food this is to begin dietary week. 1’ FDA’s use dietary Ephedrine its Congressionally establish suggested 38: take withdraw to suggested the dose to for Containing higher expression way of supplement) going than and violates containing II much clear safest alkaloid a FDA must it is ultra Supplements the FDA exceeds supplements rulemaking kind ;Dietary must The FDA of what in order whether were the to those following RE:Docket label No.95N-0304 instructions whether they Dr. Lori cases Love what Mr. cause were ;Dietary Supplements or abusing taking a consumer these ephedra themselves, so we could Love, and we actually samples where consumer was were reactions at do in many the II pg. 119: “I do not have that data been able to the time the over only collect of l-to-5 formulas is in there?” we’ve at have else analyzing which dosage, what ll...we have using formulas, low you 107: Vol. II pg. of the Love, Vol. form because, where we’ve using at Because been the of standard 107: serious per the that in hand the weekend.!! a relatively few sample the injury and I’Dr. Love, adverse serving as to how able that be I have events able to many of a question below of the ephedrine those time of FDA re-propose a new Rule. People on the ephedra the median alkaloids, out of herb ephedra is unavoidable same the available attack may buy engage in an intense know do total of 12 August, ——— as exercise 1997 have due many people shovel one PDT; to this error, the who put common are eat and drop page 14 dead. and conditions etc., may however, in place and at risk a high the conditions ignorance, you was that.’f re-convene of in mandated diabetes, other snow, regimen, 4:1OPM analyze contraindications, regulations and to corrects what to the consumer Rule, hypertension, For example, a shovel the that they that data few samples Congressionally misuse applies products. the our relatively able Some no matter problem be withdraw disease, herb. only and meet labels expressed the sample conclusion don~t as cardiovascular use to must a new who we have injury failure proof, We haven’t to collect reach 9. 107: of course, this of II pg. Committee, Version —.— time. events: Dr. the even same verify ‘1...on the II pg. a percentage adverse still 119: Vol. in terms have such at the identify just of 20 milligrams given or Alkaloids that.” for you, that as cocaine alkaloids], Vol. Dr. Georgitis, you supplements 149 1’...we cannot II pg. adverse [of Dr. Love, II pg. Vol. serious Dr. Lori such the Ephedrine used.” milligrams value drugs (FDA), Vol. Israelson, “analyze were Containing and widely of heart fat meal People or who RE:Docket No.95N-0304 don’t know foods and other mechanisms. those they of conditions, list small and rather any of which FDA the an has at Advisory OTC pseudoephedrine, from and they we~re dietary and response that anyone going to containing Version have could be However, without we favor shield type so in the education consumers for for for their actions. the them, 1996 participants the to use for to thus meeting ignore of of the ephedrine which products from consumers thinking with (Vol. I includes weight pg. They loss) , from in OTC. the OTC follow up after all, “Currently, So, what market? Would in being similar also alkaloids, from ephedra?’1 Yetley on are, 47): are used is banned derived focusing This OTC they responsibility during phenylpropanolamine the market? supplement these Fong if ephedrine Elizabeth really used product.11 products, OTC be of these why their associated as one or more long they the not warning dangerous points drug H.S. are also Dr. all and it. is and phenylpropanolamine pseudoephedrine removed so is told (in Harry happen only sugar and ephedrine. pseudoephedrine would this responsibility several phenylpropanolamine Dr. done reactions in using Alkaloid: conditions realize a you have that high should not to read It Committee of adverse OTC may That risks. eat medical for personal representing FDA FDA glass Ephedrine glycosylation Perhaps made room from taking The alkaloids be the OTCS) product. consider them Drug issue of that 10. is one before can to be some the to excusing buy chronically conditions. a magnifying has than believe fact for Containing hyperglycemic containing warnings use need the with label medical need There the via see a physician of you sale a may “If you are not sure whether added: the diabetes People ephedrine those Supplements themselves on (including one have damage given ;Dietary (Vol. today I pg. is not 47): the 1’1 think drug that issues, but what the issues.1’ of Dr. Yetley can walk products of 12 August, the on the 1997 dose basis 4:1OPM FDA evades a supermarket containing restrict products into of the ephedra or PDT; drug alkaloids. length of or the of safety, page use it 15 is of a important store and If the FDA ephedrine reasonable RE:Docket No.95N-0304 question why these be restricted. of ephedrine (Note, the containing of content again FDA. used that provide do not consumers for may some at alkaloids than Dr. Irwin huang and give effects that are drug sought using Vol. I defer will without a were (Branch alkaloids or the issues or the bias on the dietary set doses many such ephedrine perverse plus result of that ephedrine that of 116: comparable on Love, the side on a year-to-year ephedrine 116 “I don’t Drugs on basis products.lt have [FDA] this is of ma “...Dr. information even there the dangers dangers pg. more data of FDA) total containing l’...1 feel II from no of dietary FDA doses the II pg. people of products on the legitimate to much the consumers, a lot about recorded, are political ephedra bit (FDA), Vol. there by Drugs by 115: Vol. little drug. supplements. knowing Ziment, as have higher II pg. as containing OTC with like times question energy in the dietary reports Love There up actually Unfortunately, OTC did us Dr. Lori supplied or available end Dr. can and loss in that we are hearing perhaps in adverse the 24 mg. ephedra ephedrine dosages, Ziment, drugs.” 6 phenylpropanolamine ephedrine orthodox to may they if benefits higher consumers a disconnect the or theophylline to typical up also phenylpropanolamine alkaloids a brings weight turn pseudoephedrine of Moreover, supplements 3 Alkaloids not contain a caffeine and about Ephedrine would OTC products phenylpropanolamine This the effects, of theophylline, contain alkaloid supplement.) some pseudoephedrine or Containing similar that 120 mg. products ephedra Supplements with too, OTC pseudoephedrine part others, plus Moreover, ;Dietary that on data that.11 essential subject at the meeting. in whether ephedra the alkaloid FDA regulates containing the dietary supplements. Dr. Jasinski you look much at the greater estimate, as it’s and deaths. Version DAWN data a public pseudoephedrine shows (Vol. I pg. two that health ephedrine, when the or three Could you yet you DAWN data times the 1997 quoted, problem, you go through of 12 August, Ilwhat I don’t 99): 4:1OPM two is if pseudoephedrine to three control, which was incidents used and that?~l PDT; understand page 16 times you for was by my exempted the emergency basis rooms RE:Docket No.95N-0304 Frank Wickham (Texas “Yes, Dr. Jasinski, based upon (Such the ephedra political products would Then, stores stores pressure money cynically. Mr. the politics Here marketers the a drug stores I pg. the OTC recent sale trade past of of the dietary pharmaceutical FDA without alkaloid be upon in DSHEA oriuinal to the bear safety dietary 99): of supplement “...the health products. their money if you II...1 think is concerned, has of containing an food The drug by selling want to look at that is part of alkaloid supplements interest dietary must impinge concerns upon OTC carefully products. its and in is no FDA bias containing might the supplements We there explicitly between alkaloid products. that stated yes.!l ephedra cold ephedra toward In the that the the sales of the Committee drugs. must withdraw suppressing decision brought 100: to be sure FDA will products, offering FDA policies and conflict pseudoephedrine-containing examine * ~ politics?ll clear of ephedra ~ make cold Vol. see sDonsor (Vol. I pg. as far as the market we 99): decision ~ and pharmacists Is this Wickham, ~ political ephedrine-containing pseudoephedrine-containing this ~ I pg. Alkaloids and capricious.) said selling the Ephedrine of Health) (Vol. standards in OTC products be arbitrary with can different Dr. Jasinski make upon Containing added) Placing alkaloids Department brouqht (emphasis FDA. Supplements that was g result pressure lecrislation.” upon ;Dietary which the Rule extremely considers and re-convene relevant this information, essential data, and make a new issue a new rule. 11. loss who or energy) will take knowing limits as Reducing how they will more much dose to to should government them an effective in increased try respect) perceiving below result they should l~fakel~ or warnings, the get take and, the as to be risks one may equally the of 12 August, 1997 4:1OPM PDT; 17 people seek the (not daily instructions ignore Ilfakell or page or use well. Version those they serving also (for weight for results perceiving propaganda, level not the safety useful as RE:Docket No.95N-0304 Many consumers familiar with consider the consumers is to credibility the FDA’s this, FDA choices must if the dose to ignorance among than the a source surely fall Rule, corrects of more answer but, of FDA The on FDA’s whether information. on deaf ears. re-convene this consumers alternative rests reliable ‘Ifooll’ and a perfect consumers that maximum not education millions the and will supplement will may with people. withdraw a new conclusion the levels It is not on and message, of them “advice” like Better answer. dietary consider government low it is far better impose to consumers reach best FDA be to be ignored. considerations. society, attempting to be, answer by Alkaloids will especially arbitrarily the Ephedrine products suggested something to not is the in a free of are perceived safety information dose herb consequences, dosages and the Containing ephedra a misleading disinformation, Setting not, label lethal use period using above entire contraindications Supplements already doses potentially about ;Dietary error, the If Because committee, and re-propose a new Rule. 12. Caffeine of caffeine found 1984) bias in adults. That must in toxic withdraw a new conclusion dietary that in is about 10 NO-DOZ Stimulants,” OTC ephedrine in overdose the Rule, is free JAMA as is (Pentel, 252:pg. (120 is caffeine. re-convene 1 gram same tablets. products than than the the from arbitrary supplements-and We have ephedrine, examined published phenylpropanolamine, to the FDA~s proposed 63, 67, 68, 69, 70, 71, 73, We concluded with or of greater 1902, mg. per Because Committee, and capricious in favor of OTC drugs, reports of adverse and a new Rule. 13. exhibits doses coffee theophylline against Oral Over-the-Counter FDA re-propose with of is even more this, reach cups of The tablet) of may be toxic in ten “Toxicity toxicity: that most and pseudoephedrine rulemaking, including 56, events that are 60, 62, 100, and 128. of the adverse events were associated abuse: Reference Version 68 concerns of 12 August, 1997 a 28 year 4:1OPM PDT; old woman page with 18 a three week RE:Docket history and No.95N-0304 of ;Dietary progressing orthopnea. for 8 years She shortness admitted to try she reduced tablets, after which her of 25 mg. of ephedrine overdose; it is possible congestive been an 67 concerns heart quantities clear of ephedrine immense ephedrine psychiatric 80 tablets This onset this to 3 80 tablets is an immense experienced why of woman by users didn’t die after what dose overdose, old ten developed taking large compounds for energy. It using it appears as she was years who of she was cough housewife but taking medicine three daily to have bottles at the is of an time of who was He had referral. Reference a 66 concerns cough progressively mg. in part containing containing drinking tolerance tablets the worsened. Alkaloids fatigue, before (!) a day. the cough, ephedrine from rapidly a 32 year failure exactly taking intake symptoms at least 25 mg. One week daily that dry Ephedrine so much. Reference not taking is 2000 mg. explains from taking to her Containing of breath, to lose weight. symptoms of ephedrine Supplements a 36 year medication increased more than old insurance containing his a bottle ephedrine. ephedrine a day, agent intake each of until which he was contained 400 of ephedrine. Reference 69 intracerebral “speed, “ concerned hemorrhage containing substitute for had IIspeedll in used composition revealed illicit of the a 20 after year taking old man who an unknown ephedrine. It was drugs, as amphetamine. the pills, no amphetamine, such past but though clearly did urine not drug methamphetamine, suffered an quantity of used The know screen as patient the on a exact admission phenylpropanolamine, or caffeine. Reference had both pills used (each consumed Case 23 70 concerned large pill three quantities contained case of the 15.3 pills (150 mg. 2 had consumed 10-20 of the pills unfortunately Case for 3 suffered its victims, events, including Version of 12 August, exercise a same mg. 10 of the years! reports. PDT; 1 and (153 to 306 reg.) daily for berry from all Case at once result and emotional containing ephedrine). of ephedrine) can one and two ephedrine of ruptured 1997 4:1OPM Cases aneurysm many excitement. page 19 which, commonplace RE:Docket No.95N-0304 Reference become ephedrine 2,250 dosage (450 mg. of ephedrine during days he had over 26 the past a job ingested each year five old to her 30 mg. the hospital, twice of developed he a night) total before of asthma. who The days taken man to had (a total of her tablets three to have day Alkaloids who 20 years, a in a bakery. in the woman containing times admission (30 mg. holding Polish exacerbations a Ephedrine questioning five before ephedrine while old under ephedrine) concerned Three awake year Containing of up to 15 tablets, 82 taking a 54 admitted of ephedrine!) psychosis. Supplements of ephedrine mg. Reference started She quantities recent keep concerned psychotic. increasing most 86 ;Dietary to amount admission of was 750 mg. Reference taking a daily several weeks restless and personality using may have herbal of using and clear, been in this huang herbs even problem. with fresh other be Ma huang human dietary before used in the problem having the FDA, of old to get experienced ephedrine he suggests that greater the be was it than developed ma huang. associated in Pearson and or may fields require before of matter grown oxide, who use plant of their do this woman uniquely Any ethylene have the ionizing licensed sale, the (and many raw herb radiation products. even ma fertilized Shaw that with if it Most is not order. Americans strawberries, at year with may manufacture in the purchase imported 33 a problem heat, he been After began substantially formulators) specified as a Commenters suppliers of and loss. he time, had instructions. Asia feces. with number amount who weight ‘~greater amounts!! in general. herb newspapers amount association reputable A The is not man amounts,!! mania. supplement sterilized for that the from old At concerns Unfortunately, or supplement in the label hepatitis year sleep. but 128 45 ‘Igreater an excessive Reference a diet couldn’t recommended acute concerned changes is not that 100 were recently reported in national developed hepatitis as a result of causing something of a relations since the public public blamed the FDA eating for the problem. Reference Version 56 concerns of 12 August, 1997 a 14 year 4:1OPM PDT; old girl page who 20 took 15 to 18 RE:Docket No.95N-0304 capsules of a ;Dietary mg. arrhythmias her total 15 capsules, caffeine (doses toxic), of controlled changes disturbances in were safe hypertensive trend in the a drug which The has and present If dangers.” Reference evidence however, might heart chest pains containing Version three 50 mg. of 12 August, is a very as of to three first after said after an not taking intracranial letter that neurological abuse or illustrate only an of 1200 mg. the addiction. its in amine, low potential dosages, frequently. patients that after case, developed a 24 year ingesting PDT; page clinical ingestion acute a phenylpropanolamine, 1997 4:1OPM was made sympathomimetic available more had but of of of significant.” produced weak an upward population (a total end The effects show who with a drug serves injury hours girl some controlled larger 60 mg. rarely in pseudoephedrine to hospital the Mild detected. did previously at that statistically significant old diagnosed be abused The phenylpropanolamine. a admitted becomes 62 concerns of was found medically studies 17 year status ephedrine pseudoephedrine a only achieved case, be medically retention to be clinically note it in release in which, was authors Because not our pseudoephedrine has complications. of may parameter. statistically rates, to symptoms of 12 months She pseudoephedrine) “Pseudoephedrine more authors urinary majority concerns The and may prove containing hemorrhage. took 3000 mg. or result sustained without abuser. not significant “while at self-poisoning 20 tablets of only patients, The cardiovascular pattern or heart 71 she sustained-release taking did any parameters Reference to be the for these of cardiac If risks congestion. in patients hypertensive attempt nasal that pressure developed mg. of mg. recovered. 1000 mg. 50 of ephedrine, of patients sleeping concluded She potential administration significant appears 375 mg. concerns for subjects she alone hypertensive “pseudoephedrine on blood was and gesture. which 25 Alkaloids of phenylpropanolamine. 122 pseudoephedrine authors dose caffeine and 750 mg. Reference male from as a result, Ephedrine tablet) caffeine, of in a suicide phenylpropanolamine, Containing (per containing product 200 ephedrine, Supplements 21 old single 4 woman of had capsule mg. of RE:Docket No.95N-0304 ;Dietary chlorpheniramine, and to be considered that than the Cases 0.2 the combination eight taken were phenylpropanolamine, who of 8 mg. ingested of for her containing was a approximately and 31 2.5 each 200 caffeine. of of mg. of schizophrenic 40 tablets, mg. two had mg. and old ought injuries. 50 year Alkaloids rather Patient of abuse. chlorpheniramine, three It substances, responsible cases Ephedrine alkaloids. of these each phenylpropanolamine clearly containing 50 This is abuse. Reference brought to 63 the associated contained 75 mg. The amount total not have a old two was history of She been taking taking of was taking and not history which that of caffeine. This specified. with of was capsules 200 mg. a sympathomimetic was dizziness, hypertension, was who palpitations She had no prior of phenylpropanolamine she woman tinnitus, breath, medication. black episodes to stand. had without year of inability but 43 after shortness and controlled a hospital disease, should concerns with diaphoresis, heart clearly Patient isopropamide. mg. was capsules Containing of belladonna mg. phenylpropanolamine, two and three woman Supplements woman her history of hypertension. Reference obese woman, symptoms concerns was admitted after The patient drug 65 taking experienced year any drugs old prior along drank man, to admission. hours prior caffeine, to to a grand with three to blood alcohol This man eventually high dose alcohol, mal He had taken was 5 mg% died along in with the identified caffeine, Version as 200 man “pick-me-upf’ mg. of 12 August, of 1997 doses ingested legally This two PDT; three been a 26 hours to four 200 mg. drunk of combination and 22 200 50 of ephedrine, patient capsules, containing page level). The third black ephedrine, 4:1OPM eight of caffeine, abuse. capsules have of phenylpropanolamine. the drug No patient, whiskey hospital. high who old second of and 50 mg. was year The she might contained (5 times old “congestion.” capsule is clearly 17 for capsules Each year at the hospital. whether ounces 18 neurological two black and phenylpropanolamine a seizure an with Comtrex R of six One, hospital the Comtrex. of ephedrine, His the tablets admission. 25 mg. patients. so we do not know scan was done, using two three later mg. mg. of of RE:Docket No.95N-0304 ;Dietary phenylpropanolamine. Reference reactions This 73 (ADRs) is a 1990 been reported America. Many such cases legitimately [OTC after ingredients, or PPA was of PPA of were severe. compatible common with PPA 142 this 1981, a adults deaths ADRs in company reported time (1990), three FDA advisory another study cited for hospitalization risk or using who had 60 factors a heart sympathomimetic reach consideration FDA claims . suggest FDA a for may new the must withdraw information 1997 upon, in the prescriptions of no known of heart disease, pseudoephedrine. normal the corrects in the adverse page In alcohol, that PDT; paper drinking Rule, and re-propose 4:1OPM this used coronary “pseudoephedrine, implicated conclusion to depend of 12 August, be most with of had that million incidence man history he in or stroke. of smoking, that that to be safe. 200,000 60 mg. be products 9.5 of PPA old PPA fifth increased year taking showed agent, no or family after authors spasm. ..“ Committee, Version attack The coronary drugs, the are should that arrhythmias, 28 associated mentions judged of over eight reactions using had and no history examination arteries. a were paper PPA ADRs the most publication found concerns recreational Subsequent that products After headache the a review for hypertension, Reference cardiac of panels here, PPA-containing making An symptoms underreported) research the drugs. cases. adverse this At U.S. combination hemorrhages, of consumers after involved due to stroke) aids, 15% 85% [reported] severe In fact, diet attributed only the period. OTC in North products, of the effects possibly 1965, additional of discussed of millions 25 year the PPA intracranial the (though using 82% with (mostly While with side Twenty-four marketing were amounts, “Since contained a third hypertension, to the tens during in about drug Of ADRs versus often along frequent ingestion.” compared consumed most acute product adverse 69% of these sold Alkaloids and died. 1965. go unrecognized. PPA non-overdose The since of OTC products taken and eight serious, drug was complaint. seizures, with The Ephedrine reported prescription] consumption drugs. ingestion of in 85 studies, may or prescription overdose review stroke for phenylpropanolamine have occurred Containing man had a large 142 ADRs to Supplements initiation re-convene this of the lack reaction a new Rule. 23 a of cases RE:Docket No.95N-0304 14. light We have of the paper Reference 43 Suspected Drug ~ ;Dietary Supplements considered on how data Reactionsls presented to evaluate ~~Approaches (Jones, Post-Marketinq the in Strom, Surveillance, Containing adverse by Evaluating Velo (eds): York: the drug to New Ephedrine Alkaloids FDA in reactions in Causation Druq of Epidemiology Plenum Press, 1992, PP “ 103-113: The assess For limitations the degree example, Requiring Table event could For of caused example, and effect the attacks Naranjo provides strokes using in the the not provide Committee on this background it virtually adverse the events background incidence. Food Advisory Committee know that whether occurs.” (Such cardiologist Lake children The the says FDA has consumer substance may not be what used the example, Version for is Dr. (Vol. when the instructions, of 12 August, the of same at “,..we as the need to spontaneously Michael Vincent, a in Salt 8,000 sudden, unexplained deaths it has A FDA the 210) product was appears 1997 4:1OPM information who is inappropriately simply to little consumer about I pg. which events, of Medicine truthful Love of incidence than G. Advisory School taking according greater products. year.) that The millions noted 119): as of Utah took. took. product any example, are example, perfectly they reported label admitted M. (Vol. II pg. each actually (by, asked are and adults the Chassy For there whether Bruce exist. that types As incidence data these or about meeting events Food or lower Dr. which confounders. containing higher at the University City among was know the versus causes such the Data about effect to of to of of of probably alkaloid to and refers incidence level Types alternative information impossible reported cause population ephedra did and to association. 10 questions question is a background FDA making of difficult mere Algorithm to assess This it very versus 5 is: I!Are there event?” and make a series can be used there individuals The cause Question have heart data 3, that association. FDA of Judgement adverse of the this label said “And apparently to PDT; be in page abusing large stupid assumed on what doses) behavior that the when consumer instructions. the adverse used the 24 For events according majority a of to the RE:Docket No.95N-0304 individuals where on pg. Vol. II verify that mean that’s that they we have 120, a very an believe There Supplements evaluable Dr. or any other took you would ;Dietary Love data.” says you that question. over-the-counter Ephedrine (emphasis “Are information difficult Containing added) asking if our patients If the product on pg. told X value to verify II 107, few samples where consumer was analyze that.” could not (as, for dosages This Dr. we’ve using Dr. the dose Love the how the median fall very broad range of very median. deaths. or This Did they much high claimed about there and the standard deviation. Moreover, Jones “.. .a fixed work weight loss by indicated defined and most only 86 have proposed get new their Version followed rules. rules of 12 August, his in Europe FDA that the took per had and doses during because 1997 is being treatment necessitate reactions, stopping information of 4:1OPM the PDT; the before page effect to 25 on the It would average based mainly approved for by many as Danish data which were therapy, issuing in a big not a small out period. ..!! The FDA was political, have (Vol. I pg. touted available. a two-year that been not do the the combination adverse does respect supplied at Naranjo levels? has FDA serving). A a large with to place eg., to the committee which We suspect had the able or do they dose colleagues up on this out high reported reportable daily that distribution. have Then be of doses, important if the effective as reactions of 9.6 million should and indications safest could 149): relationship events average ephedrine/caffeine Astrup 107) milligrams the at especially useful Dennis sample dose-response 20 to a relatively and II pg. a bimodal dosages dose the more the injury adverse of only answering question 8 of the dose-related?” A median amount been on the the value have 275) that the particularly occur the (Vol. on of range is is of on the distribution in a narrow percentage the information II...we have admitted many important for IIWas reaction Algorithm: doses you [dosage], consumer to collect time information example, any says able the is provide Love been at provide below I them.” is a need Vol. can us? take. However, Dr. Lori Love of the FDA noted (Vol. II pg. II...we cannot verify in many cases what a consumer used.” . Then we give patient at Alkaloids their rush scientific FDA to or RE:Docket public No.95N-0304 (heated are FDA extracted added it on so of Question adverse drug on proof available at suggested it, how you you outside from supply Then number Version we of compared to the herb. “Did reaction (Vol. that of the that job of without re-convene Rule, corrects FDA reported poor the I pg. the association withdraw human the meeting mere conclusion to were II people be in the Advisory of on Vol. an awful poor additional rush quality Committee II pg. a report meeting this error, to get these of the data would information, to And, strongly as have and submitted we this data have you it to at 196, Dr. Kessler agency 4:1OPM this will PDT; over work page “I intend have to or report review?” to do weekend meeting hard 26 the the and agency a peer committee says made, the taken Love: collected you’ve within even Dr. you 158) : “We, of course, you the asks how conclusions to 1997 data, similarly, analyzing of 12 August, your review (Vol. II pg. that on internal committee pg. 158 Dr. Jasinski it and what this information Vol. and put in extremely an and when Love 4 percent a a pot for ephedra Dr. as into it, asks: But have comments. agency? answered the on Drug prepared ad hoc but as whole Committee when interpreted the Dr. Love a new huang is prepared Algorithm done alkaloids used absorption ground FDA must seems submitted this that, hence ma manner might evaporated a tea only ephedra products the it, usual consumer a carrier causality collection you on in has issued, the example, II. ..have put faster Advisory FDA in these For much rechallenges FDA rules the Alkaloids a new Rule. proposed suggest how Naranjo Food reach The 15. huang re-administered?” of causality, and re-propose ma boiled swallows between Committee, the FDA extract the events. discriminating the get a person at the reports Ephedrine in the of the much of is not you of how water, That #4 when stated have and tea how much case Instead, Plus when reappear Containing a ma huang know the a concentrated absorption 202) to in a carrier. form the as methanol ! prepare to determine tea. consumption has not ingested traditional and did in a pot) actually Supplements considerations. health, The ;Dietary here.” promised get to to a a RE:Docket No.95N-0304 decision soon after about the report What the FDA l’intend[s]” part of the not “intend” rush here advisory do it. arbitrary more than One now Committee, reach political a new not FDA, whatever is supposed to be the judge Analysis There the report the American medicine of inadequate Michael Rush director of commissioned underlying 191 adverse Clinical these Summaries at Tab events at the he categorized events, Food that for information, lack possibly report of related, to the transcripts. summarize his for questions. Dr. Davidson also evaluated Version 13 were and on Vol. he had The ought sort to another of have by an independent of 12 August, 1997 4:1OPM and Research. five 4 minutes detailed Of the 191 the scientific group. 27 unknown were Davidson’s the meeting minutes were breakdown by events, 22 Dr. of Event all 8 were 59-69 page the case of serious performed PDT; Center, related, about 3 or careful, been 84 of of analyses related. only fellow professor meeting. the I pp. consider (see Adverse remotely is Then to and to ephedra, probably Unfortunatelyr report. Of 7 were Committee considerations. detailed Committee were not Congress, to review summaries not related 34 Rule. to the science, for Clinical 84 as serious. he determined on Medical by the NNFA Advisory FDA re-convene assistant He gave F). longer meeting Luke’s event as is required a physician Center was files the Cardiology, Dr. Davidson in Reports at M.D., of the Chicago the influenced no of time a new Events Presbyterian-St. of M.D. time Davidson, College at medical was of Adverse is of political Davidson, does Committee politically is based re-propose not a FDA some the the Rule, that said FDA has behaved Kessler withdraw and Michael 16. their added) were the least using amount conclusion considerations, at manner, David FDA must do the job correctly. Apparently, that Alkaloids Dr. Love review considerations. that FDA can take Commissioner, that and peer suspects a fig leaf to cover Ephedrine (emphasis review comment. and capricious Perhaps decision. report for public Containing committee.” and the peer to do? That record to this Supplements is due to political a grossly little ;Dietary FDA, to allowed done too, by and RE:Docket No.95N-0304 Michael ;Dietary Davidson, Dr. Davidson’s the Chicago is the drug, and that of more occurring during the Foods received by evaluate the the FDA on and Dr. the the whether states reactions the adverse National event reports products are food, investigator by dietary they the Davidson “retained to review Davidson adverse ephedra-containing ascertain for as a principal was of Dr. trials in evaluating He recommendations associations and supplement based to trade on appropriate rationale.” Dr. Davidson reports based Adverse (Vol. I pg. on Event standard members’] case underlying files 191 serious case and 107 not that unknown Summaries 191 I found to be serious.” 13 were not related lack of 22 were possibly at 84 of “Of the to ephedra. information. Tab event event reviewed F I also adverse categorized the adverse “I have In addition, of these for related; criteria.” materials. files, ‘II evaluated 60): FDA Clinical [Committee found trials. Alkaloids In addition, of which industries. trials Association above. clinical experience 200 clinical Nutritional these products Ephedrine 59) : Research, performs 10 years’ Containing are cited Clinical nutritional than medical for director, he has over (Vol. I pg. qualifications Center medical M.D. Supplements of the your reviewed the summaries. the events Of to be 84 serious events, I classified eight Thirty-four I as were remotely seven were probably ‘lSix deaths were possibly related, and related.” Dr. Davidson associated provided with @ e~hedra. consider consumption @ six possibly deaths sudden death all three were due [error ~ toxic doses strokes. individual who had was a fatal internal cases, ~ carotid with of of This deaths due to on autopsy in due that multiple other occlusion. of 12 August, 1997 4:1OPM ——. .—— were be stroke] on in a 44 year PDT; She page to — “Of the associated was atherosclerosis occurred artery present had 28 to deaths a in supplements female a strong occurred autopsy. old M related added) three possibly who was using artery were (emphasis were should information deaths ephedra, the these enouqh ~ eDhedra.’l Two One that ~ abnormalities male basilar stroke ~ 61 associated and cardiac to pg. assessment. individuals. and VerSiOn I ~ in transcription. an obese left Vol. very Another due to a strong RE:Docket No.95N-0304 family history individual of death Apidex, associated Containing sixth from was possibly a seizure drug deaths Ephedrine associated was for weight occurred Alkaloids also on Al 1 10SS. on the high dose products.” “There were ten cases ten cases, four, these The a prescription six possibly ephedra Supplements strokes. whose phenteramine, of these ;Dietary ephedra. In another provided myocardial infarction, to In all three angiograms were my judgement, an of these not there In high-dose not three enough with of ephedra infarction arteries. ephedra to cases post-myocardial coronary Of related was association reports, normal infarction. were assessment. possible consuming myocardial reports, make a revealed individuals in three information exists. of non-fatal All ‘ three in combination with caffeine. “ ‘lThere were were unrelated products. In available for cases, reports or remotely four me four individuals to of prior dilated left remaining the were lupus associated cigarette over but on oral with smoker, and before a positive containing history of were 16 remaining ten products exists.” associated case of source premenopausal the of these suffered as was use of on the seizures. Of two of noted as having a possibly and one was on the product being the high-dose a for hemorrhage. exception a The was remaining intracerebral inhibitor --were emboli. of these was with At least is unknown women patients --the a male diagnosed three these hyperlipidemia women. One other cases, involved possible In reports seizures of seizures a neurologist, Version stroke the All woman ephedra products.” “There majority she lupus a One contraceptive one was In ephedra cases information hypertension and the inhibitor. of these with Three ephedra-containing enough contraceptives. smoker oral to evaluation. stroke. as strokes. not possibly involve cases, a year one the cases to be a cigarette positive cases, significant to non-fatal related an ten ventricle five women make association had diagnosed of additional a possible “In these 17 occurred in or an abnormal I made of 12 August, —— of individuals EEG only a limited 1997 4:1OPM page cases, with on follow-up. evaluation PDT; these As of these 29 the either a I am not cases.11 RE:Docket No.95N-0304 l~In summaryr exposure to possible these are These greater effects “TO test mg. per panel, do reviewed the less the of the the were possibly related inhibitor, and had the These recommended dose associated of with there to the was product. 55 year products the events, ephedra had old I product account these two below working but 42 serious only events one a positive female for adverse I mentioned also in products.” products, only are products. adverse Of were who a reviewed, pressure, products events. are symptoms of the These severe occurring ephedra a stroke other I blood low-dose adverse products, who in ephedra-containing low-dose woman that ephedra-containing 15 mg. per dose. of all with and seizures.~’ events rate toxic associations dose-related, significant events than 7% the Alkaloid infrequent ephedra-containing be that on young of to is a adverse approximately that which have one-third events appear the hypothesis not containing effects of only products dizziness. in the high-dose dose, be increases and side frequency to Ephedrine cases thrombosis adverse by nervousness, side two possible or cerebral non-serious potential of appears infrequent characterized tachycardia, expected These 105 exception there by coronary the Containing of ephedra-containing reactions. “Of Supplements the ephedrine, characterized over with associations adverse 15 ;Dietary who was lupus had a seizure. “ “Based reports, on I have ItNumber ephedra affect day ephedrine fact adverse dosage the with those of the The are to lower 15 mg. vast reactions adverse event the recommendation dietary two main dose of supplement the trade issues that appear the ephedra and of to the the of ephedra ephedra provides majority occurred alkaloid per a margin of with both of to dose, expressed safety based serious products content that and on 60 as the non-serious exceeded these thresholds.” “Improved -——— [1995] and ephedra of the product.” equivalents, that the year’s reactions proposal per of opinions:ll appropriate. assurance “The last group are review following one~ adverse quality medical the working associations mg. my good Version of 12 August, ——. ___ ___ ___ manufacturing 1997 4:10pM practices pDT; and quality page 30 assurance RE:Docket will No.95N-0304 provide ;Dietary dosing consistency consistency dosing recommendation Supplements within product important, is that Containing products that Ephedrine batches. would I can be easily Alkaloids Because add to mis-dosed the not be permitted.” “The ephedra warnings label and labeling cautions and Davidson to my the ephedra From those products brief a very also smokers, history appropriate include those of report and effort to commission industry to pay for on the taking oral cardiovascular cavalier The to consider such or if to of the allocate their conclusion This failure failure is FDA sort the absence of FDA between 3 or 4 minutes and inadequate to any was lengthy evaluation future FDA ought industry to consider the time, energy, is going to of the the reactions causally related / adverse 4 and treat the promised to adequate response caffeine, of 12 August, in the money them in analysis, or and 1997 for for ephedra 4:1OPM Dr. on the such Committee to (rather plus manner. Davidson’s likely page FDA’s to provide a on which have than ephedra caffeine, 31 In report been merely causality) ephedrine, PDT; the Committee assigning herb reaching it has not provided to the as (but, and capricious. a timely ephedrine reason curves in full Reports before to the Committee presented the considering future, distinguished ephedra that) arbitrary a report FDA study Event FDA has promised time to only to egregious Although consider of Adverse minutes provide were without plus or to the conclusion and analysis adverse ephedrine and you.” relevant The FDA analysis indefinite is by default associated very Committee particularly matter. at some this 3 renders to produce subject the Thank only a totally to expend members be manner. failure instead, that I would relationship events. this was the discouraging going of Dr. Davidson’s details to an analysis. analyses conclusion, Committee it appears certainly is not such 66) : “In respect discussion of the Version by pg. with the transcript, The dose I would and the adverse report. report recommended Advisory rationale for questions same use with I with allowed this the (Vol. discuss officials that also disorders.” Dr. happy group instructions. against contraceptives, seizure working , the herb, and the RE:Docket time No.95N-0304 course FDA ;Dietary Supplements for the development merely brushed Dr. reactions. Davidson’s report any specific criticisms providing an alternative report the report before FDA’s arbitrary and analysis fact) Committee they and that of to either required capricious requires be withdrawn relevant were to report the Rule actual off read, reach their of (which without and or Dr. was reconvened discuss Davidson’s of 12 August, 1997 4:1OPM PDT; page to give 32 his data contrary this to very and debate. .— Version without conclusions. made consideration Alkaloids without methodology, Committee, hear, to and the Committee and essential his treatment the Ephedrine of adverse providing permitting Containing RE:Docket No.95N-0304 ;Dietary FURTHER Food Advisory Supplements LEGAL Ephedrine meeting August AUTHORITY 27-28, 1996 LIMITED Vol. I pg. 12 James Prochnow, an attorney with Patton Boggs: !1...a dietary supplement manufacturer is able to inform consumer the of how function a supplement and structure promoted to prevent, disease. As a supplement clarity is or product a drug one just of of the human a effective for or diagnose, result, plain as defined its ingredients body as long mitigate statement for Alkaloids CONSIDERATIONS Committee FDA LABELING Containing that weight energy by the or a loss, does Federal affects as it is not treat or particular mental not cure that Drug a dietary alertness make Food, each or related and ‘Cosmetic Act .“ FDA weight has no loss. against authority FDA prior restraint. actions that FDA disapproves. clear, the attempt by First keeping II pg. As “Can you identify alkaloids itself? And safety issues? alkaloids risk how do also Amendment attempting ignorant not of refers to these this, to prohibition manipulate uses v. Rhode permit - uses Island and made any such scrutiny. STANDARD OF HARM level in dietary serving and per you you containing Vol . I pg. version per Can of significant First that Dr. Yetley: a safe ephedrine labeling 44 Liquormart does to strict 96 FDA’s is them Amendment is subject the FDA IMPROPER Vol. prohibit is violating peoples’ the to think identify dietary we supplements day as well should questions supplements deal of under which 141 Dr. Yetley: of 12 August, 1997 4:15PM PDT; page 33 as ephedrine with use harm?” for a total margin for of ephedrine there is ~ RE:Docket “We No.95N-0304 would question ask from :Dietary that the Supplements committee a perspective alkaloids in dietary ephedrine alkaloids that you well as serving taking third of se, and day limit.” question use under for a large ~ we’re there that is ~ individual.” conditions of including significant harm, which is a risk there “Assuming question and workinq then ~, did will FDA’s Yetley is quoted immediately Vol. II pg. Here he come that there 13 Mr. by of DSHEA Congress to proven by the ones adulterated be the the vires; improper they delegated adulteration Health the by Federal adding are to FDA of 12 August, subpart that of above added) to this that conditions at a additional instructions. a very by substantial Congress, which or more supplement PDT; noting Proof page the section ~ the FDA. Cosmetic Act was (20) . There, supplement of is or of the four talking. ..” significant 1997 4:15PM and provisions (f) (1) to Congress dietary ~ a dietary if one is the a Act, Drug Food, a new presents safety and Burden only A or Education stated This this: it and Supplements FDA. if risk below: adulterated are look you conclusion safe to Committee ultra explicitly deemed you Can use consideration probably b Prochnow: of Dietary 402 of full same effect a (emphasis ~ ask with harm?” have are there is: frequency the “The we means adverse associated @ you conditions And question and are added) authority Supplement “Section version the discusses on Safety main you are from the that gives departure amended give probably instructions Dietary you ..“ (emphasis questions. These after assuminq we levels of significant that group are a per supplements harm? or a serious that use as of safety.” harm fourth total both dietary of significant of sources, identify significant “The the from margin containing effects safety considerations is: Can you of the definition ~ identify ~ risk of adverse that Alkaloids level both botanical about about to ask the a safe for the “.. what alkaloids number least talk you think going ephedrine which suggested when identify in Ephedrine address supplements and per into account you find ephedrine a per first of can ephedrine Containing only will tests “The 34 are three unsafe unreasonable be or risk RE:Docket under No.95N-0304 conditions Secretary of an it’s public ...the lot a the full One related declares FDA, And, be to the committee. litigation which of important “We FDA, other of at that I pg. causes for things. of law and should Committee to predicated version this or lawsuits] is are only is there, when disclosed, were ingested Guilt by and association be not enough look I’m at just specifically ~ for this is sicmificant curious its definition to be a scientific will Yetley Dr. false harm Since use. on the Yetley’s Committee’s redone mandated two within how you subparts, the law.” ab initio whatever deal with neither standard the issue. assume that recommendations come it in the context.” answers that legal the the conclusions false of statement FDA the of must by charged a Committee statute, out of questions nor ordered the Committee were Congress’s recommendations by Congress’s We be harm set aside with the not a different and harm standard by FDA. Vol . II pg. to the to from the statutory to implement that the “I have us sub-definitions, committee, corrects preferred One it people supplements definition, wanted as it goes standard the 145 Dr. Yetley: really work to added) an advisory the two different standard, Formula dietary in a court has Note hazard “ (emphasis Vol. if the it is poisonous because facts records purported which ~ imminent [in the Vol . I pg. 145 Mr. Israelson: II... the standard you are asking arrived Alkaloids ingredient--since whether thirdly, of medical and is not enough harm, that an Ephedrine Secondly, in the label. alkaloid--to or safety. crucible Formula the Containing .“ revealing where Supplements suggested not ephedrine deleterious II of use HHS, health ;Dietary 220 Dr. Fong: a serious committee], problem with the last phrase ‘of significant of 12 August, 1997 4:15PM harm,’ PDT; [in question ‘serious page 35 adverse 3 put effect RE:Docket in at No.95N-0304 least but now, as other milk “With —. loss the because for. ~ a mar~in what is Alkaloids 28 years drinking effect old milk--so to my daughter, @ with, well, quite ~ risk\benefit a clear frankly, ~ when w are what m ~ safety heard use I’m of safety, — I’ve Purposes there’s safety, difficulty serious of a mar~in —- and ~ great who daughter, Ephedrine milk as well or Orientals.” m indication leaves My Containing 222 Dr. Ricaurte: issue purported had presented Chinese II pg. Supplements individual.’ as a child is a food; Vol. one ;Dietary the ~ @ heck are u @ that, don’t @ have @ ~ ~ then infinity because Q some that all @ the a have table qoinq ~ perceived have somewhat afternoon taken answer @ really this beinq left a Q@ use h this mar~in ~ a can’t benefit.” @ (emphasis added ) The that FDA has made the committee for those energy weight then of course Vol. II pg. “Question sure small for which When you risks will by concerning the efficacy it is being cannot requiring widely consider any sold: benefit, seem unacceptable. 222 Dr. Ricaurte: 3 adverse that [the effect there’s possibility ‘of in one many it’s entirely at least significant is, no, I can’t, a fair question with regard harm’ individual’]--I’m that compounds so the answer requirement, per even inevitable any evidence purposes loss. number ‘serious conclusion disregard of ephedra and this can but not satisfy I’m not that sure to the ephedra and that alkaloid se.’! Vol. II pg. 224 Dr. Kessler: “Can I just help Significant supply has those is from protein. People foods production, of 12 August, off the track death--I on milk, don’t think please? the food of products.” incorrect. thousand get seizures, kinds eating Nine to improper version don’t risk--MIs, This shock so we with people can certain a year transport, 1997 and 4:15PM do allergens die from storage PDT; die anaphylactic such as peanut food poisoning and/or page of 36 preparation due of RE:Docket No.95N-0304 People food . especially and, ;Dietary have one MIs rich thus , the Supplements as in fat likelihood a result (which of a heart which disease, our today population infectious sources is a fair number HARM FROM FROM ABUSE USE use. of not looking Vol. II pg. “The special Food and Vol. working do when not sold II pg. 343, deemed label version add as or met with a the percent of disease know from if that RATHER THAN HARM CRITERIA and Unman: of misuse that such the rather statistics, reported than correct ... the enormity products as be of a far greater aspirin, concern.” [should labeling contains of 12 August, in 1995 and Committee determined of injury do concluded or dosage not of the that at withstand that ma unreasonable huang risk limitations, of accurate warnings.” Shapiro: among other branded Advisory group conservative following: Food significant and adequate , 30 I don’t possibility reports working present 52 Mr. [DSI-IEA] to of the anecdotal special information Ilt_JThe Act group Administration The to disease, Shapiro: of these scrutiny. 20 INSTRUCTIONS room should meal, aggregation food-borne MANDATED of Alkaloids of compounds.” of Bass misuse ibuprofen 51 Mr. many label of that kinds of the heavy infectious population, LABEL at emergency and Drug sight a platelet for for may be the result reports products WITH Shapiro lose know, risk for these IN ACCORD acetaminophen harm to say 50 Stephen Also, least at for high-risk injuries the is IS THE CONGRESSIONALLY Vol . II pg. II...we must consumer food-borne eating Ephedrine attack). you area, of increases Vol. II pg. 238 Mr. Guzewich: II...if the CDC has a figure, is my Containing things~ “A dietary be amended supplement “misbranded”] directions 1997 4:15PM PDT; 21 U.S.C. or solely conditions page 37 shall Section not because of use be its or RE:Docket No.95N-0304 “Clearly warnings.” dietary supplements warning statements MOST Vol. ;Dietary PROBLEMS I pg. it was could would contemplated have and product. so BY PRODUCTS Coody, But most Q percentage also. probablv ~ ~ the half between also products appropriately say pharmacist indeed those with herb extract, Vol. I pg. IIsome were recall is the Formula actually, version we source, in those isolated, product = druq z don’t contained have caffeine that were dietary and which were purified all of 1997 it was 4:15PM are, are to herbal pure look which that were again, that ones would at are render extracts.11 of able supplements, the to products determine meaning herb or alkaloids.” them. ‘rObviously the papers, of 12 August, and distinction able analysis Department llIt claimed One.” the not indeed events (Texas those ingredient an actual in fact, that we’re ephedrine the and determine are adverse breakdown?” and that cases contain in mind and and these analyzed~ that keep purified and others 136 Dr. Culmo in percent drug ephedrine Products extracts Vol . I pg. 136 Dr. Dentali: II. ..I’m wondering if you did of them, w supplement the reactions misbranded which that ILLEGAL the svnthetic products are dietary whatever a single, associated and in l’our divisional included are it’s important that a the adverse some added) it’s ephedrine, Alkaloids that effects ARE ALREADY food SUPP lement Vol. I pg. 104 Dr. Dentali: II. . .as we’re talking about alkaloids, side THAT senior about z would (emphasis Ephedrine [by Congress] potential of the Texas Department of Health: !!. ..over the more than 1,000 cases also, Containing be appropriate.!! CAUSED 82 Mr. Gary Supplements to of Health): And first be ma admitted PDT; page I don’t -- one we can do think YOU of huang extract, and that synthetic was 38 RE:Docket No.95N-0304 ;Dietary Supplements Containing Ephedrine Alkaloids added.” Vol. I P9 137 Dr. Dentali: “Quite possibly this is not a dietary ● supplement.” Vol. I P9 “ 137 Dr. Culmo: ItBut it~s labeled as such. “ FDA already contain synthetic market; these engage in ephedra this doses Vol. 1~1 think doing, same producers point, is the the-counter traditional that to have cheaper than and to have no or attempt to to propound that the deal with exceed its unscientific, will harm both the customers. the the and and give out or be a very why they high the that is sulfate task and be do the at culled is mislabeled to to there impossible to ought wants hydrochloride and that’s that really really ought it industry FDA anything virtually FDA adulterated the probably that as for--a the this from the misbranded, would priority. like to ..” 288 Dr. Chassy: evidence these is ephedrine hurts if in only to say and thing industry done. .. I would II pg. “What likely it chooses regulations that agree--by it only Vol. the . . ●nd with It see that no from parties far labeling, made authority specific be .tested I market. one I think adulterated to is that 286 Dr. Chassy: thing. ought ephedrine instead and their The most has products ephedra parties false problem; as misbranded. the FDA capricious there’s and also delegated product II pg. clearly The to remove masquerading and other warnings. and authority (synthetic fraud/misbranding honest gun, are extract) arbitrary, and are fraud congressionally legal ephedrine high inadequate the products such excessively real has indicates a few were cases. .. effects preparation, medicine is that Those which we supplement --neither version of 12 August, 1997 few we might could preparation, dietary there but understand 4:15PM PDT; is clearly cases understand probably we were sufficient in an understand cannot understand nor accept.lt page a smoking 39 overin a in a RE:Docket No.95N-0304 ;Dietary Supplements Vol. II pg. 289 Dr. Chassy: !!...1 think there’s a problem problem is products are millions do a of people on power OTC AND study would FDA Dr. Love: ‘tTexas and Ohio’s data ~ identifv q label, ~ find So ..“ it reactions is not phenylpropanolamine herb) removed OTC is just as relevant reaction information respects, this Committee is noisy; version OTC better amounts of 12 August, be take I mean, that effect can of there in order taking enormous to to these get the do that for to the are per products. afterwards ~ druq, compare This ~ DATA AND ~ database OTC it’s taken rate of dru~, ~ @ Committee’s the ephedra that ingredients to reports PDT; the FDA charge FDA safe and 40 that adverse . In some from because warnings for wilfully database concealed dosage page has as is the supplements the and active from their instructions, 4:15PM adverse pseudoephedrine, as compared information dose, the principal determining 1997 EFFECT HERB supplements. information for drug it’s the OTCS reaction on ADVERSE PSEUDOEPHEDRINE, ephedrine, dietary to the OF added.) possible containing adverse means the ephedrine people IN EPHEDRA OTC that containing herb less out (which ephedra many Alkaloids and effects. ..You cannot ~ product (Emphasis reported in ephedra to FOUND includes Where database. the EPHEDRINE, 226 FDA’s ~ of and any damage. That have CONTAINING Vol . I pg. @ that doing trial ephedra CONCEALMENT ALKALOIDS ~ clinical Ephedrine expensive.” CAPRICIOUS PRODUCTS not. clear them. PHENYLPROPANOLAMINE, does of to see the adverse it is incredibly ARBITRARY safety without taking it the very clinical people, statistical study; it~s repeatedly meaningful products ON comparative means --and alkaloids these the with Containing it are the is all RE:Docket No.95N-0304 specified in FDA important data OTC on reaction reports. infamous bias tightly ;Dietary monographs. many ephedra One concludes against regulated a new Committee dietary drugs. that Supplements FDA that FDA SUPPLEMENT USERS AND THAT NO FDA ACCEPTS a interview of the manufactures million must Herbal units be of Vol. CEO Ecstasy this absolutely extrapolation market the said product. enormous. from this of supply in OF “PrimeTime Live” there Angeles sold EPHEDRA television alone in to that sold this further information convene company firm any more information. FIGURES amount its of and NUMBER his this adverse favor INDUSTRY Los Alkaloids exhibiting its Rule ON that The Is type is and DATA of which FDA withdraw Vol. I pg. 240 Dr. Ziment: II.. .I’ve got a report here in not to all relevant PROVIDED Ephedrine supplement supplements has access THAT did dietary FDA must ADMISSION Containing 15 country details guess or what the is?” I pg. “I think defer 240 FDA’s generally Dr. Love: FDA do not have this data and will have to to industry.” FDA’S Vol. I pg. “The most VIEW OF TRADITIONAL USES OF EPHEDRA 75 Dr. Culmo: common respiratory prescribed NARROW traditional disorders. or enhancement, There promoted for stimulation, use for ma huang is no evidence weight loss, or euphoria, to show is that athletic as to is commonly (over 2,000 treat it was performance practiced today.!! This prohibits version is incorrect. horse riders of 12 August, A who 1997 Chinese are 4:15PM law under PDT; the page years old) stimulating/euphoric 41 RE:Docket No.95N-0304 ;Dietary Supplements influence of ephedra herb from galloping villages. that This the ephedra Chinese “What changes science filtered science at all. FDA 8, 9, serving more later, of. SCIENCE change.” since the Committee/s the scientific doing 1995 meeting data. This which is is not 10-fold a that in daily and requires 7 days. Committee of which ranged limit gone I’m quite not here from an sure on intake meeting O mg. supplement or of of 24 alkaloid is adulterated alkaloids recommends conditions mg. or more or more not to use transcript ~ records consensus containing of 1997 4:15PM is virtually PDT; page in of a AND dietary the 42 per of 6-hour the product the if ephedrine 1996 for a limit to 60 mg. of the alkaloids FDA now proposes FACA, of ephedrine 8 mg. warning showed APA, DOCTRINE suggests intake The of 12 August, already VIOLATES a dietary a label ephedrine from ’95 until and (reg.) or more labeling result total October that.” 8 milligrams if its from we’ve AUTHORITY dose version months down just OF CONGRESSIONAL daily The THAN considerations, STANDARDS than Advisory political that level OF would alkaloids misused) are aware fact that in the CANADIAN or or don’t to the telling FDA proposes that period 10 we’re it contains use it’s ADOPTION The facts drastically changes through safety DELEGATION law shows 221 Dr. Ricaurte: ‘?1 think basis The changed significant II pg. what MORE Alkaloids through sometimes FDA and Dr. Culmo is referring have any estimated steeds influence) (and BY POLITICS is compromise. without are than their the used Ephedrine 68 Dr. McCausland: recommendations we under traditionally AFFECTED Dr. McCausland Vol. (driving purposes MEETING II pg. DUI have for more COMMITTEE Vol. early tea Containing for Food on the supplements, a day. same limitation RE:Docket on the No.95N-0304 dose dietary and ;Dietary length as supplements decongestants single than repeated ephedrine has to 6 to four Ephedrine containing recently ephedrine: three Chief Ho, Bureau of Pharmaceutical at the Food that Her of Containing done 8 mg. times ephedra for of Alkaloids OTC nasal ephedrine daily, used per for no 7 days. Dr. Micheline data use Canada containing dose longer of Supplements Advisory led the Canadian FDA It rulemaking. of also Vol. meeting, may the influenced I pp. to 106-122, decide limitation some Division, of the appeared none on influenced have dosage Regulation but provided government however, by Product Assessment, Committee presentation, determination of the of the that dose. the final proposed in Committee the members. For example: Dr. ephedrine the Vol. Wang, II is allowed sustained pg. release product, the but again I am just pulling that Israelson, we’re adequate it’s Canadian being used 8 milligrams Dr. of total Canadian experience would anywhere be ephedra and respect Canadian 24 to levels, 32 materials that’s Vol. which and with something good that support and comply version of 12 August, the with.” 1997 model to That would proposal give a daily concur as And my on 6 to value of added) in dietary one without be based level to food, added) follow. it would on reservation Canadian the safe 3.1 milligrams can make the in terms with the supplements per day of calculations of per-serving the after and per- added) 191, pg. “...if 6 to 8 milligrams without milligrams, the for cases would II were crucial “...1 zero then that day factor, (emphasis with drugs per day 198, (emphasis Israelson, Mr. is that II pg. to ephedrine day recommendations.” on that (emphasis in that alkaloids, with based alkaloids. between “So, OTC safety per as a figure.” 223, proposal Vol. 10-fold 15 milligrams a reasonable alkaloids.” Fukagawa, a repeat is there of that 28 to 32 total maybe II pg. I would the 150 milligrams that decisions evidence, understanding that Vol. making is way, in “...since what, to consume, following Mr. 189, the addition manufacturing industry 4:15PM of be able page 43 added) PDT; look 4 times practices, would (emphasis we other I and at daily, the or stimulant think willing that to RE:Docket No.95N-0304 Mr. have Israelson, a lot Canadian your dose of labeling data and length Committee presented of and length the dosage standard or safe Under controversial the debate evidence used accepts the examination (Federal Moreover, authority to of supplements VerSiOn of 12 August, Food Advisory that Food Advisory to Committee support was no the because Israelson, was those on the on (relatively) certain limitations. the data dose Canadian Act) , the examining comment the representing Procedures these meetings consensus yet it were Canadian Committee limitations, putting the ultimate Canadian data into data, used the the regulation the procedure of ensures important to public basis another open conclusion for the 1997 have to scientific If the FDA further bypassed determination American the public are a for that is examining violation of FACA FDA the Act). has determinations It access rulemaking. determination Congress . remain without the FDA will the and process. government’s to may public issues decisionmaking analysis, Committee dietary the the data government’s meetings make determine The of notice-and-comment the solve established. and critical Advisory to and comment. without in the agency’s underlying to at the FDA to accept identification adoption helpful the available Mr. public APA , purposes what to data use adopted Canadian without data of but at least and able these There standard, the Alkaloids nor were (Administrative was be presented perhaps and permitting would we~re follow government evidence because be this essentially that not 1996 urged APA how the standard the and limits. and Ephedrine ‘lUnder DSHEA, Canadian were duration cannot establish if the chosen, the say, weak interests, standard made 1995 of use was Per would examination or very politically that Containing added) use public no 193, of 1995 or 1996, at the provided The by meetings for American industry would used Supplements II pg. (emphasis The salutary Vol. labeling concern.tt record, ;Dietary did 4:15PM delegated on not safety and PDT; to issues cannot page the 44 concerning delegate this RE:Docket No.95N-0304 authority to the constitutional Canadian by llth considered and findings not part law the propriety of concerning vacated a limits for 428 Conference of body’s findings making detailed statutory version court government IIdid not of 12 August, (See with adequate v. 962, 4:15PM 984 PDT; standard part the OSHA the the court exposure agency may OSHA, to U.S. as “rely by the (llth Cir. 45 the (such American , the outside responsibility Occupational air on organizations for explanations, page court of subject Hygienists) of other the case, established AFL-CIO 965 F.2d 1997 while OSHA any permissible of outside relieve authority which not by the of the standards that set Industrial findings, Administration. to that values’ Governmental In identified found in and Alkaloids of a 1992 decision (e.g. , not rulemaking limit criteria. Appeals etc.) . have of the Canadian incorporation and documentation” ‘threshold the Health OSHA substances The recommendations States or was part organizations meetings, “generic” contaminants. as open of of OSHA’S outside of the United Court not rulemaking Canadian issue Ephedrine FDA does the the use same Circuit U.S. The the Hence, This Containing redelegate to entity. is unconstitutional. the to Congress extragovernmental by Supplements government. authority them given ;Dietary Safety 1992) for all and RE:Docket No.95N-0304 ;Dietary LABELING OF EPHEDRA FDA’s CIIN]O one created a United States, [several to Supreme The Court. of the The First prohibits the misleading District (Civil Bill rules before somebody of in order example, trials information Version no outlined further the in by the the U.S. limits Constitution Pearson FDA to absolutely that & Shaw, is of D.C. proceeds with its before at this Court neither et. al, have Commissioner District the U.S. very for the proposed Food Drug a the moment. District Rule, it is of meaning then consider the There the Administration defend, we are to suppose obligations, them. and to “protect, devoid Court not permit has and uphold” that the oath and that the FDA Commissioner is of can be no excuse of taking constitutionality the 12 August, on as a effects 4:30PM PDT; clear choices. published weight it to keep public the adverse 1997 made government to manipulate ephedrine on quoting under interpreted v. his that it is the First responsibility. information of are (EGS), Unless Supreme does 7) granted labeling the of office, it proposes Us. Amendment public FDA seriously else’s The against a ritual incurs to at York lawsuit. Constitution. obligated US Indeed, 95-1865 the U.S. oath the for the District in his oath of the powers describes banning promises, is simply (New government. from Commissioner office Constitution op., Rights FDA If the (slip and of No. [t]he powers~l) powers) Amendment for another The The of federal Court of Columbia) asking government lawsuit Action limited federal nor deceptive. Amendment that (1992) the Alkaloids Is Limited —f_ deleted]. (the enumerated the powers U.S. of Ephedrine SUPPLEMENTS proposition U.S. citations Constitution the Containing DIETARY Power Government 505 Constitution First Labeling disputes Federal Supplements loss peer information That page It for clinical also received 46 from the includes, reviewed aid. reports that by includes the FDA RE:Docket from No.95N-0304 consumers as in ;Dietary using OTC (which of ephedrine If there are decisionmaking, the embarrassment or trumps the Quotes from Rhode Island use cannot Supreme ~sIt is precisely suppressing freely available, (quoting from Relations, 413 U.S. llIn case after Court, and individual stress the importance consumer choices or accurate ~commercial~ they the Constitution 44 Liquormart it.1~ dangers First an v. Members of ... public the information. Court, through 77o have of us,~t on Human (1973) Pharmacy impropriety opinion for Comm~n 37 L.Ede2d. of if it is makes Virginia the will unwisely of its misuse Co. v. Pittsburgh following public (at 8) between the dangers Amendment 2553, the inforxnation of choice, 93 S.Ct. of what be deemed that commercial the case know FDA~S may in assumption Press 376, the (U.S.)) and the Pittsburgh to agency, decision to suppress that right information Court this kind information, a in or inconvenience. paternalistic a decision involved the embarrassment nonmisleading justify has to (1996 WL 241709 truthful, alkaloids and the principal norephedrine, of this inconvenient u ...a State~s same Alkaloids pseudoephedrine, factors public disclosure U.S. the Ephedrine in humans.) the agency’s the containing is racemic political then Though Containing ephedrine, phenylpropanolamine are. products ephedra: metabolize Supplements Bd., the continued to manipulating the suppression of ..l~ (J. Thomas, concurring, at 21) QUOTES FROM COMMITTEE TRANSCRIPTS AND COMMENTS Food Advisory August Committee 27-28, Meeting 1996 Vol . II pg. 12 James Prochnow, an attorney with Patton Boggs II.. .a dietary supplement manufacturer is able to inform each consumer of how a supplement or one of its ingredients affects the function promoted Version to and structure prevent, 12 August, 1997 of the human diagnose, 4:30PM PDT; body mitigate page as long or 47 treat as it is not or cure a RE:Docket No.95N-0304 disease. As supplement clarity a is or product ;Dietary result, a effective for a drug just Supplements statement for as defined that weight plain a loss, energy by the Containing does particular mental not Federal Ephedrine dietary alertness make Foodr Alkaloids or that related and Cosmetic Drug Act .“ Vol. II pg. 262 Dr. Ricaurte II...I~m surprised at the fact that why these taken compounds, products, members no that uses be surprise. no use risk/benefit FDA benefits may use, eliminated. customer. been benefits: well that is able uses distributed the satisfaction have and been and Committee considerations. studies times times day during officially of oxygen (page the meeting. uptake “Other actions yet another and is withdraw and thermogenesis example arbitrary, forbidding and develop I pg. Version Rule of any benefits the of ephedrine of (heat notice.) from ephedra FDA’s bias capricious, and proposed Rule, the members re-convene from the considering to 153 Dr. Ziment 1997 4:30PM PDT; page 48 their three FDA even stimulation production) .ll on the supplements is supplements, fact. FDA Committee, all give several prohibition a new rule. 12 August, to include nutrient contrary loss, not of this. dietary against the ephedrine or energy FDA’s where published referred ignorant the from reviewed were is to does of 20 mg. al) uses weight a supplement peer of the promised appetite, of FDA is not 15 of the proposed consideration et of ones DSHEA the mention disservice are further, controlled Astrup, any are receiving and effectiveness (e.g., admits uses of benefits placebo gross they Note to exclude of the safety per mention reduction energy. to FDA blind label a Committee in evaluating that common whether the requires being most or authority Double instructed be considered which as to judge alertness has Prohibiting as Note consumer mental The of ephedra unconstitutional Vol. have of potential off the table...!! It’s from a number relevant must refrain facts, RE:Docket II No.95N-0304 ...the patients standard drug individual magic, is ;Dietary who are Supplements taking produced by looking for magic. going to they’re not recommendations. So an herbal even if in the drug, a person effect simply going to that III think effect.” scientific control and that’s not going And II pg. “And the of things that the think The FDA looking of exercise for ephedra a particular drug people that scientific of for the the looking amount expecting to give some them sort free of behavior, either. going loss to know this of cannot (FDA) of the bag. We can and all of that this remove the other is something work.” required the out weight still efficacy When FDA are will they government firm, by really is already regarding has for public. the labels and people but the than to be easy.” frankly, they else, down Alkaloids 245 Dr. Benedict Cat, evidence limit way its not constitutional, Vol. all the rather somebody’s bound enough we’re over if who’s take Ephedrine pharmaceutical And we alkaloids is medicines ethical be Containing prevent in loss that has is trying of to ephedra public as a source committee weight information information to keep from information disregard from which them, plummets and anything reaching they their until any the think the respect for it is all but ignored. “In the May of consumers trust nutritional shift list as value 5% has and government of ago for Marketing Institute, Attitudes and How to Version the from pg. Make food at groups the 1995. Trends Supermarket Products 1997 dead of 4:30PM PDT; 45% for assuring the from government last at foods.!’ (data United Washington, Really page year 13%, food A which look in the last 3%. as many Stiedemann, Consumers survey, 6% government, twice 1995, and up 23%, nutritious 69 of Sloan 12 August, fell Today, assuring eat, at expense [1990]. Institute] on themselves they followed consumer the [Food Marketing no one and rely occurred five years quoted FMI Manufacturers [1994] . stores 1995 led from 49 Food Consumer p. !!Guaranteed Wantll the to industry States DC, major in 57, as Success: ~ a RE:Docket No.95N-0304 , Functional Nutraceuticals, No. 1, 1997.) The ;Dietary (emphasis authors Supplements k Medical report the in conducted proprietary motivates consumers to purchase found 72) (pg. Foods that disease; 54% for increased increase alertness; (Haworth 27% same research products 62% in just It is suffered it for a decline of by labels) or by limits decline As proposed Rule cause loss mandated use will area of nutritional prevent 31% to treat medical authors note, has come credibility in bogus ones. All a supplement uses of any harm is in problems relevance because will just FDA to the addition by FDA’s it not posed will The warnings, on bogus credibility information. label its as mandating be upon continues prohibiting to has relies dietary public this constitutional FDA (such consumer all government the public as cease great of products like of a complete lack makes the product “In fact, . ..all have been done things this this ephedra to FDA’s the Rule. in spite that (such it Vol . II pg. 37 Adam Gissen II. ..one of the most telling the to the the disinformation cause stores. fitness; the consumer information of insurmountable proposed mold until will what food supplements If government’s the in 1 have determine 25% that use) , the further whatever to providing for Vol. they supplements to which information. limiting to stress; above, extent attempting choices Alkaloids years.” the in the nutritional practice time from that 40% to improve reduce a few short clear, Press) in health purchase energy; to article and 21% to fight depression. problems; II...the diet and disease connection with long way Ephedrine added) recently They Containing of to has some been duration of scientific safer the over the or more studies to of time. information limit This is indicating effective.” that a duration desire have been significantly done on longer than supplements for one week.” Millions periods requiring Version of people of time the far label 12 August, have used in excess to state 1997 4:30PM ephedra of one week. a one week PDT ; dietary limit page FDA’s proposed on duration 50 Rule of use RE:Docket No.95N-0304 will backfire in the customers credibility (e.g., of increase I pg. The working should be below This in label pg. and more not for are all shown above the serious an idiots. and a use or .’! confidence consumers increases that risk of that it does believe that dietary untrue; market This is supplement population Rule customers in formal mandates label consequences will inevitably withdrawn, new Committee is modified label statement FDA’s adverse Rule advise dietary The and effectiveness consumer to general limit frequent instructed seems the proposed to bogus that drugs, more reduce ought FDA alkaloid increase will not the obviously and scrupulously honest Rule re-issued. above certainly Warning -- in temporary who is not kill physiology Dr. Jones sufficient, the exceeding herbal one extra street drug the maximum roles of permitted line on the look-alike intake may impotence.” understand cautionary the will appreciate the catecholamines the scientific rationale in for statement.” is entirely it is truthful, correct. His statement not misleading, useful, effective. Version and responsible OTC that than intelligence. if the will warning; warnings 280 Dr. Jones “Finally, very or using held, subsequently this false repeatedly and meetings mammalian of the arrhythmias ephedrine marketed does effectiveness. unless “Those 99% reduce justified directly the Instructions use disinformation, result will cardiac consumers instructed consumers education that advise considerably market: that Alkaloids and deaths. for currently warnings. have 1 as Ephedrine A warning misleading the FDA “agreed is patently supplement average or such reactions reactions, surveys manner. pharmacologically making that than increase label real should frequent adverse Vol. the group more occur false Containing 42 Dr. Larsen instructions not is thereby Supplements serious know in adverse Vol. more a very contraindications hypertension) using ;Dietary 12 August, 1997 4:30PM PDT; page 51 is not a bogus and likely to be RE:Docket No.95N-0304 The FDA assuring have does that on adverse Vol. a Supplements supplements warnings. sold No warnings 31 Ms. 1995 warning states, dietary role interstate commerce products warnings in were associated statements of warn,ing as “consult statements, which the product if consumers experiences certain medications, collected any bore such your to product ~ suffers with Apparently certainly the rather FDA mandated than the the product drug fi label usage 1993” cause-and-effect established. ..l’ 12 August, (emphasis 1997 warning not to use conditions, taking due to havinq certain a toxic level u-mm added) on the label. for FDA action and This is -- so long not which misleading, will reduce official) or the consumers fact ~ serious as in most have adverse cases of are added) PDT; page that as statements may relationship 4:30PM any to the consumer. because reporting specific any of the warning “Although general beginning is truthful to misuse directions, bear dietary very medical disinformation did not contain and ~ area are warnings due man warnings (Canadian perhaps labeling, recommended warnings 121 Ms. Ho “Subsequently, young and useful proposed of all I pg. no the recommendations (emphasis were a legitimate credibility reported there not of age. it, of course, ..“ more effects, a certain of before to percent did from from various adverse dan~erous. percent physician include 15 review ranging program” tended taking 85 kind; Vol. I pg. 91 Frank Wickham II...we’ve had this death of this of ephedrine, in the statements exercise or is under Approximately meeting): supplements or Version legitimate inadequate of number group nutritional in or Alkaloids Binzer working supplements Vol. in Ephedrine reactions: all the as Containing constitutionally a disproportionate I pg. (From have dietary adequate found ;Dietary 52 a food present exceeded reactions adverse not were event firmly RE:Docket No.95N-0304 On the Canada now basis ;Dietary of misuse disallows the ingredient in traditional no permitted longer labels. Canada Supplement Committee hence “YOU seem to have versus asked I pg. “I don’t teenager who label tablets you want that the abused today ephedra alkaloids Version the to usual Act) and you proposed of the is is a plead 1997 day The ten to be one was a told instead effective rule a maximum happen in of or if the destroy dose time U.S. the of of The one of week mg. limit, the FDA’s ill warning and increase the incidence has already of adverse happened of the consequences. 53 20 mg. and supplement page 8 integrity dietary PDT; male, added) without ignorance that being tablets day 4:30PM other Canadian for it us which in a middle-aged per theory; with I know Ilpeople were the to share cases. standard ephedra not two (emphasis about ephedrine determination, industry and thereby and FDA cannot 12 August, will the do take per times Rule labels This times the you condition. to association representative) the product dosage committee relationship?rl effects yes, informal what the government about of that Could product.” want and issue a causal faster.11 three exactly the reached heart drug if you of Canada Advisory Procedure causality was and, instead reactions. of there directions three instruction (Federal this consequences. the alkaloids credibility (Dietary cases, itself a predisposing ephedra designed DSHEA serious to cardiovascular limits is FACA is warning if I heard of details FDA above food in Canada, (Canadian to lose weight If as policy and how you a lot related with of two serious 133 Ms. Ho I think, ignore its use for FDA action. national evidence did, have one was a warnings, appropriate (Administrative address cases you obviously two to cause serious Vol. set scientific alkaloids those and Constitution, Act), Alkaloids as a non-medicinal mandating a U.S. as a model on the basis being than APA important of ephedra remedies Education an of Ephedrine 133 Dr. Chassy correctly, is and can not be used I pg. herbal Containing a lack inclusion not have Act) , nor Vol. and/or rather does Health Supplements in RE:Docket No.95N-0304 I pg. Vol. ‘lWe have ;Dietary 157 Dr. David two very associated with under discussion. We aoinq @ not do reduce G something safeguard that with the labels did the Vol. Were review duplicates (not in the ~’Product labels, was an where any the could to be present statement was products; drug noted were on something to specifically products, Version was the the hazards added) about doses on the to FDA’s identified 125 ephedrine listed terms same what about labels different formulation) or raw as ma such values or that herb.” huang or market dietary some of specify as an extract found second alkaloids, alkaloids, for the range being products the form of is, whether it llIn some cases ephedra without or a concentrate, on the products of ephedrine were higher alkaloids known herb.’! warning statements on 14; disease maximum effect word ‘Do were daily not ‘exceed. ‘ and age restrictions 4:30PM was PDT; at or condition 25 products; 1997 because warnings (referring statements 12 August, convinced and concentrate, the But I am can’t say interaction has You actually of ephedrine the predict. about did not necessarily in the natural noted somebody here inadequate market no never he did not state review) Vol. I pg. 174 Hardy II...26 products had them (emphasis Hardy analytical have needlessly to first be expected world. You~re to at compounds However, which clarifying going have the risks. can’t died the ingredient the ephedrine you necessarily a those this containing source Alkaloids the products? however, extract, further than no or 1966, products the botanical in products misuse supplement Ephedrine examiners products, never that is correct. April collected You’re products.” 169 Constance in reduce stupid there medical the communicated individuals I pg. the of individuals on these warnings. to zero. these Dr. Kessler use need wasn’t associated that everything two information the very against those cases @ Containing Kessler real least Supplements all; states a were on 37; adverse use general on 86 effects imperative--that~s exceed’--you That was page 54 35.!1 know, on 35 of it the RE:Docket No.95N-0304 Vol . I pg. Death a 20 year of an ephedra-containing although exceed the old label four (pg. 206) the in a 24 that the hour cause synergistic Dosage label. a is with as false a 275 Jones 300,000 users and has failed occasional with failure failing to comfortable herb to reveal follow under GMP with a both incoming to raw and tolerance, one real very very nervous Version 12 August, adverse to this with the an ephedra (e.g., Herbal should and be did not products the system, and We have words, up kept who to awake a at followed are manufactured and finished when had associated other in those concerned the of products building being over we analyzed product looking for at their system.” things to that to the especially 4:30PM in specification, alternative rapidly -- and occur range generally and late covers effects. were intake a strict of 1997 accord can a particular it too nervous poor central due however, surveillance tolerance on the central Love; promotes Vol . II pg. 37 Adam Gissen II...these products have negative a to stated arrhythmia that pattern.” ephedra not report in and alkaloid that’s and use instructions materials alkaloids “And four look-alike these low ‘l..the conditions drug but complaints instructions.” labeling label with label effects eight pseudoephedrine, by Dr. market complaints, these took alternative” coroner’s not any serious level. .taking night --and ephedrine Alkaloids commerce. of ephedra start given misleading our to take “cardiac was abuse, States, minor The street and Vol. United to who drug ephedrine, not FDA that in interstate the were of drug prohibited I pg. student “street of death was of supplement Ecstasy) “In Ephedrine and caffeine.” case We agree dietary Containing college period. effects information clearly male instructions phenylpropanolamine, is Supplements 205 Dr. Love of tablets ;Dietary PDT; makes speed. effects used something People of page 55 develop ephedra responsibly, like on in the other RE:Docket words, No.95N-0304 starting recommended at effects of agreed that reduce the slowly risks should FDA’s labeling more Ephedrine building to universally the be up to Alkaloids some days than withdrawn. a full reduce seven day this, to impossible, dose the and state a and hence Instructions over a period adverse limit would instructions. labeling should will a requiring Committee days with label that to few agree the be the a days makes build-up several cardiovascular of over We of rule the members dose part proposed requirement a slow to reactions. of seven effectively which of reactions will be a far almost ignored. Commenters approximately amount slowly Several increasing use period days Containing rapidly too . of adverse it recommending few and dose very ephedrine, Unfortunately, this low develops that maximum a Supplements level.” Tolerance believe ;Dietary Pearson 1.8 being grams adjusted total of 20 mg. used in & Shaw per on the of ephedra this and or pseudoephedrine, formulations dose of ground basis of lot there it is no contains containing ephedra analyses No alkaloids). product, methylxanthines, license herb to extracts caffeine or Here phenylpropanolamine. contain ephedra synthetic no (the a are other ephedrine, are the label instructions: “DIRECTIONS : Add tablespoon of mix. a couple a cool, dry place. morning USAGE: as soon serving before “CAUTION: KEEP your For EXCEED wake three then to when one heaping tea to stand SERVINGS closed days, From water the mixed For the up. lunch. cold THREE lid tightly first as you or Allow briskly. A DAY! not Keep in in use.!! drink one serving next three days, on, drink for a third in the drink OUT OF REACH OF CHILDREN. especially if taken if 12 August, you 1997 are May for use by children, insomnia too soon before taking 4:30PM cause Not PDT; asthma in bedtime. medications, page 56 a serving dinner.” women. physician Version Keep hot lactating or individuals, of DO NOT before one hour pregnant Stir of minutes. “SUGGESTED second 4 ounces sensitive Consult anorectic RE:Docket No.95N-0304 (appetite suppressing) Do medications. lactating (especially glaucoma (angle or disease, days taking of allergy antacids containing label if you not (monoamine with this discloses this use. that the (primarily ephedrine)”m on the label one of our attorneys (who worked for the FDA should not do basis for declaring the We drug. it because believe our that disclose that amount per dose of ephedra initial final This that dose very of would purposes, the FDA has that of by hence be herb of include a ephedra advised years) by that statement new as unapproved containing products stating the the total over day a period of seven increase day of rendering a well will product For all increase and full these practical labeling their made maximum with all the days. be dose the to a labeled full prohibit slowly from per dose one dose once uncompetitive. as to met the DSHEA’S labeling Committee the basis for in the seven day limit appears 1997 such 4:30PM burden limit members about 12 August, to this rule mandating only doubts Version use dose that over a days. not requirement comments may use alkaloids of daily and customer of several FDA days; ineffective If 20 mg. for many increase day proposed allowed, the instructs per rate seven be instructions period times by the FDA’s drugs. alkaloids. ephedra mg. 14 the but were on the labels, instructions conservative period effect 20. three 20 mg. unfeasible use of might ephedra information these FDA formulation all should Note the within ingredients ‘Icontains we tea thyroid product.” to put alkaloids hypertrophy, Avoid We wanted herb or disease inhibitor powder. ephedra pregnant psychosis, oxidase) discontinue aluminum are prostatic drink Alkaloids cardiovascular cardiovascular diabetes, Do Ephedrine or hyperthyroidism, develop, also tea pressure, disease. MAO symptoms The blood arrhythmia), Wilson’s after this closure), Containing antidepressants, consume high cardiac Supplements drugs, not have or ;Dietary use and of to proof seven consultants a limit. FDA’s to be their use PDT; page for days. also primary A their number expressed interest of it to prohibit 57 RE:Docket No.95N-0304 any labeling than seven Claims which end run day rule receive that would non-misleading benefits First uses 36 of long-term the may Supplements suggest (See pg. promote around scrutiny would days. that ;Dietary which the FDA Ephedrine require Rule thereby notice, Ila. attempts an that their judicial leniency than the to a prior restraint as labeling when used for longer order to keep the on such suggesting periods of time Alkaloids longer believing more speech would Proposed use.!!) Amendment, apply Containing seven strict truthful weight loss (eg. longer than a week) . In possible weight consumer loss safety. to both alkaloids reduces admit this “FDA disclose by a the they say comments pattern of created which cause those and stop taking FDA or the proposes recommended death.” (including DSHEA and by consumers require it may is that true proof that a alkaloids three times dose, most than years. to TID, just Unfortunately, labels 2 permitted 8 mg. on how much 3 times the amount of ephedra taking for years. Version 12 August, the risk of adverse events use.” heed This is 7 day another use limit, it to repeatedly start more a day Those who 4:30PM will per be dose know PDT; that much this for a week will have get any to take. receiving that seizure, of anything FDA page 58 its doing to about has 8 With take for many information Those is than maximum. consumers the less continue been than severity specifying consumers won’t stroke, FDA has not met of Rule it is reasonable dose too death, as consumers alkaloids 1997 label I’Taking more attack, warning consumers label say taking can cause mg. more even should heart that proposed a low They statement labels cause for their such ephedra warning proposed who appropriate ephedra proposed of Notice, the FDA’s to Rule starting the of reactions. 48 of the risk development effects adverse whether increased the cardiovascular on pg. and water) of that of increasing serving While burden aware the regarding supplement. to oxygen ignores of these stopping risk will and on the possibility information-free FDA well CNS iatrogenic the is the risk when requests benefits, FDA tolerance label from who take the same have been drastically RE:Docket No.95N-0304 reduced the more, dose thereby reactions low dose (8 mg. will warnings TID) have such hypertension containing applied how an FDA’s above unwarranted doubt as take “Don’t make Alkaloids take of more ephedra sense much adverse There will be and capricious the arbitrary warnings -- a loss cost of in a have serious cost use increased consumer to or more, been product is, if widely involved it used if FDA inappropriately adverse confidence have proposed a that of all you above applied a justified if FDA’s that such supplements, truly product alkaloids to essentially and if years. by real The of those warning ephedra this size to -- may with arrhythmia.’! much of on of the due Ephedrine risk Rule bogus experience to doses requires much increased be considered previous 20 mg. many severe the or a cardiac would to Containing death. casting warning subject of who thereby death being Supplements not by exactly application consumers for -- but or even The ;Dietary in reactions fully and justified warnings. On page proposes more most the (See pg. 47 Ephedrine the reputable clinical same trials with of the same also the FDA published ephedrine compound with FDA not not be only effective) respect to , the of all States and reduced. of the United aware there of are The Committee is (though not page is well a aware from lie. of of controlled necessarily on in the herb) 59 or alkaloids.1’ transcripts placebo contained data benefits This alkaloid. blind any ephedra Notice.) when is credibility double PDT; this may be more containing ephedra 1997 4:30PM above, the that Rule notice, quantities is not establishes that reviewed 12 August, that the people proposed peer amount Version show Rule (particularly supplements the may be seriously both is the principal meetings commented I’The agency that of “Larger loss) will saying dietary proposed quantities misinforms by of have weight information use statement we on the label Congress page deceptive use, FDA then 100 larger obviously common warnings As (since so other the the effective.” is the of to require misleading it 47 the that RE:Docket show No.95N-0304 that it can (inconsistently) the proposed misleading on of arbitrary, of more of FDA’s On pg. 4 and This the act. it may imply there Moreover, containing drugs cause Rule risks OTC (over and is a not which mg. with for foods of for dietary benefits attendant on to against the section this the supplements, because, Version 12 August, — 1997 that the for ephedrine 4:30PM PDT; risks. is of oral products data apply page 60 not above, supplements bronchodilator that has is and alkaloids. dietary “tentatively” OTC of section as stated are manifest.” argues here. of it per dose) FDA with risks ephedrine The mg. concept (12.5 to 25 mg. here. 25 402(a) including consuming containing under and in concludes a 402(f) (1) (A) of the act, effects, here, in on a weighing While in section 12.5 under not. and use hours) under use data no application product food or has 24 is based of the question alkaloid in favor asthmatics) exceed in drug involve mild to for drugs OTC permitted ephedra is further and ephedrine on doses FDA says: of data, 150 evaluation FTC the supplements of The warnings larger supplements for use, as stated that on reason, Notice, (i.e., harm demonstrated levels COMMENT : of equally severe ephedra dietary exceed appropriate the to these use to some no was containing applicability question to reach are 17-19 OTC drugs. not be used risk” is necessary in of the use will than contained of safety only that benefits, data not may “unreasonable that Alkaloids Indeed, on pg. more (physician-diagnosed benefits The whether labels contraindications approach require drugs that for determination the proven discussed required) the population hours, to against regulated directions warnings The bias concluded restricted Ephedrine loss. advertisement contrary considered tentatively limited An 51 of the proposed agency weight are even supplement alkaloids heavily for attempt capricious, indication every FDA/s dietary same Containing be illegal, no prescription the “The studies Notice. case, ephedra Supplements effective these would counter, be Rule In any ;Dietary the no to OTC drug application a restricted RE:Docket No.95N-0304 population with ;Dietary directions contraindications. anyone events and valuable data for evaluating abuse and alkaloids. of adverse 73, and events were FDA argues The weighing and that a result will benefits they concept of “unreasonable of the act) may risks not and benefits, necessary number of ephedrine But , in the supplements who or not. consumer is quite lost weight has dietary supplements nearly The dietary oral a “demonstratedll all dietary This FDA which then supplements 12 August, states that 1997 67, of is FDA it has of the that with including it is are these loss whether he than approved that loss. getting energy, or she to assume those “health be denied very that few and capricious. ephedrine permitted (12.5 to 25 mg. ephedrine PDT; has a risk/benefit of 4:30PM a claims,” on levels a dietary are or no are weight they weight the 402(f)(l)(A) There using a only indicating whether IIthe risks on supplements, helps arbitrary, 69, against admits alkaloids.~i will 68, based of effects, other the for foods, If the FDA is going benefit to most because. .there evaluating and attendant containing drugs adverse of the products. studies of supplements is unreasonable, bronchodilator VerSiOn of of that in section here that case energy. for The it is consumers the containing 63, drugs for dietary judge may resulting exhibits 62, evaluation effect the capable for ephedrine analysis, In events are 60, not. peer-reviewed or gained nothing analysis. for are benefits 56, question a thermogenic final that (as stated “some that published has or length Adverse of the use of the product is appropriate benefits choose. may not be considered that for any by phenylpropanolamine, or misuse harm and freely reports of abuse risk” to reach demonstrated then cause imply published safety warnings supplements indicates the Alkaloids of the OTC drugs review benefits whether dietary (exhibits that use ephedrine, Our may the adverse products 128). of the proven the risks the taking rulemaking 100, improper reviewed containing proposed 71, of We individuals pseudoephedrine 70, misuse and with and used purchasers abuse ephedra events their and Ephedrine may be purchased population) from the FDA’s dosage Containing use OTC drugs a restricted at any limited resulting provide from for However, (not just of time Supplements page 61 per consuming dose) in are RE:Docket No.95N-0304 manifest. “ Committee meeting experienced A in number both Version .—— these and misuse 12 August, —— Supplements comments consultants practices indicated risks OTC and dietary abuse —. by of their bronchodilation instructions, ;Dietary with that are 1997 4:30PM during the Committee the when of real ephedra consumers. PDT; Food page 62 Alkaloids Advisory who were ephedrine for according The containing Ephedrine members use used not great. supplements by careless and Containing to label problem, alkaloids, with is RE:Docket No.95N-0304 ;Dietary AMOUNT Supplements OF EPHEDRA ALKALOIDS AND TOTAL QUOTES FROM 1996 FOOD Containing DOSE Ephedrine Alkaloids PER DOSE PER DAY ADVISORY COMITTEE TRANSCRIPTS AND COMMENTS Although FDA should total 20 we have not dose DSHEA dose, for this The most of This with is Unless safety for (which is per day is of FDA not limit realistic dose set the hereby provide allowed to by when the with limit a at further be will be and causing multiples of mg. dose used as directed. total by ignored the consumers to -- thereby = +-31 be alkaloids safety of 60 mg. the avoidable per FDA’s thereby warnings multiple causing be to consumers, take form dose consumers; label of We believe current dose per cannot ephedra by other 17 mg. mg. the accepted current common 20 a total common standards , a by in deviation 110 the ephedra in in with of food food a met that higher for 20 mg. generally credibility far not found (standard demonstrated will than a median (we consider that has is doses set DSHEA) unsafe as the than supplements FDA safer dose and and harm. Version is per limit reactions doses and -- adverse 206 Dr. Love summary consumer per limits as having dose too many I pg. as to why should the dose much per sometimes adverse 30 mg. reasonable A 20 mg. instructions, a FDA and the In the irresponsible), reducing we that though needed limits 8 mg. instead their is is comments to day, already allowed proposed Vol. on unreasonably dose record. per even by dietary a dose grossly true given reg.). but reason are a mean considered —.— proof form . are mg. several conclusion. supplements that alkaloid 60 dietary dose ephedra fundamental burden products made of 24 mg. per day, lng. per reasons limit already event used of the FDA reports the of 12 August, analyses IIwhere product 1997 so 4:50 we on had that PM PDT; products associated information we could page on how calculate 63 with the the RE:Docket No.95N-0304 milligrams at O per all way ~ ~ ephedra-containing zero ephedra vol. the over plus ~ minus products by the product in amount as to its incidence because of the nature drug individual has of is been So which for magic. going to even if we going to control and that’s not going of the of the to increase in customers switch of if from to my the deal rather with down the of by of expecting people exercise for ephedra a particular drug really that scientific for the the looking amount looking than firm, somebody’s bound to give some them sort free of behavior, day set is their that dose OTC limits drugs are any purpose at any ephedrine and 120 mg. of theophylline, methylxanthine, will FDA’ S far occure 1997 _ 4:50 lower, if to an OTC product —_—_ cannot per limit. of 12 Augustr _— more for capriciously safety consuming than difficult limit FDA mg. anyone label and way why 24 stimulant ephedrine that been to be easy.’! and 24 mg. like —— —— had I’ve pharmaceutical enough we’re reason dose available arbitrarily __ over major per contain Version event and I draw from who’s take ‘II think scientific me, actually medicines And be simply caffeine was supposedly rest to are very ethical effect A second ———— an a person that the reactions, herbal drug, effect.tl that are in the readily dosage an adverse were safety alkaloids mg. one product mean presented people adverse by looking recommendations. 8 with Alkaloids of the reports.” produced not at from (!!) One of the What relative reports they’re that ~ it. Vol. I pg. 153 Dr. Ziment II.*. the patients who are taking is The Ephedrine say. having adverse magic, range 50. associated that without conclusions standard Containing 234 Dr. Askew information impressed this to FDA doesn’t II pg. “From up alkaloids ingredients?? Supplements use, ‘1 the products consumer the approximately ;Dietary with Rule but current with PM PDT; higher a 150 dose it mg. is lacks ephedra doses page supermarket 64 per not a day only reason; no supplement of ephedrine RE:Docket and No.95N-0304 ;Dietary than methylxanthenes Supplements the Containing Ephedrine typical ephedra products in dietary herb Alkaloids dietary supplement. Vol. II pg. “If we are 104 Dr. Ziment say ma huang unacceptable want @ take counter these and the ephedra A doses in does or would go to MDs them major ephedra labels the industry teas. occurred, harm inherent Vol. II pg. “If you ~ the the Japanese ~ ~ ~ Q m that ~ minimum then should prescribe impose to by the Rule the provided if FDA original forced labels precautions. FDA’s used allow doses be regrettable the the traditionally required interaction K @ the more you had If this proposed find Rule, find that millicmams concentration tablespoons, Version of 12 August, ~ ~ A therefore 1997 4:50 take not @ took cut ~ @ w ~ averaqe = PM PDT; - Q ~ that - ~ ~ that page ~ ~ 65 a probably huanq M sets which weiqhed ~ say no matter ~ ~ ~ 9-qram 5 crams, 1.2 * and you source YOU Q A ~ ~ averaqe ~ ~ around commerce, tablespoon @ ranae the x have huanq most Q ~rams, ~ U ~ based official seen, ~ ~ ~ Q that tablespoons You will the two you you’ve seen that moderate, of Actually I’ve tonq ~ range S warns. is the only will the that huanq of values @ m E .6 percent, Then aw proximately qettinq ~ is range percent. ~ over-the- people in traditional ~harmacopeia pharmacopoeia which these myself doses because practitioners dose. ‘l “If you take what cannot legally caused can use k ~ there minimum, is route Chinese You used Q@ and ~ 105 Dr. Croom that formulas we think FDA It would be harm people eDhedrine patient the products this that in the herb. take ephedra the and no drug it would that than FDA are unchanged. few if any warnings orthodox supplements added) that lower concept the (emphasis reason to take ~ the message of grandfathered the @ ~ evaluate it is far herb create have it give products?” is that ephedra this druqs have third marketing and ~ You are tea for you take ~ w RE:Docket found No.95N-0304 most physicians com~ounds.1’ The USP for ephedra on the US market the observations Vol. II pg. ~ ~ Ephedrine ~ for the Alkaloids pure herb is at experience is between least is that 1.2 and 1.2% most ephedra of the herb 1.8%, in agreement of Dr. Croom. 172 Dr. Croom I’The Chinese [ephedrine herb itself alkaloids]. means you So Containing added) standard with from between Our own extensive available there. Supplements usina, (emphasis alkaloids. That ;Dietary I’m others, An have between average between taking not has 6 dose and traditional to justify generally of the 12 herb but use, of what to say 2 percent is milligrams long-term the use, 1 and 6 grams. alkaloids do we know for safety where are the numbers. . .l’ Incorrect math. 120 milligrams Vol. II pg. Here, Dr. content Fong states that required] the though German 1 to contains between per pharmacopoeia of 0.8 percent, to a range Dr. Fong ephedrine Commission 6 grams of 0.7 and calculates likely is the Chinese in ephedra a serving, a more of herb 60 and 219 Dr. Fong and This 6 grams of alkaloids. prescription “Japanese The dose only content, dosage and ephedrine not less of 7 milligrams refers E to the that the alkaloid than.11 to 48 milligrams 7 milligrams. it calculates [no to 12 mg. With to 72 mg. per dose. Vol. 1?.. 44 Ms. I pg. published .we containing due to also three system products Version .— —.. for by the evidence Removal proposal events, that some reporting a products containing these Bowen @ of 12 August, ._ 1995 bronchodilator one DEA being under [emphasis misuse m was not proposed were in suddenly 1997 found remove from diversion their and current in the ephedrinemarketplace difficulty rulemakings, our adverse and event products” because 4:50 use added] ~ to after 50 years to be unreasonable PM pDT; page 66 or so of use unsafe when RE:Docket used No.95N-0304 their event FDA mentions ephedrine FDA members this previously alkaloid deceptively proposed removal being was diverted the for Note, members even while removal that not as a precursor from of this Notice, previous because illicit the of the in the Rule impression reasons, data that (and failed) Alkaloids is in the OTC too, bronchodilators safety for use all it to Committee for it. false Ephedrine of products deleted proposed containing leaves FDA to supply asked Containing of misuse system? and refused Committee Supplements evidence reporting database though was What as directed. adverse ;Dietary ephedrine blackmarket methamphetamine. Vol. I pg. !Iover the mg. 45 Ms. counter bronchodilators of ephedrine, Primatene theophylline, containing and Bowen not to exceed tablets, still are OTC human pseudoephedrine is I pg. “Most 60 second so major version 12.5 the plus are to 25 120 mg. products ephedra of ephedrine. reg., and of ephedrine market. (a racemic of dose a day.11 24 mg. the (the metaabolite phenylpropanolamine Vol. on pseudoephedrine single 150 mg. containing phenylpropanolamine principal has alkaloid) norephedrine, The maximum maximum OTC the dose of dose of is 120 mg. 46 Dr. Jasinski of the concern (the drug of the DEA abuse expert) is not with ephedrine at a retail level.lt Vol. I pg. “Now, 72 Dr. Askew also OTC drugs reports the as the question.” Vol. I pg. “TDH [Texas Dept. 1995 that we time, food been raised the same products are, as to whether incidence and or not of adverse I think this the reaction is probably a 73 Dr. Culmo in October Version has are experiencing fair adverse question of Health] to the committee’s indicated reactions to of 12 August, provided that TDH oral working had 4:50 PM PDT; written group collected ephedrine-containing 1997 and on ma huang. 900 products page comments 67 reports for At of Texas RE:Docket No.95N-0304 citizens; that and 500 from thousand was ;Dietary 400 from of Containing over-the-counter food products. reports Supplements We now have injuries or ~ Ephedrine OTC druq products substantially adverse Alkaloids more events.t~ than a (emphasis added) Vol. 162 I pg. asthma ~ and other reqard $11 ~ patients, w what ~ and equated treatinq asthma have should ~ Q use of ~ Q ephedrine ~ dosaqes ti u in the the times ~ treatinq condition Q startinq equivalent w ~ that ~ secondary ~ time. four dosaqes dosaqes make lonq ~ know three those those and Z think m~. underlvinq ~ those And chanqed reasonable, @ the asthma druq. ~ their MQ on diseases) between whatever safe (expert been ~ rarely 2 think - x somethinq A@ k has ephedrine ~ Ziment respiratory who somebody dose Dr. u dose dose ~ @ ~ (emphasis ephedrine.” added) Vol . II pg. 165 Dr. Ziment II. . .this implication that hazardous, as long-term vol. fashion. II pg. “When as opposed at this physician with pulmonologist of ephedrine obviously I just than seven seven days less than days in don’t see the evidence could some be sort of for that.i’ 240 Dr. Katz I looked a to more back question, ephedrine in the for children much better I had since to divorce as a my experience practicing pediatric late ’70s and early ’80s we used with asthma. been drugs, but we It has saw very few a lot supplanted serious by adverse effects. “ Vol ● II pg. ‘rOne of working total the things group] was e~hedrine cardioactive &o_ Version 105 Dr. Croom was ~ one ~ that we certainly alkaloids, of 12 August, when e~hedrine ~ thinqs 1997 that w potentially ~ discussed laraest that 4:50 was PM PDT; in the committee You set the beinq side level seen ~ effect discussed.” page [1995 ~ the beinq most lower “. ..there 68 ~ was RE:Docket No.95N-0304 consensus also also certainly forwarded combination level, the that ~ of between that thinqs like caffeine ratio--this ~ even H of what though and Ephedrine I and is Dr. Tyler: was used fi w were ~ fi unknown there this were dose--should was Alkaloids thinqs ~ individual because data, Containing Tyler Dr. charman, Q 20/25, lack Supplements the to with aqreement ;Dietary ~ we some q felt data.” 10/15 like in (emphasis added) We agree total 25 mg. or other Vol. Dr. ephedra caffeine or per day. II pg. 57 Gordon then decided I Pharmacological Basis and I repeated milligrams per Hospital to Association’s children 12 years 12 years every Vol. of three old if a in caffeine the with and product maximum of Formulary and four ephedrine is dose hours is for a in which the their book, ephedrine ... looked listed 25 150 the to quote the from ‘For usual recommends this self dosage the every American medication in is 12.5 25 on ....‘For children safe 6.25 to 300 American “It goes at 50 to is 25 to 50 milligrams is... older, considered in found oral Formulary adult dosage ?II “Another is Gilman’s, “I then four hours. “t age, ephedrine is no dose what usual to Hospital hours. every at and ‘The dose. ‘ Hospital milligrams per of Therapeutics, ‘The usual four look Goodman’s Association’s following: three would every day mg. if there methylxanthines, quote: milligrams dose 20 mg. Peterson bible, follows per 10/15 other pharmacological as and alkaloids doses I!And I Croom methylxanthines, contains three with 12.5 to 6 to milligrams four hours. ‘t’ II pg. “Another 58 Mr. study. This 1993, Obesity Peterson and ephedrine/caffeine treatment are withdrawal from and maintaining transient have been 1997 International ‘We is safe and of 12 August, the quote: combination minor symptoms comes I in improving effects Version one conclude that and effective weight and no PM PDT; loss.’” clinically page of the in long-term observed.’” 4:50 Journal 69 “’The side relevant RE:Docket No.95N-0304 ;Dietary Vol. II pg. 75 Mr. Appler II I difficult find it toxicological should be basis per milligrams single experts. its dose, last ephedrine among bronchodilator October [1995 such are only supermarket any or way occuring in tablets, the ● This of II pg. 16 Mr. testimony probably felt levels have parameters of Vol ● per II pg. “What preliminary no appeared.” ephedrine walk then use into or of a misuse reactions abusers) was Review test a good were Primatene Primatene tablets were dosage. .. was serving size an for a clinical Boards study of Harvard and go through would not for these studies unless they they possibility that serving protocol the protocol protocol or going to be appropriate included at and at least probability tested, safe least 30 level. that the about 25 . .. the milligrams 25 milligrams of of ephedrine size.” 111 Dr. Ricaurte I’m puzzled on the products Version more reactions, can driven of far containing dose of users the adverse have an approved the per thousands drug and is Prochnow ephedrine per alkaloids would day, ago. approved milligrams caffeine a there of high ‘l’I’he Institutional on that them of it as.” use have significant than alone concerns ephedrine: Vanderbilt If buy per daily anyone you milligrams despite tablets that and (rather long say, by FDA and levels literally for bronchodilator store 25 AD/100 capturing Primatene population, to present to for this 20 of or [sic, the group] millions meaning lawsuits at seeing of has wish. users be Alkaloids scientific as declared alkaloids, Needless but drug they off the market Vol would reports OTC, working Ephedrine inhalation is safe FDA has tried FDA that, by ingestion total tens system available them we the substantial Not that any compromised 150 a day, products. sophisticated health oral possibly the hazard llIf that were so~ injuries a 25 on ingestion that alkaloids, Containing believe my in But recommended to that oral] Supplements by is the apparent we’ve been discussing of 12 August, 1997 4:50 disconnect the PM PDT; between the last day and a half page 70 data and RE:Docket No.95N-0304 what several long experience members of some loomed as major going of with issues ephedra ;Dietary of to the was before [1995], as a issues, prior exists Vol. are very OTC benchmark with the a they contained Special Working starting point the in the we are Group on containing of why haven’t ...if OTC products issue “...the system? the or 50-year products.” products by our certainly reporting suggested I think dosage the ephedra apparent disconnect 111 Dr. Love the FDA alkaloids. reporting is systems focusing Thus , it other is products alkaloids. The different publicity admission may be period dangers of dietary product these other when one same is, you don’t there from a single products that that other adverse and the has the ephedra has been of no FDA the OTC products publicizing those systems been use phenylpropanolamine containing reactions reporting there of ephedra other and is cannot the alleged alkaloids. a know be may well adverse actually ingested. anything so let’s what compared that natural affect for just FDA ban 1997 4:50 don’t safety a find cannot PM PDT; out plus know even to listed what the a as their else is. products and batch-to-batch profile.” competent just products be or anything lot-to-lot doing to all may potency their ephedrine necessarily variations, can have reason The You their reactions, of 12 Augustr be ingredients. can good containing manufacturer manufacturer that of Love manufacturer another the This FDA ingredients from variability compare dangers supplements from because Version the 112 Dr. Love “The containing to in alleged the reports and and ephedrine by Dr. during product ephedrine pertinent concerning II pg. on containing pseudoephedrine, source are different reasonable ephedrine, And with is Alkaloids different.” The Vol. said Ephedrine is critical.” “Of course, are has effects, it the experience then II pg. with adverse Is as committee Containing ephedrine-containing concerns use, alkaloids, the OTC alkaloids. Supplements followup what say the “we containing page 71 on consumer don’t know ingredients RE:Docket No.95N-0304 that may have Vol. II pg. lrI want don’t (but we don’t feel that are of prescribed = orthodox taking or ~ Dr. Ricaurte what either of ~ Love, this on the “I — don’t ~ side basis have —— that data . (emphasis added) no people the committee FDA did not scientific judgment ephedrine alkaloids, as important effects due no major Version ~ ~ that in adverse ~ and I still recognized or even certainly feel the danqers us are drug ~ will from a have there G danqers ~ ~ ~ ~ comparable little actually reports the bit more recorded, even on the to taking the public a different as bronchial adverse data. legitimate is in of 12 August, with or be of used (emphasis 4:50 to that relevant, to very making a containing data identified was within fanciful than the adverse dose names bronchial added) page 72 range effects names as a bronchodilator PM PDT; meeting products different other Druc$s Q members. are some products 1997 this effects of dilator, very using when There indication this indispensable by Committee sort at from It is appalling clearly particularly effects.” people on these risks on the label. @ appeared that on defer Drugs this and requested is printed but, I about give vol. II pg. 116 Dr. Weintraub 81...there are no serious adverse SO, ~ to. ephedrine And Q lot can provide information indicate reported over-the-counter hearinq members important mislead the referring 116 Dr. Love However, occur Alkaloids products.” II pg. that was nature. perhaps on a year-to-year that.” Ephedrine involved.” phenylpropanolamine. that Dr. ephedrine Containing 116 Dr. Ziment information the been e~hedrine without knowinq druqs.” (emphasis added) “Well, inform know) understand agents II pg. vol. what I pseudoephedrine disconnect Supplements 115 Dr. Ziment to follow-up dangers Vol. ;Dietary that which that may would dilation. there are RE:Docket No.95N-0304 ;Dietary Supplements Vol. II pg. 134 Dr. Kessler 1?...the question about safety safety are in the asking context you are of a supplement for. data quite information Vol. We are not exactly on the safety relevant the same.” system with deaths asking you today is That’s what safety in for of ephedrine to the are which intravenous ‘1..death very essentially amphetamines alkaloid we the containing interpretation of dietary abuse incidence is similar in to what out there.” Vol. 68 Dr. McCausland ItAnd I support milligrams per dose, Vol . II pg. “What safety supplements. which II pg. “God created amines as with a a certain result you are describing last amount, of the for all the other conclusion science The filtered facts don’t [1995], 25 change. 1’ through political considerations, days, or he rested at all. 176 Dr. Ziment the world there’s in seven that’s where no other the inspiration pharmacologic on the for seven reason that Amen. Version the 100 per day.” science and I guess but . ●ost death.!’ than Group’s on the amphetamines. control causing less Working is compromise. is is not for of effects it 68 Dr. McCausland changes This the their infections supplements II pg. even sympathomimetic result and as a result rare Vol . I pg. 68 Dr. Davidson II.. .if the products contain from, you to a diet. on ephedrine-alkaloid-containing cardiovascular day, asking Alkaloids I pg. 67 Dr. Jasinski (a drug abuse expert) II. ..if you looked at the data on phenylpropanolamine, looks Vol. we’re Ephedrine of an asthmatic.” But the OTCS context that Containing of 12 August, 1997 4:50 PM PDT; page 73 seventh days I know came of.” RE:Docket Vol. No.95N-0304 II pg. since in consume, what, 150 product, maybe a way, 15 pulling making the an (Federal Advisory ingested criteria, per that is a fail this FDA to require even milligrams Canadian looking a 32 experience for more This is McCausland Vol. dose, the am of just decision in accord the many with way” APA is and FACA substances that capricious 10X Furthermore, safety DSHEA does factor. the recommending, dose, which and Some of I of that is is at for that for is going total the low ephedrine 8 hearing with the when I’m here...’! sort of other close politcs that observers disgusts of the both Dr. FDA. 155 Dr. Croom “TO enhance — xanthine some at safety and daily, daily. and and most II pg. 40 Canadian “Canadian both a 10X saety combinations, not the of per model and water. 10 milligrams to release the again very Moreover, doing sustained but as arbitrary and allowed following the far Act) . oxygen alkaloids of Alkaloids added) is so Vol. II pg. 154 Dr. Croom 111 would recommend~ if I was end Ephedrine is the food, violation Committee on capricious, in also would not authorize for this and ephedrine day figure.’f (emphasis including ephedrine Containing factor, day Moreover, this per safety is arbitrary evidence. drugs milligrams admission that OTC 10-fold as.a involved, are the milligrams that Ah, Supplements 189 Dr. Wang 111 thought is ;Dietary safety~ ~ think alkaloids incrredients, ~ ~ from the ~ form, course, ~ data @ date stimulant that are MAO on Vol. II ~ would laxatives, inhibitors.fr ~ ~ ~~ (emphasis added ) We, like methylxanthenes alkaloid per alkaloids, original total Version .-—— Dr. Croom such as caffeine dose limit, whereas dose ephedra —.—— per 1997 of dose 4:50 20 105, with mg. Dr. allow a lower ephedra total Croom’s ephedrine is thoroughly PM PDT; would in 15 mg. methylxanthenes, suggestion alkaloids of 12 August, in products 10 mg ephedrine without limit pg. in ephedra pg. 105 25 mg. appropriate. page 74 We RE:Docket also agree course, Vol. “I No.95N-0304 that no MAO II pg. want to then we doses what we’re and do these kind is there that of that instructions poses It risks. Hence, single dose FDA be than now FDA) it and this and the people we’re doing, those sort case in to kind of are we 2 of quality banning we might very ephedra herb wants by products only to is the as well to quality label to those these alleged permitted dose and thereby to disappear label permitted of the benefits consumers, of using causing from and per risk the daily none possible products prove reduce not poor unreasonable total products the these market. door. last you’re for being a probably this, going we know couple and give effects, maximizing to wind of total just doing pharmacologist and looking caffeine Version to burden label reason ephedrine, milligrams reduced or down only what herb 40 to 60 milligrams psychopharmacologist the in 2 days, if we know and its obtainable is that from about of 209 Dr. Jasinski The again, levels, these meeting], in which of use so that (to the Vol. II pg. II.. .my view over meet is a ban by the back day. of I think market has using permitted of days will troublesome per cannot and FDA a substantial the number any ephedra evidence of no more and, 10-fold and If we supplement, unconvincing This Alkaloids laxatives any group Then to be the it. down restrictions because ephedra Ephedrine way?t’ banning DSHEA for doing, it. going vote us. of as a good But , the label stimulant working really ahead go and vote using no come 1995 tell go we have can for use under the industry control, be if that [since with drug whether levels milligrams, the should Containing inhibitors. see months from there Supplements 190 Dr. Blackburn recommended 10 ;Dietary that of from years it to people at about at this ephedrine this and and in terms studies that up with you can coming have take 1997 4:50 PM PDT; between page we know been done anhydrous cocaine-like .“ of 12 August, back clinical of what and get amphetamine-, 200 milligrams, alkaloids a which a dose 75 100 and 200 RE:Docket No.95N-0304 Right. Note NODOZ is like effect would experienced probably that 100 Supplements the FDA approved to 200 mg. mg. noticeable coffee just not most before, experienced adults an unpleasant reaction, have avoid one 10 to would people are at this using as to Alkaloids in OTCS overstimulating adult most adults herb before. coffee who in had the not U.S. However, in if they had and, of amphetamine. 12.5 keep the caffeine unwanted tried Ephedrine it. 15 milligrams, look of to an as Vol. II pg. 210 Dr. Jasinski l!OOOsomewhere about 2.5 milligrams to about dose ephedra already Containing An be particularly have the U.S., ;Dietary milligrams, it average in this ..is equivalent of ephedrine. dose or maximum from October range sort of of So what caffeine dose. II Vol. II pg. 1’1 think are doing loss down because for. ~ safety, and of a marqin —— g mar~in and ~ we’ve later, 10-fold, a indication leaves just already I’m not ’95 gone until from quite sure an here we estimated on what basis 222 Dr. Ricaurte issue purported that this.” II pg. ?!With the — — telling 10 months level we’re Vol. it’s 8, 9, safety 221 Dr. Ricaurte what @ with, well, suite ~ risk/benefit ~ ~ use heard are what clear frankly, when safety I’ve Purposes there’s of SafetY, — ~ ~ the @ have left really this answer don’t ~ beinq .@ ~ I’m & somewhat have ~ afternoon taken off heck are ~ @ that, infinity a perceived @ the then @ the because a have some that all table ~oinq a ~ W!2 ~ ~ marqin ~ benefit.” ~ can’t m (emphasis added ) The that FDA has the committee of ephedra made this disregard for those loss benefit, of course Version and of 12 August, any evidence purposes sold : weight then conclusion for which energy. even 1997 When small 4:50 risks PM PDT; inevitable by concerning the efficacy it is being you will cannot requiring most widely consider any seem unacceptable. page 76 RE:Docket Vol. No.95N-0304 number ‘serious sure 3 adverse that [the effect there’s Containing possibility ‘of in one it’s entirely at many least Ephedrine significant Alkaloids can is, no, I can’t, a fair question with regard harm’ and individual’]--I’m that compounds so the answer requirement, per Supplements 222 Dr. Ricaurte II pg. “Question ;Dietary but not satisfy I’m not that sure to the ephedra that alkaloid se.” And it is not the definition of harm mandated in DSHEA, either. Vol. I pg. 145 Mr. Israelson II... the standard you are asking harm, which has at that arrived which ~ definition has harm withdraw the that by dose 15 of chosen Rule, curious its definition to to charge that re-convene fits within two within the how you subDarts, the Committee intended the the ambit is that orthodox by law.!! with Congress, Committee, of Congress’s less period of time looked at the that dosage is harmful.” Vol. II pg. 236 Dr. Wang from ephedrine children. literature of safety? the OTC times because What and a That it’s of day reach will, safe I don’t level a FDA a new and re- be adults the 1997 4:50 PM PDT; used it for a that way. evidence that a 10-fold basis page and baseline if used for, alkaloid.” of 12 August, been minimal even took day always about--a see much is just per has for should I certainly I did maximum as such, in a dose and I believe I’ve margin 3 for for the orthodox, prolonged ephedrine, physicians milligrams proportionately Version simificant 231 Dr. Ziment prescribed factor b is a new Rule. II pg. “What at just specifically contrary “SO my recommendation dose I’m from the statutory FDA of conclusion Vol. look added) Because propose to sub-definitions, definition, different (emphasis must two us 77 safety again, RE:Docket No.95N-0304 It would the market fold authorize Vol. ‘lThirdly, have fail the I think there to be very in people water, tenfold Ephedrine would be on the basis sugar, safety a 10X safety that I and test. Alkaloids left on of a 10- total DSHEA margin, of concerned about athletes underground economy used manufactured daily does not either. health laws that historically and is being in, have the they now got a whole imported which those and driven watching have than coming made because We pure was that me steroids less which that’s were creating and uncertainties.” Dr. Jasinski that amazed these. pharmaceuticals both decisions passing using are problems Remember what which been made anabolic which as have people with point I have think steroids public what to be taken cautious. underground. being consider is a telling anabolic are Containing 249 Dr. Jasinski involved things had the FDA to impose II pg. been all to Oxygen, factor. intake Supplements interesting if all products safety caloric you be ;Dietary is an expert on drug abuse. Heed his warning. Vol. 249 Dr. Jasinski II pg. ‘~And I would think come a position in with going the it would to do voluntarily which better they and that It would standards. be to can this be much encourage defend would better on industry what they’re be legitimate than trying to to to set impose a policy.lr that Far better, and if it makes a rule any rule will work. than it prevents, Vol. II pg. “We’ve and got talk Vol. Version and points This enough one won’t. The guns It will result FDA seems to think at enough cause people, far more harm at the FDA. 250 Dr. Croom find about how II pg. effective. an all too common to are benefits far more a better do we coming here way, impact I would the and not just public say, to health come because risk. . .?! 255 Dr. Dentali of 12 August, 1997 4:50 PM PDT; page together 78 there RE:Docket No.95N-0304 !fwhen I came sense got one, the to is to adverse consistent October those that other known ones those, And I feel the Vol. levels not, were risk for it is the danger II pg. 262 Dr. Ricaurte has to regard regulating something Vol. II pg. ‘II think abuse, find recommendations, 10 or particularly Version and eliminate to with only to look all the and others, chronic that that very to look the and use. was on beginning regarding at eliminate the herb from use with adverse traditional botanical.1’ from one extreme as a product, or group Those a dietary very is adult have the put medical into not been may that not be profession a Americans cynical ingredient and not be over-regulated, FDA that of being or in the position of over- wish use under to defined.tt 262 Dr. Ricaurte as long I this the advisory conditions. swung by consumers where safe this in reports, traditional of using recommended and me at are combined I feel the that were resulting to to objection. scientific .— for cogent position to presented a and abuse a handle to do ones and exclude and I use members made those done at those were were look that So when be to look ephedrine were Alkaloids common- respect with few ones the I wanted would that clear to have us to determine be used from that wasn’t was a at the that A very to trying by is with to eliminate ones that as not, Ephedrine products. events, of ephedrine and to include that what should are and ones these For me, that resulting the with mission particularly to look at the my adverse proposed stimulants “SO the pendulum a that were Containing are consistent for me to be able effects forms were exclude important ones that extract to those, that the to look and at the that the herb risk recommendations. with or the that of the of reactions eliminate the reduce version [1995] Supplements I understood analysis October the here~ updated rigorous ;Dietary down as the concern it somewhat, well, to adept of 12 August, for some we’re 5. in As again, going a 1997 4:50 to PM PDT; is misuse disingenuous to limit consumer, mathematics of the use the dose I realize don’t from have that page to 79 if and make 20 down to now be the ~ RE:Docket tablet take No.95N-0304 or 2 or frequency capsule or I take 3 or of well-intended looking I safeguards .’l They are dietary I take I appreciate So the while what of the use who be predisposed don’t think risk of efforts label by that are instructions they’re or abusing of the effective will destroying and in terms particularly they I“ by a population to misusing are Alkaloids considerations recognize ineffective; harm of all the I Ephedrine 5 milligrams, of the product those than worse only dose the reality may Containing contains 4. and the credibility spoonful suggestions, of individuals product, a Supplements use at the increase ;Dietary substantially the integrity and warnings and on ephedra supplements. Vol. II pg. 265 Mr. Israelson II...I share the view that has been product, you’ll drive it expressed underground that and if you ban this create a bigger problem.” Vol. 11 pg. 270 Dr. Woosley II. . .as I think you pointed risk/benefit ratio you can out, Dr. establish Ricaurte, when you there don’t have is no a known benefit. ..” There refuses are to benefits allow guaranteeing a known the to the Committee proposed Rule Committee; to that the consider is not FDA them, based on just thereby reason or evidence. Vol. II pg. 274 Dr. Inchiosa II...in the experiences in Ohio, information drug largely counter number of the use something it from was from that not a nutritive young ephedrine I heard by young preparations, 11 pg. Version get preparations. counter Vol. collected the and the that Canadian people study, who are hydrochloride statement abuse by young difficult made was process 1997 PM PDT; page abusing the over-the- that from of supplement.” 4:50 the from 197 Dr. Kessler of 12 August, even 80 a large over-theextracting ‘ RE:Docket “It’s No.95N-0304 [the record with judgment before some, the last two both others, they’re in the before starting quality as and, reviewed. removed II pg. I walk I mean high standard already that of about into that we a store are have safer and than have need about than of dietary FDA has on food Dr. Version I been two days. literature that but it’s the think that the is of very poor certainly.11 Love, has event done risks supplement least and not yet safety been data peer has been as ephedra foods badly to risks safe of herb as I as a consumer, products, have the in my hold foods them up every diet to a very poor dietary supplements in common form. The bottom beliefs about the presumed be educated foods supplements, a very these so I would unrealistic the which safety.” job about is of far are line is safety that. Educating greater importance on the basis of the record, of providing needed yet information to consumers. and your data (emphasis of 12 August, been the and the particular interpretations we’ve heard, II.. ●nd ~ essence ~ ~ review.” the over has last last two days sells Vol. II pg. 157 Dr. Jasinski I!...the critical question has deaths that expertise, OTC adverse that at shown, consumers the upon account. presented the presented. the a dietary of expected consumers that over two days, by to supplement much foods been been the individuals into information and on by the FDA. to believe As be that Alkaloids 204 Dr. Chassy “We are talking reason has own over vital that their the last admitted take draw based of different We’ll can Ephedrine ephedrine] alot group has supplied Moreover, expressly when as is over But the data and Containing of it’ll working with them base some, certainly familiar record We have information For they level expertise. be the days. Supplements a safe individuals. it’ll presented Vol. on a lot of different For For ;Dietary relationships interpretation and there has been scientific culture 4:50 PM PDT; these versus the a conflict.” ~ ~ page 81 added) 1997 of have Deer RE:Docket Vol. No.95N-0304 II pg. ;Dietary k have vou prepared collected it, how You made, have aqencv ~ report from submitted (emphasis II pg. data even this committee ~ to and @ And, ~ Your what internal ~ review have submitted the in the @ weekend meetinq were do @ a or that submit ~ ~ ~ peer that Vol. II pg. 248 Dr. Jasinski II...1 have been disturbed to some extent by Where either all scientific of this. of did she write making discussions.” scholarship like ...it~s this a report, available (emphasis the analvzinq the review reviewed, vou taken W they peer in terms vou’ve this ~ a added) is that that. through YOU ~ information rushed of how within ~ were schedule review review. ~ (emphasis tight internal ~ SUPP lY ~ ~ here.” such to peer that, just lack Alkaloids added) So they without do? data< conclusions similarly, committee intend over conclusions Ephedrine 158 Dr. Love course, They ~ ~ this aqency? @ q report interpreted ~ this Vol. II we time you outside review?” Containing 158 Dr. Jasinski “MY auestion and Supplements or data and they what is really scientific you their intended start to the quality I asked it reviewed, before have into the meeting question was didn’t Dr. was Love it peer getting these added) Vol II pg. 26 Mr. Betz 1!...although I pointed out last time ● three products still in the report The report carefully same for or no dietary whatsoever. must be noted Version absolutely as part that purged ephedra little contain the of data alkaloids care supplements The that FDA’s of this FDA to that report 1997 4:50 to OTC would never as given PM PDT; these they’re report.” to the drugs adverse contained that alkaloids, supplements, remove the FDA report of 12 August, larger provided pertaining taken in 1995] no ephedrine as the dietary was [meeting no Committee was containing the but apparently reaction ephedra pass peer alkaloids review. to the Committee page 82 reports It would RE:Docket No.95N-0304 ~ the meet junk science. Vol. II pg. II . . . student also who product same Supreme 53 Mr. it has daily police the been dose the to cocaine, amphetamines performed which is most that the tests part m W a certainly autopsy report.lr and from scientific certainty quantity on the the of weeding product, Alkaloids out in the substances ~ (emphasis report that of product consisting of such and “It as at is all cannabis, that other results no tests substances Dr. Love were said not made q added) many is autopsy to a of death not in possible reasonable was to you Brazelica, deficiencies it containing submitted of Dr. Joseph ‘That the cause the findings of Ma Huang forthe times to room.” no the Those three according “Yesterday, Iff concludes: a these strange.” Safety took It appears of on all at once. hotel other [college warnings Nexus, contains sets individual addition, the declaration which determine some Ephedrine for all report performed. package report In presence very Committee toxicologist, companions found of the the dose or barbiturates. for were that the daily and another presence of their criteria clear his autopsy autoPsY ‘lThe Ad HOC twice were relating were Containing ignored incident. cannabis the reported that without that Daubert Florida] at least kava-kava noteworthy as part widely indicate report, herb Court’s in and took Supplements Shapiro died reports the ;Dietary the to degree ingestion ephedrine.’” the of (emphasis added ) Vol. II pg. 110 Dr. Askew “Clarification mentioned coroner of earlier found autopsy.” in which II pg. “The clarification (This there in the consumer’s Vol. the the was some refers question to autopsy as to what the information on bloodstream.) 110 Dr. Love consumer’s of the negative autopsy ethanol report and is that cannabis levels record. “ Version the of 12 August, 1997 4:50 PM PDT; page 83 are in the RE:Docket Vol. No.95N-0304 II pg. Dr. Supplements clarifies ephedrine alkaloids tested strychnine, the and for were Florida autopsy caffeine negative, cardioregulatory Committee Bass and Florida, on the who the lack Vol. suggest that of ~ all of and level product.” that ~ this Vol. II pg. you will There none doubt.’’(emphasis I pg. 59 Dr. Davidson’s Version Appler and from 20 the perhaps from the Ad Mr. Shapiro at year old not hotel from as clear-cut rooms or analyses.” on ~ for etc. , and (emphasis anything attributed ~ it added) that ~ else to ~ exception alkaloids show Calvin the by the have autopsy report? in the autopsy report. McCausland 20-year Dr. in are doubt. reports of amphetamines, Mr. ~ levels old find reasonable it’s reasonable Vol. ~ directly was not at out and k FDA data “There you .“ cocaine, list the were use this h analyzed of ~ @ ~ added) the look spelled blood ephedrine 65 Dr. Orem, Utah II...if you Virginia was reports “NOW , where didn’t said been to compounds coroner (emphasis Why report, his the product.” hiqhest situation other a long found 229 Dr. Love “Actually this his from referred toxicological I pg. negative, Alkaloids and others. of Ma Huang also which while including drugs, Safety Ulman, the presence with Ephedrine report, positive, Vol. I pg. 229 Dr. Fukagawa It...in letters that we’ve received Hoc Containing 147 Dr. Love Love others ;Dietary other Thev fi three deaths took ~ in doubt. Borzelica, those from That ephedrine have — been — Q week ~ ~ and the Medical that Prochnow International, reasonable the volumes that — tissues Enrich Florida from Mr. you autopsy. doubt has College of have listed before, autopsy before that ~ reportedly. Reasonable added) Michael Davidson, qualifications behalf of 12 August, of the 1997 M.D. and his NNFA. 4:50 review See PM PDT; of the adverse Adverse page Event 84 event Clinical RE:Docket No.95N-0304 Summaries at Tab case files these found case and 191 files, 107 that unknown F referred underlying 191 serious ;Dietary not 13 were of these lack of 22 were possibly adverse serious. related Containing Davidson. categorized to be for related; to by Dr. he not Supplements of “Of the to ephedra. information. the summaries. the events Of to be 84 serious events, I classified eight Thirty-four related, Alkaloids He reviewed event 84 Ephedrine and seven associated with I as were remotely were probably related.” P9 “ 61 “Six cases, deaths not enough assessment. of were present deaths on due individual had internal carotid of history whose a prescription associated from drug deaths were due on The sixth a seizure also loss. on the these an obese in due a very and was strong high dose a family individual on phenteramine, of these who to a left associated All the of Another female had possibly was for weight occurred She One of supplements old with Two autopsy. in a 44 year doses abnormalities occurred other an associated strokes. that multiple occlusion. of toxic and cardiac to In two consider individuals. [stroke?] occurred artery was death atherosclerosis strokes. death possibly three using to to consumption all a strong ephedra. provided deaths in deaths who was that related six autopsy artery stroke was due to sudden to male basilar fatal were associated was were ltOf the three possibly possibly information Two deaths ephedra.” ephedra, were Apidex, six ephedra possibly products.t’ [How high?] ‘rThere were these ten ephedra. ten cases cases, In four, another in my three information provided myocardial infarction, exists. of non-fatal to of these revealed normal individuals were consuming an there not In not three cases of ephedra infarction arteries. ephedra to enough with post-myocardial coronary Of related was association reports, high-dose infarction. were assessment. possible In all three angiograms judgement, reports, make a myocardial All three in combination with caffeine. There unrelated four were or remotely additional Version 17 reports cases, of 12 August, of non-fatal strokes. Three related to ephedra-containing not information enough 1997 4:50 PM PDT; was page cases products. available 85 were In for RE:Docket No.95N-0304 me to make an evaluation. association In with four individuals prior left remaining these of the women to cases were cigarette over but one with smoker, and before containing majority were of exposure to reactions. high-dose and one was product being a for All the per panel, do individuals EEG woman ephedra of appears two to thrombosis 105 non-serious adverse increases and dizziness. of dose, the one-third which have a adverse less These than of is with severe are I reviewed, these tachycardia, are expected These in greater that the low-dose potential side effects frequency ephedra recommended rate associated 15 mg. per dose. 1997 infrequent in the products. significant the toxic and seizures. pressure, products. occurring events all of 12 August, blood symptoms ephedra-containing the hypothesis not in cases. associations that a I am not of only products events As cases be the either of these or cerebral by with evaluation of ephedra-containing These cases, on follow-up. exception there these by coronary To test Version the ephedra-containing 15 mg. in a limited to be dose-related, containing Of a possibly high-dose possible effects reviewed seizures. noted hemorrhage. exception the two of as having on the infrequent nervousness, over only with characterized appear is unknown a The was remaining on or an abnormal associations Of the of occurred ephedrine, characterized side these intracerebral patients --the reports I made summary, adverse At least of was with emboli. diagnosed three inhibitor --were seizures a neurologist, are 16 of seizures possible was women as of women. use of these a male products. There In the she suffered lupus involved One these hyperlipidemia source other In one Alkaloids a possible cases, of premenopausal contraceptive stroke a positive case a possible and the inhibitor. oral One contraceptives. smoker of these history involve cases, a year as cases, associated hypertension stroke. on oral lupus associated the ten Ephedrine exists. possibly significant to be a cigarette positive ten Containing remaining products ventricle five Supplements In the ephedra had diagnosed dilated ;Dietary PM PDT; of with These ephedra-containing 4:50 dose products of the adverse the 86 1 product account products, page working events, ephedra products below but for only RE:Docket No.95N-0304 approximately events that the 7% ;Dietary of the adverse on low-dose products, were possibly related young woman inhibitor, who and had the Supplements events. there only product. a stroke was Of were to the other Containing who a 55 Ephedrine these two 42 adverse serious events I mentioned also year had one a positive old female Alkaloids was lupus who had a seizure. Based reports, on my I have Number working the one, affect quality are assurance day with the vast of ephedra adverse recommendation the The are to lower dietary two main the dose the ephedra of ephedra provides majority reactions the event of the ephedra supplement issues of the trade that appear ephedra and to the of the product. 15 mg. equivalents, [1995] those reactions of opinions: appropriate. The proposal per following and adverse review last year’s group associations medical a margin of occurred per both with alkaloid dose, expressed of safety serious products content based and that as on the to 60 mg. ephedrine fact non-serious exceeded that adverse these dosage thresholds. Improved good provide dosing will dosing permitted. The warnings and Vol. IfDr. Love, serving working product ~ can ~ against and group also assurance batches. would easily Because ~~ ~ mis-dosed recommended instructions. the those @ ~ use with I would by a very also smokers, include those history of you, terms appropriate on taking cardiovascular the oral or 107 Dr. Georgitis I have events of the a question below the ephedrine to how many of those Vol. 107 Dr. Love II pg. Version quality disorders. II pg. aadverse that and added) labeling contraceptives, within important, products (emphasis cautions seizure is that ephedra practices consistency consistency recommendation label manufacturing of 12 August, for median value alkaloids, out of the total 1997 4:50 in of do you adverse PM PDT; 20 have of serious milligrams a percentage events? page the 87 per as RE:Docket No.95N-0304 “We haven’t ~ have iniurv expressed only collect ~ our that numbers reports ephedrine of up of the FDA after m we’ve was usinq important Here, is a very receiving the poor such you have factors --where a sample --could levels you saw significant Vol. 11 pg. 108 Dr. Love “Well, unfortunately, but there yet don’t product are a number have but a cardiomyopathy milligrams, to be total case. total ephedrine alkaloids. just mean the best Vol. II pg. VerSiOn _. a No taking through data a single the of that it on the didn’t follow- have a lot examiner, where cases data cases the again, in and hand for consumer it at in that a death used case 10 we the to be are from what containing here, which appears a 10 appears milligrams or how that of what 10 FDA or how “appears” milligrams is provided the was using, that case knows on what of how as I stated of 12 August, — 1997 of total the much of the have some--I often. (to Dr. Love) case. I mean just so we we have.” I don’t to be else 109 Dr. Love —— amount admits those the how containing information 109 Dr. Kessler go that alkaloids product product individual “And “Well, of was II pg. a FDA recent As I stated mentions ephedrine Vol. total to how the alkaloids.” use the of on death, alkaloid. long-term product The use FDA here individual recent ~ reactions? all very information more long-term The ———.— all @ ~ concerning go through have including - the time a medical adverse I don/t * reflection have just what course, reports. you you of Alkaloids added) related Vol. II pg. 108 Dr. Kessler (to Dr. Love) II. ..you asked for relatively clean cases of confounding ~ question events Ephedrine because, that.’r (emphasis adverse This form samples consumed. that. Containing in that the consumer a very actually know - analvze is clearly of Supplements data relatively QQ able ~ This doesn’t ~ samDle ~ ;Dietary have all those 4:50 PM PDT; details.” page 88 RE:Docket No.95N-0304 ;Dietary Supplements Containing Ephedrine Alkaloids . Vol. II pg. 109 Dr. Kessler “I’m sorry.” This is a shockingly supposed to evidence concerning Vol. be “I’m trying now, seem best or adverse you have effects with where very you to have the of a same you’ve done the they number feel because for where as it stands But you do have alkaloids on there the of is fewer in them, market, adverse a [in relative public things FDA/s an you effects dose-response incidence], increasing health increase problem this and how showing that’s is related in publicizing caused not publicity in which supplements recommendation concerning injuries were by) the use of ephedra has to use resulted that going to to the change in and ma huang publicity during the has FDA pseudoephedrine, II pg. this period received for the asking people alkaloid reports in the concerning ephedra or phenylpropanolamine) adverse associated in The FDA’s warnings Diqest (pg. 85). repeatedly on network TV. There has Version us some of cases actually of this received not necessarily Vol. providing in?t~ Indeed, dietary gives products that is growing or how much reports cases is dose. of ephedrine those suggests increase getting to report on what .“ this the way best the board. Vol. I pg. 234 Dr. Jasinski II.. .you’re showing this increase project, the correlation, amounts fewer around relationship we’re information versus that all across high have which of of reactions to get at something reported, much of total one to see a dose-response products and their amount 228 Dr. Chassy I pg. we begin small (to Dr. Love) have been 1997 4:50 PM PDT; CNN 1997 also no adverse (but and events a Reader’s appeared similar FDA reports alkaloid (ephedrine, containing OTC products. 277 Mr. Guzewich of 12 August, with containing on July events page 89 RE:Docket II ...1 No.95N-0304 want running compliment difficult quality data Yes, the the quality hapless data of other have prepared but the in the side but they Vol. 282 Mr. them, have I think, to assess in the market levels. ..” More other FDA consumers for them poor consider point be any made safe choices than they for poor ahold the of and any should of MIs ephedra of FDA could had the data have had data and strokes and but did on the occurence ephedrine a committee products, available of benefits the and improve lap The events containing between should it safe of drugs for be able be at risk to consumers to expect different at normal information on for bottles to purchase use, and and benefits) to Guzewich, any must be expected for their use of products, 1997 labels consumers safer as unmitigated of 12 August, might and on the a product even ~ abused added) education virtually that we can reasonably consumers find products choose Consumers Version about data by Mr. at had data by committees quality the OTC into to present FDA a very Guzewich better of using has cannot ignore occurrence the is a far better to treat made and The in did not. (emphasis methods choices in FDA them adverse do of data. ..” information. not. have when and the did is more Therefore, shelf. important population comparison, II pg. FDA spontaneous effects 1! ...sophisticated failed on it The FDA should adverse the Alkaloids for 16 years reporting the to to and she kind dumping told that you can get and is then and a report on seizures not. which data on that by task Ephedrine trying doing and you’re quality, data available peer-reviewed, available poor Moreover, with job, decisions these the products. she’s It’s not an easy are committee, what it’s the only to make Containing I’ve been thankless and when trying on program. disease. and often Supplements Love Dr. a surveillance for food-borne you’re ;Dietary idiots make to assume at least 4:50 labeling they must for have can in the PM PDT; than by the do not final should ridiculous. responsibility to their page The market and some personal extending make decisions (eg., them. impractical and opinions, limitations a product is that in our that decisions that in by the FDA and given unreasonable dose so choice, assembled and 90 compliance RE:Docket with No.95N-0304 label instructions. supplement products directed, Vol. II pg. hard because DSHEA may sets us in court Alkaloids dietary when used as abused. for weeding withdraw the Rule, reviewed data to that damage in speaks for never meet again they the the [FDA] FDA it find of proof that case, and and again.!! data Supreme in to may and again Committee, are to do specific Because members need burden a data, relationship, they itself. science. Committee fits within of the because where the that re-convene quality especially to bear done out junk the they doing would criteria asked have the a cause-and-effect I think being comment meeting conclusion that unsafe in any way in a situation alkaloids above Committee from this Court~s Daubert of this, FDA must provide advance, the ambit of Congresses the thousands of pages sound reach will, peer a new and re- a new Rule. It doesn’t by be. noted staff to build find themselves The Ephedrine requires how badly have FDA need that ephedra FDA before no matter the they however they may DSHEA unreasonably members] blaming be commended, propose be Containing 285 Dr. Chassy and without the not [committee themselves Supplements Moreover, not to be safe “Several the ;Dietary seem presumably the the distributed meeting were questions questions and containing adverse dietary reports ephedrine of what seizures for to actually asked included deaths that read the are among FDA answers interpreting the meeting, Love Dr. the committee not have key to of by most during using what containing dietary questions the adverse (FDA) did not have or both. Version of 12 August, 1997 not do their available 4:50 PM PDT; were similar key either levels of amounts of . Yet, or before page cardiac ephedrine- information. homework These information reports. this of the supplements) are of meeting meeting. population products information judging the OTC did of them, numbers and these members the supplements that committee background meaning members the the as ephedrine-containing The each of materials 91 at in the Either the or FDA did at the RE:Docket No.95N-0304 PROPOSAL SPECIFIC The true U.S. not prohibit reasonable dietary the specific product. sold 1.8 grams (the amount of herb lot analyses total of 20 mg. used in this so that more approximately Version one is as the effects are authority to to This powers per of discussion to a containing one tablespoon on of product No ephedra the basis contains extracts caffeine no require labeling adjusted no used or synthetic ground in sensitive real ephedra of 14 August, a are other ephedrine, serving, 12:13 than an instantly of the alkaloids slowly releases effect and herb AM PDT; its reducing individuals. when different capricious, of ephedra 1997, herb herb extracts; is arbitrary, tablespoon levels a time-release alkaloid 1.8 grams rather blood substantially ephedra a . contains providing containing manner With that and and herb being is extract, slowly pharmacokinetically identical FDA formulations one tablespoon herb alkaloid of adverse containing limits ephedra there ground thereby Products labels license herb The and commerce. alkaloids) it the these Justices) statements have the First or phenylpropanolamine. ephedra the risk of ephedra Court or misleading, these Shaw the discussed Supreme does on of ground and whole alkaloids, & product, pseudoephedrine, much of of ephedra methylxanthines, increase hazards it by have Alkaloids LABEL considerations. in interstate Pearson serving soluble of FDA false application Commenters approximately are on to prohibit The that supplements We labeling Ephedrine ACCEPTABLE placed quoting authority disclosure Since (often misleading. considers limits on general statements Containing Constitution. constitutional and the length section Supplements FOR A CONSTITUTIONALLY ignore at some in a prior no the of limitations has cannot FDA Amendment ;Dietary ingested from regulating this product (adjusted page products them and contrary to 92 are in an to fact. contains standardize RE:Docket the No.95N-0304 amount of conservative grams ephedra compared (usually the following NOTICE: FDA new or more would more mix. On Stir the the three on, drink more than place. use. Do adverse drink use reactions WARNING: KEEP PERSONS UNDER serving a serving 20 the ALKALOIDS. mg. size of injury may cause THE AGE May taken total of 8 mg. or illness. heart cause anorectic or of 14 August, hour when attack, mg. total herb) . This before you duration care than For For the From then not take in a cool, provider 7 days. of use. dry of and TO OR USE BY RECOMMENDED bedtime. SERVING individuals, Consult asthma Use page your medications, suppressing) medications. AM PDT; Risk Starting in sensitive taking before reactions. EXCEED (appetite 12:13 Keep Do NOT FOR SALE before are A DAY! breakfast. lunch. of in use. more insomnia soon SERVINGS dinner. period. DO NOT serving breakfast. before not one before of adverse cardiovascular 1997, of THREE a health for with 18. if 20 to before OF CHILDREN. too use EXCEED a 6 hour risk water serving product OF grams serving Consult increases 1.8 serving closed increase before antidepressants, Version within this SIZE OR FREQUENCY. decongestants, to 9 propose 6.7 (contains or cold one OUT OF REACH if we EPHEDRINE risk DO NOT one INSTRUCTIONS: especially 1.5 by the FDA. a second lid tightly use may that TABLESPOON one-half drink one serving not of quite to on page (contains serving of hot drink a third stopping physician 1 and drink. days, FDA MANDATED CONTAINS approximately 4 ounces days, Keep Rule, 1 TEASPOON approved day, two WHICH recommended from briskly next next Add first tea, serving referred proposed FDA believes SIZE: is ~ DIRECTIONS: herb an unreasonable SERVING size tea of Alkaloids or death. alkaloids serving serving Ephedrine product: HERB . The this seizure, FDA’s SIZE:: present than TRADITIONAL per traditional for this SERVING alkaloids) ephedra the EPHEDRA ephedra stroke, to the of label CONTAINS Taking alkaloids) Containing Rule. basis MANDATED Supplements 5 to 6 gin.) of ephedra of the proposed On ;Dietary 93 drugs, of caffeine RE:Docket No.95N-0304 containing product. you beverages high (especially stroke prostrate within 14 drugs. Stop use product initial seven these final of by these or VerSiOn ——.— is drink oxidase) care or this tea inhibitor professional tingling if symptoms if sensations tremors, of allergy to other the it, than treated of day over to reduce the the of from once per a period of incidence of tolerance to the alkaloids. proposed rather Rule has been I!Caution, ‘1 as than for advice high blood disease, should checking are is listed with 12:13 seizure as We do as absolute your form of AM PDT; “DO care are at risk heart, due to prostrate be required 1997, health or if you diabetes, all stronger a pressure, conditions. first the from or nursing in urination Of 14 August, ——— per size alkaloids of the ephedra 43 serving ephedra times “Seek conditions but the development used contraindicated than increase by the FDA. psychiatric conditions expressed to respects: or difficulty (rather use mg. if you are pregnant being and due if sleeplessness, is designed page Rather absolutely these on proposed practitioner stroke, Stop three effects “Warning” 2) mg. allowing in several thyroid size 6.7/20. schedule Caution tentatively are serving instructions 6.7/20 This l)- or health of glaucoma, not (monoamine if history urination Do palpitations, occurs. CNS and cardiovascular modified MAO of this disease disorder, disease. your heart or reduce effects The in Alkaloids or lactating, or a family seizure call one-half days. adverse and effects cardiovascular difficulty taking Ephedrine develop. that day to the or diabetes, or nervousness Note the pressure arrhythmia) headache, Stop the stimulating or cardiac after use Containing if you are pregnant or psychiatric days dizziness, this tea enlargement, hyperthyroidism, nausea, Supplements increase blood disorders, occur. may Do not use this have these ;Dietary heart, disorder, enlargement.11 not not use believe if...;’ that contraindications doctor), warning page as we 94 we have have used RE:Docket should No.95N-0304 ;Dietary not be prohibited. It would not in the public interest in such as a way contraindications be Containing arbitrary, prevent the list additional required care or of or to prevent list. For professional any other permitted last warning “Taking necessarily and credibility may stronger warning: Taking would more stroke, seizure, warning should stronger this warning 4) We have professional drug. Such consultations customers unwise to to ignore take put a disregarded, disregard for alternative should you be are this allowed taking (appetite Version to other to asthma suppressing) of 14 August, for have be wit~in the will not this the a serving risk the FDA they user are other FDA’s much of 8 mg. or illness. heart this not attack, stronger prohibit to consult taking easily cost ~ $5o with a simply label that warnings important ineffective warning, or “Consult your medications, won’t one more; do knows AM PDT; or page It will a believe before decongestants, antidepressants, it. warnings. physician people to expect promote we their prescription It is unreasonable they 12:13 of is proposed. the the should is the size of injury it lack of that such drugs, yet, used more 1997, should because credibility serving but on used We do not believe action; say we amount been that warning. far health inhibitor inhibitor cause may warning an MAO may if this this generally we instructed care generally the the one that not minimum your that Worse recommended health will not an unreasonable required, than taking a prohibit their “Consult an MAO has reduce or death.” be never recommended FDA believes present than the Instead, “The being contraindication. than to additional from than believe credibility. tend statements. are taking benefits.” lacks warning or more more increase if you that of must than drug.1~ we is an absolute 3) weak use prescription 14 days both before a label but rather and FDA should require contraindications example, Alkaloids the warning contraindications contraindications stronger capricious, listing listed as absolute rather than relative. minimum Ephedrine for the FDA to standardize to or Supplements is be general As an that we use if anorectic cardiovascular 95 RE:Docket No.95N-0304 medications “Consult taking .“ If your an Rule care or any which is Ephedrine the to the label before other with Containing requires practitioner be prefixed Warning:”, Supplements FDA inhibitor will mandated the health MAO statement ;Dietary use if prescription truthful protected Alkaloids carry you are drug,” this non-misleading speech under “FDA the First Amendment. 5) Users instructed nausea, to adverse call serving temporary insomnia, warnings to carry truthful protected one ephedra as such. This per size voluntarily authority the Version real call the to ~lstop matter their or far like tingling more serious serious to diluting FDA’s Rule it will an doctor a potentially cost be to make minor of mandated major requires be prefixed Warning:f’, the with which is Amendment. label label FDA mandated identifies contains and two FDA mandated different serving identified provides a information Indeed, be voluntarily placed of this without misled it on to prohibit source a to as such, traditional and an amount of serving. non-misleading. would instructed to or warning, This that of be life-threatening palpitations, If FDA likely instructed symptoms “FDA the are stroke, the First label: Identifying manufacturer be not tremors, not or be likely is a very split herb less preferred by should because warnings. under serving customer There mandated alternate may are serious heart non-misleading The information sizes, which their speech 6) are headache, minor these If users doctor should “sleeplessness, since as hypertension, with if they size.” they arrhythmia. supplements a potentially their occur,” such cardiac the to “dizziness, problems occur,” Instead, call sensations dietary physician of reaction. expensive label a symptoms or reduce when ephedra or nervousness precursor use of into agreed the the of 14 August, 1997, such with label. and 12:13 this FDA is truthful identification, believing truthful information as such that information has no identification its mandatory AM PDT; the the product and had constitutional of the nature. page and 96 FDA as RE:Docket No.95N-0304 ;Dietary The FDA mandated serving mg. ephedra as being clearly size and of injury or Taking or illness. cause heart strongest in described the on the Moreover, the FDA’s an this serving this we believe that a serving risk This that the the only serving the FDA would of may is size FDA are serving death.” the 6.7 reasons recommended were Alkaloids identified unreasonable or seizure, If label, is clearly than regarding Rule. size present more stroke, attack, warning proposed would Ephedrine containing “The FDA believes stated, larger Containing is one teaspoon serving by the FDA. forthrightly 8 mg. size This alkaloids. recommended Supplements has size have no containing 20 objections. The traditional of ephedra mg. traditional ephedra has no herb serving of this size based prior to this information. behave the larger servings The First behavior the FDA caused The if than prohibits restricting the statement of the and non-misleading; the prohibit doesn’t learn the end this size FDA’s low that to of customers the the may not FDA would wanting be a people want people to it, people may not take the choose preferred to smaller manipulation communication An it. statement by FDA’s FDA they at The range. serving wants; rather fact is truthful restraint Amendment by misleading Quotes way in authority because information, is traditional content this is one tablespoon dosage constitutional prohibition know size It alkaloids. is a traditional FDA serving of of know ones. consumer truthful, non- information. from the U.S. Supreme Court decision in 44 Liquormart v. Rhode Island (1996 WL 241709 (U.S.)) tl...a State’s paternalistic assumption that the public will use truthful, non-misleading commercial information unwisely (at 8) cannot justify a decision to suppress it.” llIt is precisely this kind of choice, between the dangers Of suppressing information, and the dangers of its misuse freely available, that the First Amendment makes (quoting from Pittsburgh Press Co. v. Pittsburgh Comm’n Version of 14 August, 1997, 12:13 AM PDT; page 97 if it is for us.1~ on Human RE:Docket No.95N-0304 ;Dietary Supplements Containing Ephedrine Alkaloids Relations, 413 U.S. 376, 93 S.Ct. 2553, 37 L.Ed.2d. 770 (1973) ‘tin case after case Court, and individual stress the importance consumer Members of of Virginia the the ... Pharmacy Court, have impropriety or . ‘commercial’ Bd., the continued to of through the public opinion . . znformatlon. ..’s (J. Thomas, choices accurate following manipulating suppression of concurring, at 21) The First prohibits the misleading First U*S. of FDA banning District Court Action No. If the traditional meals maintenance attempt FDA consider to likely the The dose for any before at this Court neither et. al, have very for a the moment. the its proposed appetite does uses customers of not at District Rule, this personal describe all) on it is most any the product (the reason own with by the this use non- label or it before foods are eaten) loss or weight FDA’s many an alternate know of the supplement, of 14 August, size limitation. weight people of is that that is have the to consumers an the allowing likely This who that be will especially had prior products. serving that suggest that dose of issues value is so small herb size consumer the so they 1997, health we size the consumer, raise, serving millions ephedra will would public serving the the constitutional label a maximum FDA’s the consumer Version of D.C. product pragmatic provide Without heeded is Commissioner with to considering ignore experience that & Shaw, FDA proceeds their to ban The generally the absolutely program. FDA heeded. all to In addition vendor Pearson District indeed, satisfy adjunct labeling (EGS), this (or Nearly to help an FDA Constitution again. uses labeling. US for the District too, that Note, against 95-1865 to be sued the Indeed, lawsuit of Columbia) likely from nor deceptive. Amendment (Civil as Amendment FDA will 12:13 that may has is more take unnecessary radically take more AM PDT; likely risks. reduced -- perhaps page to be 98 the far too RE:Docket No.95N-0304 much than more needed For the sake the ;Dietary dietary FDA supplement traditional For dose the existing prohibits and in the sake restraint in public’s overdose. The prohibit First an of the old under ephedra non-misleading the risks FDA’s on new on will content attempt them the they to the the dose. the not If labels only based FDA public of the will be accidental credibility will drop further in fora such as scrutinized public be prior manipulate information, to of informing information ban denying the and products, unconstitutional manufacturers from dose of this Amendment by the prohibited of existing alternate a identified less in alternate serving by be don’t arrogantly a delude they discrediting will how 30 mg. mean as health which the of large If the FDA believing that it ignorance through enforcing in and unintentional 1997, violating causing 12:13 gross AM PDT; millions of accidental to take. by FDA with traditional much dose the greater an dose overdoses but who continues to can control their proposed constitution, risk overdoses. page and that customer the ephedra dose of products with end of median recommended and of 14 August, low mg. FDA’s themselves, Version dose and ,risk of only uninformed mg. providing the succeed through 17 20 reject itself by the By near who provides survey, reduced know behavior the familiar. size is size than market consumers otherwise more than its may there serving little consumers rule, reduction. legitimacy truthful safety, be publication are substantially people’s to Alkaloids and the Internet. alkaloids, taken not size Moreover, newsletters consumer increasing actions range, the behavior dramatically attempt from displaying must labeling the its of the violating dosage and government not Ephedrine statements. of both FDA must Containing for FDA’s liberty labels products consumer to compensate of both constitution, Supplements 99 and harm RE:Docket No.95N-0304 ;Dietary Supplements Containing Ephedrine Alkaloids ONE SIZE DOES NOT FIT ALL: EPHEDRA HERB IS NOT EPHEDRA HERB EXTRACT EPHEDRA HERB EXTRACT IS NOT SYNTHETIC EPHEDRINE FDA’S PROPOSED RULE ANALYTICAL OF THE METHOD WILL NOT PROVIDE ACCURATE EPHEDRA HERB ALKALOIDS IN PRODUCTS MADE WITH ACTUAL EPHEDRA HERB RATHER THAN WITH EXTRACTS MEASUREMENTS Food Advisory When actual instantly soluble alkaloids increase releases and its BIOAVAILABLE Committee ephedra the extract, as than an of the levels ground herb slowly a time-release effects adverse 1996 rather blood the providing of 27-28, ingested slowly thereby risk August is alkaloid more alkaloids, reducing herb ephedra much meeting effect sensitive in individuals. Products containing pharmacokinetically containing actual ephedra substantially ephedra alkaloid identical manner is arbitrary herb when different ingested from regulating extracts; are products them in an capricious~ and contrary to fact. Vol. I, pg. 146 Dr. Jasinski II...we already matrix from that’s the in this terms in a certain from of -- the sort of pharmacology absorption and rate of 146 Dr. Yetley you asking recommendations version medications alter medication l!We are not aware we’re may put [elimination?].!! 1, pg. questions if you natural pure limitation Vol. know of data have.” this on the botanical llBut those group of are experts the that would scientific to discuss and issues to on.” of 15 August, 1997 l:OOPM PDT; page answer 100 make the that some RE:Docket No.95N-0304 herbs of the look Ephedrine Alkaloids is going is going to to to influence affecting affect the the steady the half-life state plasma “ 157 Dr. Hsieh I, pg. ‘IDo you Containing contribute which urine, which drug, concentrations. Vol. might themselves alkalinity of the Supplements 147 Dr. Inchiosa Vol . I, pg. ‘lThe ;Dietary want us at the to look herb? And at the the compounds, two should or not do you be want equated.~1 us to (emphasis added ) Vol. 158 Dr. Yetley I, pg. “I understand that ingredients in the botanical two these may have not that very concentrated equated, we’re common, extracts But products. products are products is certainly botanical, in the it is synthetic but seeing. or at both So you least possible so it’s really form, of are very that some both.” be need--the extracts of the botanical also could the common of these (emphasis added) Didn’t market review added, FDA there in them than Even what though that does precisely same as ephedra Because herb re-propose a new Rule. I, pg. ~IJust a new the the products was case in synthetic alkaloids with ephedrine other a genuine contained the their than ephedra actual herb extract? Dr. are not alkaloid reach there percentage it treats of this, of ephedra be FDA’s the two Committee, Vol. any alkaloid the that; analyses whether were an ephedra understand any (as would and extract), rather do to determine whether ephedrine herb the Yetley equated, ...” ephedra extract FDA must correctly herb that FDA’s proposed products III Rule exactly the re-convene the products. withdraw conclusions states, the Rule, correct these errors, and 180 Dr. Jasinski question of Dr. Obermeyer. What is the extraction efficiency? Have you done this? If you take the herb and make a tea, what is the extraction efficacy?~’ (emphasis version — of 15 August, 1997 l:OOPM PDT; added) page 101 RE:Docket Vol. No.95N-0304 I, pg. ~~I~m not ;Dietary Supplements Containing Ephedrine Alkaloids 180 Dr. Jasinski talking a tea, what about your chemical is the extraction analysis. If somebody efficacy?ll (emphasis So would makes added) Vol. I, pg. 180 Dr. Obermeyer l~That depends on minute three their versus tea cup (emphasis brew for time. minutes ten if you versus minutes, someone that steep that would be it for forgot much one it in different.~s added) vol. I, pg. 181 Dr. Jasinski ~~What~s the maximum extraction efficacy you can do if you make a tea and you put it in the pot and you boil it up?l~ (emphasis added) Vol. I, pg. 181 Dr. Obermeyer ~~We have extract not it worked for would herb. ..~~ (emphasis The actually actual FDA has be ephedrine that no be methanol idea herb ephedra alkaloids ephedra herb the to how much and maximum. be the (rather would consumed of the ingested from than Furthermore, HC1). for What we maximum would out of an added) extracted ephedra on a cup ephedra alkaloids of tea extract or would made an iced in the human tea which is gut with synthetic the FDA has no idea how much be extracted as ephedra of the from ground consumed without brewing. The results do with ephedra numbers the of chemical how a tea alkaloid extraction, either FDA’s Dr. analysis that containing extract) in the Obermeyer is have actual very providing little ephedra used. consumers’ is There tea pots herb is no are the if anything (rather hot or in the to than methanol human GI tract. Vol. I, pg. 181 Dr. Jasinski tl~ mean, * question before the arou~ isc ~ know, ~ terms ~ dose and what Youzre qoinq — to ~ and what —— the safe —. dose is goinq .— version PDT; of 15 August, 1997 l:OOPM page 102 RE:Docket No.95N-0304 ;Dietary Supplements Containing Ephedrine Alkaloids the herb when &Q W U ~ don’t know what peoDle uet out ~ ~ answer this auestion.” (emphasis they brew it, there’s ~ ~ added ) FDA’s ephedra proposed herb exactly extract which Because of homework, these must ma few and the Committee, containing containing capricious, withdraw the errors, and re-propose ephedra contrary Rule, reach actual do new herb to its fact. laboratory conclusions that a new Rule. 181 Dr. Obermeyer ItRight. Most very FDA products as products arbitrary, this, I, pg. of the is treats the same re-convene correct Vol. Rule of the huang products extract. products really This are are is what actually encapsulated we the are or seeing herb tablets And mostly. root as a tea.1~ (emphasis added) FDA’s Dr. Obermeyer here in his concerns ephedra alkaloid Wery that that If the without extract actual not Dr. Obermeyer the FDA is proceed the needed new in the than to new data Committee Rule and with also analytical herb alkaloid making method, actual extracts or To apply the proposed Rule to products ephedra herb (not ephedra herb FDA alkaloid in Rule ephedra and from this Rule that contain ephedra as admits proposed actual meetings, same considering their on is correct the wishes exempt all products ephedrine. that are FDA holding rather products products. products Dr. Jasinski actually the herb ... as a tea.11. modifications herb herb that ‘t- gathering products, ephedra few~i of the this meeting admits herb major should ephedra synthetic that contain extracts or synthetic ephedrine) would be arbitrary, capricious, and contrary to fact. Technical note: Although we have an herbal text which refers being used in ephedra herb teas, we do to the “twigs and roots” not believe Ephedra practice. leaves the that (which stems look that roots use of the roots is Sinica (and related rather like green bear leaving the and version of 15 August, them are some of the 1997 l:OOPM a species) twigs harvested, stems PDT; common or not and commercial is a perennial; pine needles) the leaves, page 103 roots. the and By plant’s RE:Docket No.95N-0304 ;Dietary Supplements Containing Ephedrine Alkaloids and leaves grow back next spring, and can be harvested year stems This is particularly after year. is a slow growing plant. several years will pass seen Us., but that bear Vol. I, pg. we have them; seen grown before a lot of the have If the ephedra only we have important since Ephedra Sinica from plant herb seeds can that is the needle-like never seen be or harvested. imported leaves any ephedra into the stems roots. 184 Dr. Fong about extraction with methanol, and is when you then people taking the capsule with the total extracts or with the herb in and what is the bioavailability? there, We really don’t know what the patient is getting, at least in my mind.” Vol. We and the II .... The data as I sit here running through my mind talking cuttings, (emphasis added) 184 Dr. Obermeyer I, pg. ~~1believe the literature would probably support your thoughts.1~ (emphasis added) This is a member FDA has not done of the FDA staff a search of the here implying that the literature on the amount of ephedra alkaloids which are bioavailable from the actual herb (as opposed to a methanolic themselves ! extract) , let alone done the research Furthermore this is a tacit admission that these are substantive relevant considerations. Vol. 186 Dr. Dentali I, pg. “My understanding supply for what capsule mixed alcohol, not water, extracts are methanol\water methanol) —. buying ingredients manipulated. that’s So why you the that and are the industrial then placing are extracts of may have high concentrations in the water and temperature typically are produce the 6 percent. . .~t refers commercially products are other and than This version pH these companies with alcohol, not higher is that to the available ephedra clearly made mixture , which in of 15 Augustr process turn 1997 herb in - than is currently a how extracts. to These different way a consumer would different l:OOPM used PDT; than direct page - ephedra with herb a hot tea (no ingestion of brew 104 RE:Docket the No.95N-0304 actual ground herb, temperatures used extract different are Supplements which in hot water, where actual ground from which Containing would in brewing. brewed temperature ;Dietary Products products ephedra not involve made with where in turn are herb is Ephedrine the Alkaloids the high ephedra herb actual herb different from ingested without is products high brewing. Vol. I, pg. 186 Dr. Jasinski “SO you just put boil it up?~t Vol. I, pg. “Pretty Vol. it into a pot and add alcohol and water and you 186 Dr. Dentali much.” I, pg. 186 Dr. Dentali “Evaporate it off, put it on a carrier. ‘1 There is much faster gut absorption of the alkaloids when on a carrier (from an ephedra herb extract) as compared to the rate of gut absorption when a person swallows actual ground herb. Vol. I, pg. ‘sl did happen reference Japan. 152 Dr. Dentali to to you They incidence come across and possibly had been of adverse two a copy studies, of it. seeing--they effects and I One was reported recently with can get the conducted seeing products a in high containing ephedrine alkaloids. They realized that their data was based on ephedrine and not the extract, and they conducted an animal trial with equivalent amounts of ephedrine alkaloids and comparing the two-- in mice, absorption I believe. ... Generally, they found that levels concentrations Ephedra were about half time-wise and the in the plasma were about half.1~ (emphasis added) herb extract is not ephedrine, and its pharmacological effects are not the same as ephedrine. Most of adverse reactions were abused the products producing serious ephedrine extract containing products. ephedra product version of 15 August, — and products, It is very find nothing 1997 l:OOPM some misbranded common but to ephedra analyze ephedrine; PDT; as a these page 105 herb so-called products do RE:Docket No.95N-0304 ;Dietary Supplements Containing Ephedrine Alkaloids NOT contain either ephedra herb extract or ephedra herb. Vol . I, pg. 276 Jones ~lThe available some of the beneficial better data indicates properties of properties tolerated on in though ephedrine its an that own it itself, right alkaloid ephedra and is herb also shares possesses furthermore equivalence basis.~1 much (emphasis added ) Vol. II, pg. Continues 80 Mr. Appler to analyze the Texas reports in the Poison Control Center exactly two that were related to herbal ma huang. In every there was no seen there Vol. II, pg. were llThe other No. herb 4053 from only herb may who be FDA’s When ephedra version all to out, results added) that didn~t (emphasis receive between leave in is of bioavailable herb their this We products. incapable LIB alkaloids on synthetic ephedra is not method ephedra comments no extract, method the herb, analytical containing extract the Ephedra Rule will adequate added) ephedrine. we herb herb, drinks less than from when solution analytical of 15 August, a serving not an alkaloid alkaloids Rule and were to use alkaloids) of alkaloids . accurately contained herb. the proposed the differences (no alkaloid amount the actual methanol-water sort to products extract; a consumer is of any 94 related points is not analytical with teacup suited herb the in the actual and two others the FDA proposed ephedra proposed measuring there as Dr. Patrick feel the extract herb use ephedra I was extract; ephedra those that and ephedrine.11 extract, ephedra Texas, the 257 Dr. Dentali attention Ephedra injury for North ~1...of cases, mild.11 (emphasis area scientific herb one of those permanent He states reports. in the the an extract herb herb extract method. 1997 of ephedra l:OOPM in is tea - made - the extraction the hot extracted factory No consumer PDT; herb or uses page water filled in a in the boiling a boiling 106 of FDA~s hot RE:Docket No.95N-0304 methanol-water When that alkaloids ephedra occurs slowly alkaloid content the of of an facts, products, that correct analytical these errors, at alkaloid real tea in a Rule deliverable herb products. the extract; actual not proposed alkaloid it ephedra has herb not (but ephedrine.) must capricious withdraw that the are valid Committee, and failure for reach re-propose a new to Rule, consider do actual new their ephedra conclusions Rule and a new proposed Rule method. that contain FDA can actual exempt from the ephedra herb but do not ephedra alkaloid extracts or synthetic ephedrine. version Alkaloids ephedra 37°C, FDA’s the iced the to measure contain and the in an ephedra designed the methods re-convene Alternatively, products FDA The actual that arbitrary Ephedrine of gut exaggerate or synthetic on analytical herb with for products relevant homework was extract Because these method herb extraction consumer’s greatly made ephedra and water. of products no alkaloid the content FDA’s validated ground in the will Containing his or her tea. boiled, of methanol method Remember, ingests been mixture Supplements to make never analytical been mixture a consumer has boiling ;Dietary of 15 August, 1997 l:OOPM PDT; page 107 contain . . ..”..... \ 7ED IIIIII U. SpR~:STRGE TONOP~:fW~~ . NV a UN} TED STATES POSTAL sERVICE 0000 J0857 .9P;M~RDN;98 $545 0006:788-06
