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EL E. A. T. Halt Ephedrine Abuse Today Kristopher ! R. Michal f., February 8, 1999 Founder/Director P.O. Box I I 03 g “c:: -, :: P.Q BP)( I;IQ3 Novi, Michigan 4S376- I 103 (248) 34 S-2598 [email protected] /9s3199s Barbara J. Michal . x.. 1972-1997 Rosanna C. Porras -- Dockets Management Branch (HFA-305) Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 Novi, Ml 4S376-1 103 (248) 34 S.259S Re: Henry Porras Katy Porras Docket No. 98N-0148 World Health Organization, Proposed Ephedrine Restrictions Directors 541 4th Street Fillmore, CA 93015 Ladies and Gentlemen: (805) 524-0443 My name is Barbara Michal. I am Chair of the Board of Directors of Halt Ephedrine Abuse Today (HEAT), a non-profit national coalition I founded after ephedrine caused the death of my 24 year old son, Kristopher, on March 14, 1997. A newspaper story regarding Kristopher’s death is appended at Tab A. I am writing to provide information in support of the WHO proposed restrictions on ephedrine manufacturing and distributing. THE FACTS ABOUT EPHEDRINE Addiction and Abuse - Anecdotal and Scientific Evidence Since Kristopher’s death, I have been researching this dangerous and addictive drug. Through my work with HEAT, I have been contacted by many ephedrine users and victims. As of February 7, 1999, of 111 contacts I have received, fifty-one percent (51 %) report addiction. Please look at that number closely -51%. A summary of the reports and the demographics of those who have contacted me are appended at Tab B. These anecdotal reports show addiction to and abuse of both herbal ephedrine products and chemical ephedrine products. Ephedrine has been identified as a drug of abuse for years. It is listed and discussed in the publication Drugs and Drug Abuse, 2nd Ed., Cox, Jacobs, LeBlanc, Marshman and Fehr, published in 1987. In July, 1995, the U.S. Food and Drug Administration published proposed rules concerning ephedrine in over-the-counter bronchodilator products.1 In those proposed rules, the FDA acknowledged that ephedrine carries a widespread potential for injury, addiction, abuse and misuse. P VP ~1~ Food and Drug Administration Docket No. 98N-0148 February 8, 1999 Page 2 In 1997, the National Institute of Health Sciences, in Tokyo, Japan conducted a study regarding hair analysis to detect drugs of abuse. Ephedrine was one of the drugs listed as a drug of abuse.2 In an analysis of drug use in sports, ephedrine was identified along with amphetamine and cocaine as stimulant drugs used and misused by athletes.3 Studies conducted in Texas have shown the addiction potential of ephedrine. Dr. Paul Wellman, Head of the Dept. of Psychology at Texas A & M University, with his colleagues, has published two studies showing that ephedrine has the same action as amphetamine and cocaine on dopamine in the brain.4 Diversion into Illegal Drug Manufacture Ephedrine is being diverted into the manufacture of two major illegal street drugs, methamphetamine and methcathinone. Because of this growing epidemic, the Methamphetamine Control Act was enacted in 1995 which banned single-ingredient ephedrine products and put restrictions for purchase and possession of ephedrine in place. However, the combination products (typically the “asthma aid” products which are combined with guaifenesin) are still being diverted. If all ephedrine products were reclassified as prescription only, a significant source of easy ephedrine supply for illegal drug manufacture would be eliminated. Adverse Reactions and Injuries - Anecdotal and Scientific Evidence I again refer you to the summary of contacts and demographic information at Tab B. These reports of adverse reactions and injuries are alarming in scope, and they represent the tip of the iceberg. In 1997, the FDA published an extensive report and proposed rules concerning ephedrine in dietary supplements.5 Under these proposed rules, ephedrine in dietary supplements would be limited to 8 mg. per dose, no more than 8 mg. per 6 hours, no more than 24 mg. per 24 hours, not to be used for more than 7 days. Additionally, it would prohibit claims for weight loss, body building, or energy enhancement, and would prohibit combining ephedrine with any source of caffeine. These proposed rules would also require significant warnings and contraindications in product labeling. There have also been scientific studies and reports of injuries and deaths from ephedrine. They identify strokeb, fatal ephedrine intoxication, coronary artery vasospasmg, dilated cardiomyopathy, acute myocardial infarctionl”, sudden deathl 1, psychosislz 13,acute hepatitis14 and kidney damage15 lb. The medical community has been warning repeatedly about the dangers of ephedrine. It’s time to heed the warning, CONCLUSION Ephedrine is a dangerous and addictive drug, in both its chemical and herbal forms. There is growing medical, anecdotal and scientific evidence of addiction, abuse, injuries and deaths. Additionally, ephedrine is being diverted into the manufacture of two major illegal street drugs, methamphetamine and methcathinone. Ephedrine has no place on the over-the-counter market, even Food and Drug Administration Docket No. 98N-0148 February8, 1999 Page 3 in combination products. The WHO proposed restrictions do not go far enough, i.e., making ephedrine available by prescription only no matter what kind of product contains it, but it is a step forward in the effort to regulate this terrible and destructive drug. I am grateful for the opportunity to share my information and opinions, and thank you for your consideration of my comments. Barbara J. Michal References 1. Federal Register, Vol. 60, No. 144:38643-47, July 27, 1995 2. Nakahara, Y; Kikura, R. Hair analysis for drugs of abuse. XIX. Determination of ephedrine and its homologs in rat hair and human hair. J Chromatogr B Biomed Sci Appl, 700:83-91, October 24, 1997 3. Clarkson, P; Thompson, H. Drugs and Sport - research findings and limitations. Sports Meal, 24(6): 366-384, December, 1997 4. Wellman, PJ; Miller, DK; Livermore, C L; Green, TA; McMahon, LR; Nation, JR. Effects of (-)-ephedrine on locomotion, feeding, and nucleus accumbens dopamine in rats. J. Psychopharmacology 135:133-140, 1998 Miller, DK; McMahon, LR; Green, TA; Nation, JR; Wellman, induces behavioral sensitization administration of ephedrine Psychopharmacology, Ms. No. 744, 1998 PJ. Repeated in rats. J. 5. Federal Register, Vol. 62, No. 107:30677-30724, June 4, 1997 6. Bruno, A; Nolte, KB; Chapin, J. Stroke associated with ephedrine use. Neurology, 43: 1313-16, 1993 7. Backer, R; Tautman, D; Lowry, S; Harvey, C; Poklis, A. Fatal ephedrine intoxication. J. Forensic Sci, 42(l): 157-9, January, 1997 8. Lustik, SJ; Chhibber, AK; van Vliet, M; Pomerantz, R.M. Ephedrine-induced coronary artery vasospasm in a patient with prior cocaine use. Anesth Analg, 84:931-3, April, 1997 . Food and Drug Administration Docket No. 98N-0148 February 8, 1999 Page 4 9. Gualtieri, J; Harris, C. Dilated cardiomyopathy in a heavy ephedrine abuser. J of Toxicology, Clinical Tox, 34:581-82, 1996 10. Cockings, JG; Brown, M. Ephedrine abuse causing acute myocardial infarction. Med J Aust, 167: 199-200, August, 1997 11. Theoharides, TC. Sudden death ofahealthy college stident related to ephedrine toxicity fromama huang-containing drink. JClin Psychopharmacol, 17(5):437-39, 0ctober,1997 12. Lake. CR; Tenglin, R; Chernow, B; Holloway, HC. Psychomotor stimulant-induced mania in a genetically predisposed patient; a review of the literature and report of a case. J. Clin Psychopharmacol, 3(2): 97-100, 1983 13. Roxanas, MG; Spalding, J. Ephedrine abuse psychosis. Med J Aust, 2: 639-640, November, 1977 14. Nadir, A; Agrawal, S; King, PD; Marshall, JB. Acute hepatitis associated with the use of a Chinese herbal product, ma-huang. Am J Gastroentrol, 91(7): 1436-8, July, 1996. 15. Powell, T; Hsu, FF; Turk, J; Hruska, K. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis, 32(l): 153-9, July, 1998 16. Blau, JJ. Nephrolithiasis associated with chronic ephedrine abuse. J Urol, 160(3 Pt. 1): 825, September, 1998 Mom wages war on ephedrine What to look for Woman blames over-the-counter asthma drug for her son’s death Ephedrine isn’t physically” ,addictive, but it can by physiologically addictive. That means people like the !@ they get from ephedrine a_@ take more. Soon, peoPle”@ taking larger and larger doses to get the same effect .:. because their bodies adjust to the amount they:re getting. By Nicole Bondi The Detroit News Barb Michal never thought the pep pills her q-year-old son picked up in the gas station would kill him. But they did, and Kris’ death has Michal working to let others know what she didn’t — that ephedrine is” a widely abused substance that can kill. “I knew he was taking it,” said Michal, of Novi. “He was using it so he wouldn’t sleep KI+S Michal as much. He was constantly pac”kinghimself with caffeine and this stuff.” On March 14, I@ Michal popped the small white pills for the last time. Official cause of death: ephedrine overdose. An autopsy showed no other drugs in his system. More than 900 injuries and 40 deaths related to ephedrine — also called Ma huang or herbal ecstasy — have been reported to the Food and Drug Administration, spokesman Arthur Whitmore said. Problems ., range from dizziness and tremors to heart attacks or strokes. “when I see it at convenience stores, I talk to the manager about getting it off the shelves; Michal said. So far, she has gotten three stores, including a Novi T-Eleven, to y;nk Mini Thin, the most popular brand. “Just from my own experience “There’s such a potential for abuse,” said Dr. Pamela ‘Gq; don, a cardiologist at the Detroit Medical. Center. i .,;. Ephedrine can cause bksod pressure to skyrocket or,~@. heart to beat faster. ‘ Substance abuse counselor Cheryl Abel surgests ~rents look out for the-se signs of ephedrine abuse ‘. . . ■ Hyperactivity E Lack of appetite 9 Secretiveness or withdrawal from the family ~ ■ Nausea or vomiting 9 Dizziness ■ Headaches WI@ you Can-cji under a<Food and Q~~ ~”” C[arence TabbJr./The Detd ,News Barb Mich-al, with her mmddaughter, ~~ica, 4Phew her sons mis, was t&ing ephed-tie but was una~ of the ~~e~. seeing people buy it, it makes me nervous,” said Rick Canzano, owner of the Novi Y-Eleven. ‘We don’t know what people are going to do with the product after we sell it.” Ephedrine, available over the counter, is a central nervous system stimulant used in diet pills “and food supplements. Medically, it’s used in decongestants and asthma medicines Please see EPHEDRINE, Page 6C Administration proposal, .: ephedrine products Would.not be able to claim weight-loss or body-building t%nefitiland doses would be limited to less than 8 milligrams e=h ?J 24 milligrams per day. MIm nin, for instance, contains 25 milligrams of ephedrine. To-cornment on the proposal, write to the Food and Drug Admf@ tration, Dockets Management Branch, 12410 Parklawn Dr., Rockville, Md. 208:7. Mark it for the “ephedrine docket.” If you know someone taking eph@rine and would !ike more information, contact Barb Michal at.PCl 8csx.l!03, Novh Mich. 4@376. ,.““’ .. EPHEDRINE Coutinited from Page lC tohelp people breathe easier. But it’s also touted by herbal experts as an appetite suppressant and energy booster. Widespread teen abuse of nicotine has prompted tighter controls to keep it out of their hands and many experts believe ephedrine deserves the same treatment. The FDA is hewing public comment through mid-December on a proposal that w-ouh.i restrict how ephedrine is marketed. Many states already have banned or restricted its sale. In Michigan possessing more than 10grams is a felony punishable by up to two years in jail or a $2,000 fiie. Ten grams would be equivalent m 400 Mini Thio tablets. After her son’s death, Michal made sure her 6year-old daughter, Courtney, and her friends knew about the substance and its danger. “Iithey \veren’t taking Mini Thins, they knew someone who was,” Michal said. The little pills ae especially big with teen-agers. “It’s readily amilable. It’s at gas stations, party storesv said Cheryl Abel, a student assistance coordinator for W~ed Lake’smiddle schools. ‘You’llsee almost eve~ single place has them.” It’s often sold in six-pill packets — which many kids fmd easy to slip into their pockets — and is set out alongside NO-DOZand other so-called pep pills. The pills frequently are packaged in bright-colored pouches, with bold, colorful lettering. Mini Thin comes in bright blue w~appings with hot pink accents. BDI Pharmaceuticals, the company that distributes it, recently changed the product name to Mini Two-Way Actio~ with similar packaging. BDI was contacted several times, but declined to comment on its products for this story. Mini Thin and Mti Two-Way Action both clearly note they’re designed for astb relief. “Ephedrine is being advertised as based on asthma medicine. The problem is they’re marketing it as a stimulant,” said David Katchman, a Birmingham lawyer who works with schools and conuPunity groups, tdkirtg to kids about substance abuse. “For someone who’s not old enough to buy alcohol, this is easy to obtain.” Beyond being sold in convenience stores, ephedrine is abundantly advertised in teen and women% magazines. ‘T.xplode with energy” reads one ad that offem z5-mgephedrine pills in batches of 100 or 500 through the mail. “Anything that makes claims like Mini ~in and these other products and are available right next to the candy at the locol party store, that’s going to spark Clarence Tab6Jr./ The petroit News Barb Michal blames Mini Two-Way Action and Mini Thin, both with ephedrine, for her son Kris’ death this year at ~[. :,; Notthe same as NO-DOZ Ephedrine may be shelved next to pep pills such as NO-DOZ and Vivarin, but they’re not in the same class. The active ingredient in NO-DOZ is caffeine. “So that’s no different from drinking two cups of coffee,” said Dr. Pamela Gordon, a Detroit Medical But caffeine of adventure kids “Caffeine’s society,” Center cardiologist. doesn’t have thetsame as ephedrine allure does among 1 kind of a staple of use m our said Richard Weiss ot Maple- grove’s Youth Treatment ephedrine connotation. Center. “You say or Mini Thin, there’s a different The connotation is more! ike you’re doing a drug.” their curiosity” Katchrnan said. Stephanie Carl, 18, of Woodhaven, fmt tried Mini Thin when she was 15.At the time, she was experimenting with every drug from cocaine to Ritalin. Ephedrine was just one more way to get abuzz ‘They were easy to get and they were cheap,”Cad said.‘They were acceptable legal and you ~idn’t have to be a certain age to buy them.” Carl used to take five to eight pills at a time. The recommended dose is one every four houm not to exceed six in q hours. “I didn’t care how much I took or anything,” she said. Carl stopped using drugs when she realized how bad her life had gotten. She went through a drug treatment program and has been sober for almost a year. Yet, adults often don’t see ephedrine as dangerous because it’sso widely available — and even sold in health food stores. ‘men you we herbaL what do you think? Oh it’s natural, it’s safe,” Michal said. She asked her son to stop many times, but never pushed it because she . didn’t know how harmful it could be. “It’sjust like I told him to stop smoking too much: she xiid. ‘Yeah alcohol can kill you if you abuse it. It’s going to take years and years to killyou Tobacco’s going to take years ami years to kill you. Ephedrine will drop you like that: she said, snapping her fmgem. Ephedrine affects the cardlovasculx system causing blood pressure to rise, blood vessels to constrict and the heart beat to quicken. “Sometimes it felt uncomfortable because your heart was beating really fast: Carl said. But she would thii, “Oh well it gives me a buz so that’s OK.” Ephedrine has only become an issue in the last couple of yearn. “It’s really taken ,otT’ said Richard i Weiss+resider$al therapist at the Maplegrove Youth Treatment Center. “Now it almost seems like a s@ple.”Alot of kids have had some experience with it.” : In April, Wal-M~”began restricting the sale of ephedrhe. Cash registeti are programed to”limit eac~i customer ,to I three to six pack&13+ The chain also stopped carrying ‘the Iarge me-count bottles. over-the-counter Even Usipg ephedrine for asthma relief — a real ~ medical purpose — could be harmful. i “If people were using it for asthma, ~ the asthma’s probably um;ontrolled or 1 not being properly assessed by a physi- ~ cian or pharmacist,’” said Franz Neubrecht, vice-president: of business, \ services for Phafiacy S~rvices Inc., part of the Michigan Pharmacists= I & I Association. Neubrecht said he would like to see\ ephedrine moti strictly regtilated, but I not necessarily banned. .. “.~ , ~ “Ephedrine’s been used in,deconges- ~ tants for a long time. ... It’sve;y valuable . in that regard” Neubrecht said’.“Ifit’s S@ ; useful, it would be a shame, to totd$,, withdraw it.” 0 NUMBER OF CONTACTS: 46 Male 65 Female Youngest Oldest 16 Years 47 years Breakdown by age: CONTACTS REPORTING ADDICTION/DEPENDENCE: Male Female February 7, 1999 111 16-20: 19 contacts 21-25: 35 contacts 26-30:31 contacts 31-35: 12 contacts 36-40: 4contacts 41-45: 5 contacts 46+: 1 contacts Unknown age: 4 contacts 57 (51%) 54 (49 %) 22 35 CONTACTS REPORTING DOSAGE RUN-UP: REPORTED ADVERSE REACTIONS: Rapid Heart Beat Nervousness/tremors Insomnia Headaches Irregular Heartbeat Stomach Upset Chest Pain Shortness of Breath Body Aches Paranoia Difficult Urination Hallucinations Blackouts Seizures 81 73 72 49 47 46 42 41 36 31 23 18 10 6 (73%) (66%) (65 %) (44 %) (42 %) (41%) (38%) (37%) (32%) (28%) (21%) (16%) ( 9%) (5%) USING CHEMICAL EPHEDRINE PRODUCTS: 38 Reporting Addiction: USING HERBAL EPHEDRINE PRODUCTS: 19 Reporting Addiction: 60 51 HALT Tabulation EPHEDRINE of Contacts ABUSE through TODAY February7, 1999 Pagelof 12 Page20f 12 a) WI m 2 Page40f 12 suicidal Other card. arrhyth after stopped feelings emotional migraine; instability panic product diet pills allergy pills Product ma huang ephedra Ultra disorder Diet Diet Fuel ma huang Pep; Diet ephedrine Ultra HCL Slim Citra Mini-Thins Ephedrine Fuel Starting Amount/day (1 tab = 25 reg.) Current or Ending White Plus Cross Metabolize Thermolift 1 pill (mg?) 2 pills (mg?) 1 pill (mg?) 2 pills (mg?) 9 pills (mg?) 30 mg. “varies” 6 pills (mg?) 1 tab 100-150 12 2 pills (mg?) 1 pill (mg?) 2 pills (mg?] 6 pills (mg?) 30 mg. “varies” 6 pills (mg?) 6 tabs 50 mg. months 3 years pills (mg?) mg. Amount/day (1 tab = 25 reg.) Length of Use 1 vear 2 years 3 years 2 years 3 years Page 5 of 12 Page60f 12 Page70f 12 Page80f 12 DATA 81 Age 12106168 Gender Male Marital Status Location 30 82 83 10102173 I I 1 1/10/72 25 Male Female .. !=?A 26 09/08/79 Female Marr!ed I I Married I ~ Single lowa ~ Geomia I Wnnsvlvania Single 85 19 09128172 86 26 04117165 Male Single 33 87 88 05121162 I \ 11107182 Female Female I I Married I ~ Married 36 90 89 18 Male I I Single 09120177 21 06102151 47 Female Female Single Married Connecticut New York Addicted/Dependent Rapid Heart Beat 81ackouts Difficult Urination Irregular Heartbeat Seizures Body Aches Nervousness/Tremors Paranoia Chest Pain Insomnia Hallucinations Headaches Stomach Uoset Shortness of Breath Other Cranky Stroke Exacerbated Pre-Existing Panic Disorder Product Efedrin Metabolift Mini-Thins Black Two Wav Diet Fuel Blue Ladies Metaboiife Up Your Cross Gas Thermadrene ephedra Ultimate Orancre Starting Amount/day (1 tab = 25 reg.) Current or Ending 5-10 tabs 1 3 doses (mg?) ~ 2-3 tabs 4-6 tabs 9 pills (mg?) 4-5 @ 50 4 pills (mg?) 500 mg. + 1 pill (mg?) 1 pill (mg?) 4 pills (mg?) 500 mg. + 2-3 1 pill (mg?) m9. 200 tabs 3 doses (mg?) 15 tabs 4 tabs 9 pills 2 years 2 years months 16@50mg. (mg?) pills (mg?) Amount/day (1 tab = 25 reg.) Length of Use I 12 years [ I months t 1 year 1 months 4 years 1 year 3 days Page 9 of 12 . 0 Page llof 12 n % m m r. UJ m e m N : a a e N * r= s w G al 2 s m 2 c s hi u ~ ~ c m w 3 . ~ ; W 2 m 5 E a : g ~ : > % Q e 4 > 2 c .-o % 5 ~ m $ ~ $ m * ~ ~ g ~ ~ k : $ g n .!? m ~ 2 ~ z Q 2 F 8 c 0 n c z ~ .– A .; ~ E Z i -0 h s m .Y ‘; ~ : .,.,.,.,..: ,.,.,.,.,, ,. ,,,,,.,,,,,.,j ~g ,,,:,.,, .:‘ :,:: ,, ,. ..,. ,.::,:.;:,’ ;:~. ,.. ...,. -c G .w m % G Lj g : w ~ ; = m : g c .— c ,-0 z al c al -b ? 5 .c k z g : > m ~ = g .& = N = % = : F g ~ F ~ >m cmw up ~gll : A G W=n kom ~E+ fJ<- c . 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Acceptance Cfed( Initi?ls No Deliiery Day Date ❑ AM flPM Time ❑ Employee S!gnaturs AM OPM Time ~ AM u Mo. ~-~ way “ 3 Sig@3r:~& Addres&e Or Agent 31 .“-- “-”--j$:L{+_ . ..= x kme :T4ease Print ❑ 3rd Day ~ ZndDay Int’1Alpha Country Code Day Employee signature Time Total Postage 8 Fees Emp(oyee Si9nature . . .. pM_ . ““”::: “:+~r- .- : # &-w U WAIVER OFSIGNATURE (bomestic0.$) Addftfowl nwrhifisehurium Iswiii * wiiver of s&tire ii K@&&I: m be made without obtaining signature of addre=e OFaddressee’s a9ent (If dellvw e@OY@ JU*S I WISrIddIVaY that article can be left ill secure location) snd I authodze that debx? employee’s signature cunstituies valid progf of I FROM: r (PLEASEPRINTI PHONE ( ~Z~- ‘ -.*_.. - ? -= – TO (PLEASEPRINTI PHONE ( ) r -1 1 Label . ..__ -.——– 11 -B July 1997 ‘-’2A