A close look at fenfluramine and dexfenfluramine

Journal of Emergency Medicine

Volumn 16, Issue 2, 1998, Pages 197-205

  Vivero, Lisa E ^a   Anderson, Philip O ^a   Clark, Richard F ^b  

^a UCSD MEDICAL CENTER   (United States)

^b California Poison Contr Syst S D ^*  (United States)

Author keywords

Anorectic; Anorexiant; d,l fenfluramine; Dexfenfluramine; Fenfluramine

Indexed keywords

AMINOREX; AMPHETAMINE; ANOREXIGENIC AGENT; ANTIDEPRESSANT AGENT; ANTIMIGRAINE AGENT; DEXFENFLURAMINE; FENFLURAMINE; FLUOXETINE; METHAMPHETAMINE; MONOAMINE OXIDASE INHIBITOR; PHENTERMINE; PHENTERMINE RESIN; PLACEBO; SEROTONIN; SEROTONIN UPTAKE INHIBITOR;

CLINICAL TRIAL; COMA; CONVULSION; DEPRESSION; DIET RESTRICTION; EXERCISE; FOOD AND DRUG ADMINISTRATION; HUMAN; OBESITY; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; SEROTONIN BLOOD LEVEL; SEROTONIN SYNDROME; VALVULAR HEART DISEASE; WEIGHT REDUCTION; WITHDRAWAL SYNDROME;

EID: 0032033141     PISSN: 07364679     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0736-4679(97)00289-8     Document Type: Article

References (74)

1. 1. Pi-Sunyer FX. Medical hazards of Obesity. Ann Intern Med. 1993;119:655-60.
2. 2. Manson JE, Willett WC, Stampfer MJ, et al. Body weight and mortality among women. N Engl J Med. 1995;333:677-85.
3. 3. Kuczmarski RJ, Flegal KM, Campbell SM, Johnson CL. Increasing prevalence of overweight among US adults: the national health and nutrition examination surveys. 1960 to 1991. J Am Med Assoc. 1994;272:205-11.
4. 4. Stunkard A. Overweight Americans weigh in as the majority. The San Diego Union-Tribune. 1996: Oct 16.
5. 5. Interneuron Redux phase IV advisory committee review. Washington, DC: F-D-C Reports. Inc., The Pink Sheet. 1996;58:T&G-2.
6. 6. Wyeth/interneuron redux posts $116.7 mil. In sales through November. Washington, DC: F-D-C Reports. Inc., The Pink Sheet. 1997;59:14.
7. 7. Elliott BW. A collaborative investigation of fenfluramine: anorexigenic with sedative properties. Curr Ther Res. 1970;12:502-15.
8. 8. Weintraub M, Sundaresan PR, Madan M, et al. Long-term weight control Study 1 (weeks 0 to 34). The enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. Clin Pharmacol Ther. 1992;51:586-94.
9. 9. Weintraub M, Sundaresan PR, Schuster B, et al. Long-term weight control study II (weeks 34 to 104). An open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise. Clin Phamacol Ther. 1992;51:595-601.
10. 10. Weintraub M, Sundaresan PR, Schuster B, Mosucci M, Stein EC. Long-term weight control study III (weeks 104 to 156). An open-label study of dose adjustment of fenfluramine and phentermine. Clin Pharmacol Ther. 1992;51:602-7.
11. 11. Weintraub M, Sundaresan PR, Schuster B, et al. Long-term weigh control study IV (week 156 to 190). The second double-blind phase. Clin Pharmacol Ther. 1992;51:608-14.
12. 12. Weintraub M, Sundaresan PR, Schuster B, Averbuch M, Stein EC, Byrne L. Long-term weight control study V (weeks 190 to 210). Follow-up of participants after cessation of medication. Clin Pharmacol Ther. 1992;51:615-8.
13. 13. Weintraub M, Sundaresan PR, Cox C. Long-term weight control study VI. Individual participant response patterns. Clin Pharmacol Ther. 1992;51:619-33.
14. 14. Weintraub M, Sundaresan PR, Schuster B. Long-term weight control study VII (weeks 0 to 210). Serum lipid changes. Clin Pharmacol Ther. 1992;51:634-41.
15. 15. Garattini S. Central mechanisms of fenfluramine and related anorectic drugs. Jpn J Pharmacol. 1981:31(suppl):29P-35P.
16. 16. Anonymous. Dexfenfluramine for obesity. Med Lett Drugs Ther. 1996;38:64-5.
17. 17. Wurtman JJ, Wurtman RJ, Growdon JH, Henry P, Lipscomb A, Zeisel S. Carbohydrate craving in obese people: suppression by treatments affecting serotonergic transmission. Int J Eat Disord. 1981;1:2-15.
18. 18. O'Connor HT, Richman RM, Steinbeck KS, Caterson ID. Dexfenfluramine treatment of obesity: a double blind trial with post trial follow up. Int J Obes. 1995;19:181-9.
19. 19. Pawan GLS. Effect of fenfluramine on blood-lipids in man. Lancet. 1969;1:498-500.
20. 20. Invernizzi R, Bertorelli R, Consolo S, Garattini S, Samanin R. Effects of the I isomer of fenfluramine on dopamine mechanisms in rat brain: further studies. Eur J Pharmacol. 1989;164:241-8.
21. 21. Saletu B, Barbanoj MJ, Anderer P, Sieghart W, Grunberger J. Clinical-pharmacological study with the two isomers (d-,l-) or fenfluramine and its comparison with chlorpromazine and d-amphetamine: blood levels, EEG mapping and safety evaluation. Methods Find Exp Clin Pharmacol. 1993;15:291-312.
22. 22. Le Douarec JC, Schmitt H, Laubie M. Etude pharmacologique de la fenfluramine et de ses isomeres optiques. Arch Int Pharmacodyn Ther. 1966;161:206-32.
23. 23. Finer N, Craddock D, Lavielle R, Keen H. Dextrofenfluramine in the treatment of refractory obesity. Curr Ther Res. 1985;38:847-54.
24. 24. Garattini S. Similitudes et differences entre la fenfluramine et l'amphetamine. La Vie Medicale au Canada Francais. 1973;2: 318-24.
25. 25. Franko BV, Honkomp LJ, Ward JW. Cardiovascular and autonomic effects of fenfluramine hydrochloride. J Pharm Pharmacol. 1965;17:222-6.
26. 26. Fink M, Shapiro DM, Itil TM. EEG profiles of fenfluramine, amobarbital and dextroamphetamine in normal volunteers. Psychopharmacologia. 1971;22:369-83.
27. 27. Colmore JP, Moore JD. Fenfluramine, an amphetamine-like appetite suppressant with paradoxical central nervous system and cardiovascular effects (Abstract). J New Drugs. 1966;6:123.
28. 28. Freedom of information approval package for fenfluramine. Washington, DC: U.S. Food and Drug Administration; Oct. 16, 1996.
29. 29. Foxwell M, Funderburk WH, Ward JW. Studies on the site of action of a new anorectic agent, fenfluramine. J Pharmacol Exp Ther 1969;165:60.
30. 30. Garattini S, Caccia S, Mennini T, Samanin R, Consolo S, Ladinsky H. Biochemical pharmacology of the anorectic drug fenfluramine: a review. Curr Med Res Opin. 1979;6:15-27.
31. 31. Dexfenfluramine package insert. Philadelphia, PA: Wyeth Laboratories Inc. 1996 April.
32. 32. Wyelh-Ayerst fenfluramine "Dear Doctor" letter warns against "Fen/Phen". Washington, DC: F-D-C Reports, Inc., The Pink Sheet. 1997;59(9):T&G 2.
33. 33. Fenfluramine package insert. Richmond, VA: A.H. Robins, Inc. 1996 June.
34. 34. Waal-Manning HJ, Simpson FO. Fenfluramine in obese patients on various antihypertensive drugs. Lancet. 1969;2:1392-5.
35. 35. Finer N, Craddock D, Lavielle R, Keen H. Effect of 6 months therapy with dexfenfluramine in obese patients: studies in the United Kingdom. Clin Neuropharmacol. 1988;11:S179-86.
36. 36. Noble RE. A six-month study of the effects of dexfenfluramine on partially successful dieters. Curr Ther Res. 1990;47:612-19.
37. 37. Guy-Grand B, Apfelbaum M, Crepaldi G et al. International trial of long-term dextenfluramine in obesity. Lancet. 1989;2:1142-4.
38. 38. Mathus-Vliegen EMH, Van De Voorede K, Kok AME, Res AMA. Dexfenfluramine in the treatment of severe obesity: a placebo-controlled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behavior. J Intern Med. 1992;232:119-27.
39. 39. Weintraub M, Hasday JD, Mushlin AI, Lock wood DH. A double-blind clinical trial in weight control, use of fenfluramine and phentermine alone and in combination. Arch Intern Med, 1984; 144:1143-8.
40. 40. Steele JM, Briggs M. Withdrawal depression in obese patients after fenfluramine treatment. Br Med J. 1972;3:26-7.
41. 41. Stunkard A, Rickels K, Hesbacher P. Fenfluramine in the treatment of obesity. Lancet. 1973;1:503-5.
42. 42. Steel JM, Munro JF, Duncan LJ. A comparative trial of different regimens of fenfluramine and phentermine in obesity. Practitioner. 1973;211:232-6.
43. 43. Gurtner HP. Aminorex and pulmonary hypertension. A review. Cor et Vasa. 1985;27:160-71.
44. 44. Miczoch J, Probst P, Szeless S, Kaindl F. Primary pulmonary hypertension: follow-up of patients with and without anorectic drug intake. Cor et Vasa. 1980;4:251-7.
45. 45. Cameron J, Waugh L, Loadsman T, White P, Radford DJ. Possible association of pulmonary hypertension with an anorectic drug. Med J Aust 1984;140:595-7.
46. 46. Heuer HL, Benoit W, Heydrich D. Pulmonale hypertonie durch appetitzugler (Mirapront). Chir Praxis. 1978;23:497-505.
47. 47. Freedom of information approval package for dexfenfluramine. Washington, DC: U.S. Food and Drug Administration. Dec. 4, 1996.
48. 48. Malmquist J, Trell E, Torp A, Lindstrom C. A case of drug-induced (?) pulmonary hypertension. Acta Med Scand. 1970;188: 265-72.
49. 49. Abenhaim L, Moride Y, Bremit F. et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med. 1996;335:609-16.
50. 50. Thomas SHL, Butt AY, Corris PA, et al. Appetite suppressants and primary pulmonary hypertension in the United Kingdom. Br Heart J. 1995;74:660-3.
51. 51. Herve P, Launay JM, Scrobohaci ML, et al. Increased plasma serotonin in primary pulmonary hypertension. Am J Med. 1995; 99:249-54.
52. 52. Brenot F, Herve P, Petitpretz P, Parent F, Duroux P, Simonneau G. Primary pulmonary hypertension and fenfluramine use. Br Heart J. 1993;70:537-41.
53. 53. Hosoda Y. Pathology of pulmonary hypertension: a human and experimental study. Pathology Int. 1994;44:241-67.
54. 54. Michelakis ED, Archer SL, Huang JMC, Nelson DP, Weir EK, Anorexic agents inhibit potassium current in pulmonary artery muscle cells. Am J Respir Crit Care Med. 1995;151(suppl):A725.
55. 55. Atanassoff PG, Weiss B, Schmid ER, Tornic M. Pulmonary hypertension and dexfenfluramine. Lancet. 1992;339:436. Letter.
56. 56. Roche N, Labrune S, Braun JM, Huchon GJ. Pulmonary hypertension and dexfenfluramine Lancet. 1992;339:436-7. Letter.
57. 57. Abenhaim L. Rich S, Benichou J, Begaud B. Appetite-suppressant drugs and primary pulmonary hypertension. N Engl J Med. 1997; 336:512-3.
58. 58. Douglas JG, Munro JF, Kitchin AH, Muir AL. Proudfoot AT. Pulmonary hypertension and fenfluramine. Br Med J. 1981;283: 881-3.
59. 59. Loogen F, Worth H, Schwan G, Goeckenjan G, Losse B, Horstkotte D. Long-term follow-up of pulmonary hypertension in patients with and without anorectic drug intake. Cor et Vasa. 1985; 27:111-24.
60. 60. Gaul G, Blazek G. Deutsche E, Heeger H. Ein fall von chronischer pulmonar hypertonie nach fenfluramineinahme. Wien Klin Wochenschr. 1982;22:618-21.
61. 61. Graham DJ, Green L. Further cases of valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997; 337:635.
62. 62. Connolly HM, Crary JL, McGoon MD et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997; 337:581-8.
63. 63. Analysis of cardiac valvular dysfunction in patients treated with appetite suppressants. Washington, DC: U.S. Food and Drug Administration. September 1997.
64. 64. Gold RG, Gordon HE, Da Costa RWD, Porteous IB. Fenfluramine overdosage. Lancet. 1969;2:1306.
65. 65. Fleisher MR, Campbell DB. Fenfluramine overdosage. Lancet. 1969;2:1306-7.
66. 66. Veltri JC, Temple AR. Fenfluramine poisoning. J Pediatr. 1975; 87:119-21.
67. 67. LoVecchio F, Curry SC. Dexfenfluramine overdose. J Toxicol Clin Toxicol. 1997;35:492. Abstract.
68. 68. Campbell DB, Moore BWR. Fenfluramine overdosage. Lancet. 1969;2:1307.
69. 69. Darmady JM. Diazepam for fenfluramine intoxication. Arch Dis Child. 1974;49:328-30.
70. 70. Oswald I, Lewis SA, Dunleavy DLF, Brezinova V, Briggs M. Drugs of dependence though not of abuse: fenfluramine and imipramine. Br Med J. 1971;3:70-3.
71. 71. Lewis SA, Oswald I, Dunleavy DLF. Chronic fenfluramine administration: some cerebral effects. Br Med J. 1971;3:67-70.
72. 72. Woodward E Jr. Clinical experience with fenfluramine in the United States: amphetamines and related compounds. In: Costa E, Garrattini S, eds. Proceedings of the Mario Negri Institute for Pharmacological Research, New York: Raven Press; 1970:685-91.
73. 73. Hawks DV. Unusual effect of fenfluramine. Br Med J. 1970;1:238.
74. 74. DEA to continue to monitor fenfluramine abuse potential following descheduling. Washington. DC: F-D-C Reports, Inc., The Pink Sheet. 1997;59(19):T&G-1.