Summary
Synopsis: Fenfluramine2 has been used for a number of years as a short-term adjunct to diet in the management of obesity. Controlled studies and clinical experience have shown that it possesses anorectic activity at least as good as that of other therapeutically useful drugs of its type, but like these drugs it has only a limited role in the overall management of obesity. Tolerance to the anorectic effects of fenfluramine may possibly develop more slowly than to other chemically related drugs in patients with refractory obesity. The mechanism of its anorectic action is probably by an effect on the appetite control centres in the hypothalamus, rather than by an effect on glucose and lipid metabolism. However, its effect in enhancing glucose uptake into skeletal muscle may be of advantage in diabetes mellitus, preliminary studies suggesting that it is of potential use in maturity-onset obese diabetics who cannot be adequately controlled by dietary measures alone.
The starting dosage in obesity of 40mg daily should be increased gradually over 2 to 4 weeks to 60 to 120mg. In general, little extra benefit is gained by higher dosage. When a course of therapy is to be discontinued, fenfluramine dosage should be reduced gradually over a period of 2 to 4 weeks in order to avoid mood depression which has occurred in some patients on abrupt withdrawal of the drug. With these recommendations, the majority of patients tolerate fenfluramine satisfactorily, although some patients may have to discontinue the drug because of troublesome gastro-intestinal problems, diarrhoea, drowsiness or dizziness. Unlike other amphetamine-derived anorectics, fenfluramine is not a central stimulant in therapeutic doses, and it probably has little abuse potential.
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Manuscript reviewed by: G.E. Bacon, Professor of Pediatrics, Department of Pediatrics and Communicable Diseases, University of Michigan Medical Center, Ann Arbor, Michigan, USA; E.O. Balasse, Associate Professor of Medicine, Laboratoire de Médecine Experimentale, Université Libre de Bruxelles, Bruxelles, Belgium; W.J.H. Butterfield, Vice-Chancellor, University of Nottingham, University Park, Nottingham, England; E. Costa, Chief, Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Washington, DC, USA; J.M. Court, Department of Paediatrics, Royal Children’s Hospital, Melbourne, Australia; D. Craddock, South Croydon, England; S. Garattini, Director, Instituto di Richerche Farmacologicha ‘Mario Negri’, Milano, Italy; R.B. Goldrick, Department of Clinical Science, Australian National University, Canberra, Australia; W.P.U. Jackson, Department of Medicine, University of Cape Town, Observatory, Cape, South Africa; N.A. Kaufmann, Associate Professor of Nutrition, Hadassah Medical School, Hebrew University, Jerusalem, Israel; J.F. Munro, Medical Unit, Eastern General Hospital, Edinburgh, Scotland; R.E. Noble, Department of Medicine, University of California, San Francisco Medical Centre, San Francisco, USA; J. Offermeier, Head, Department of Pharmacology, Potchefstroom University, Potchefstroom, South Africa; I. Oswald, University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, Scotland; I. Persson, Chief Physician, Medical Department E, Frederiksberg Hospital, Copenhagen, Denmark; B. Potgeiter, Department of Pharmacology, Potchefstroom University, Potchefstroom, South Africa; N. Sapeika, Emeritus Professor of Pharmacology, Department of Pharmacology, University of Cape Town, Observatory, Cape, South Africa; T. Silverstone, Consultant Psychiatrist, German Hospital, London, England; F.O. Simpson, Professor of Medicine, Wellcome Medical Research Institute, University of Otago Medical School, Dunedin, New Zealand; Judith M. Steel, Diabetic and Dietetic Department, The Royal Infirmary, Edinburgh, Scotland.
See subject index in each issue for further indexing terms.
‘Grazilan’, ‘Minifage’, ‘Miniphage’, ‘Ponderax’, Ponderal’, ‘Ponflural’ (Servier); ‘Pondimin’ (Robins).
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Finder, R.M., Brogden, R.N., Sawyer, P.R. et al. Fenfluramine. Drugs 10, 241–323 (1975). https://doi.org/10.2165/00003495-197510040-00001
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DOI: https://doi.org/10.2165/00003495-197510040-00001