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CONTINUING EDUCATION CREDIT nal half-life ranges from six to nine days, but it is significantly longer, about 16 days, in the obese.13 Rimonabant’s effectiveness in treating overweight or obese patients was studied during a program consisting of four randomlized, controlled trials, known as The Rimonabant in Obesity (RIO) program. Each trial (RIO-Europe, RIO-Lipids, RIO-North America, and RIO-Diabetes) compared rimonabant 5 and 20 mg/day with placebo. In these trials, rimonabant was as effective as sibutramine and orlistat.13 Rimonabant was approved in the United Kingdom as Acomplia in 2006. In the summer of 2007, however, the FDA voted against the sale of rimonabant in the U.S., under the brand name Zimulti, because of the medication’s psychiatric side effects. In October 2008, Sanofi-Aventis withdrew rimonabant from European markets because of safety concerns. In reviewing postmarketing data, the European Union found that rimonabant doubled the risk of psychiatric disorders in obese or overweight patients taking the drug. Taranabant. Although the FDA did not approve rimonabant, a drug with a similar mechanism of action—taranabant, a CB-1 receptor inverse agonist—was studied in phase 3 trials. Merck had expected to file for FDA approval; in October 2008, however, the company canceled further investigation into this experimental obesity drug. At more effective dosages, side effects increased excessively.14 Merck had been aiming for a 5% weight loss, but that goal was achieved only at the highest dose (4 mg). CNS side effects were prominent at this level, twice the rate of the placebo group. The next lower dose, 2 mg, missed the efficacy endpoint and still seemed to show CNS effects. Nearly twice the number of treated patients dropped out of the trial compared with the placebo group, citing neurological effects that included thoughts of suicide.15 Tesofensine. Another agent undergoing investigational trials is showing potential as an obesity therapy. Tesofensine has shown promising results for weight loss and distinguishes itself from rimonabant and taranabant by its mechanism of action. The serotonin–noradrenaline–dopamine reuptake inhibitor works mainly as an appetite suppressant. In a phase 2 clinical trial, the average weight loss was 12.8 kg with a 1-mg dose and 11.3 kg with a 0.5-mg dose over a sixmonth period. Adverse effects caused by the medication are mild, although an increase in blood pressure and heart rate are directly proportionate to the amount of drug administered. NeuroSearch, a company in Europe, is currently conducting an extension trial in order to determine the efficacy and safety of tesofensine. If the trial proves to be a success, tesofensine could be considered twice as effective as drugs currently available in the U.S.16 methods are unsuccessful, surgery, pharmacological options, or both should be considered. Phentermine may be used for short-term therapy, and either sibutramine or orlistat may be considered for long-term therapy. Unfortunately, rimonabant and taranabant, as cannabinoid receptor antagonists, were not approved for long-term use. With a multifaceted approach to achieve weight loss in the general population, it is hoped that many chronic diseases resulting from obesity and overweight will decline with the advent of safer drugs and more definitive studies. References 1. North American Association for the Study of Obesity (NAASO), The Obesity Society/SynerMed Communications. Identification and Treatment of Extreme Obesity: Considering Surgical Options: Frequently Asked Questions. August 2007. Available at: www.obesity.org/docs/extreme_obesity.pdf. Accessed November 10, 2008. 2. Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006; 295:1549–1555. 3. World Health Organization (WHO). Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation. Geneva, June 3–5, 1997. 4. Palamara KL, Mogul HR, Peterson SJ, Frishman WH. New obesity perspectives and pharmacotherapies. Cardiol Rev 2006; 14(5):238–258. 5. The Dietar y Guidelines for Americans 2005, Department of Health and Human Services. Available at: www.webmd.com. Accessed February 26, 2008. 6. Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyles, diabetes and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351(26):2683–2693. 7. Matarasso A, Roslin MS, Kurian M. Bariatric surger y: An overview of obesity surgery. Plastic Reconstruct Surg 2007;119(4): 1357–1362. 8. Adipex-P, package insert. Sellersville, PA: Teva Pharmaceuticals; 2005. 9. Meridia, package insert. Chicago: Abbott Laboratories; 2006. 10. Xenical, package insert. Nutley, NJ: Roche Laboratories; 2007. 11. Hickey MS, Israel RG. Obesity drugs and drugs in the pipeline. ACSM’s Health and Fitness J 2007;11(4):20–25. 12. Gokcel A, Gumurdulu Y, Karakose H, et al. Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. Diabetes Obesity Metab 2002;4:49–55. 13. Gadde K, Allison D. Cannabinoid-1 receptor antagonist, rimonabant, for management of obesity and related risks. Circulation 2006;114:974–984. 14. Merck scratches taranabant. Available at: www.taranabanthealth.com. Accessed November 10, 2008. 15. Taranabant is no more. In the pipeline. Available at: http:// pipeline.corante.com/archives/2008/03/12/taranabant_in_troub le.php. Accessed November 10, 2008. 16. Astrup A, Madsbad S, Breum L, et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: A randomised, double-blind, placebo-controlled trial. Lancet online, October 23, 2008. I Conclusion The worsening obesity epidemic has forced health care providers to be more diligent in recognizing and treating patients with weight-management problems. After appropriate assessment of a patient’s weight, changes in lifestyle regarding diet and exercise should be implemented. If traditional Conflict of Interest (COI) Statement Dr. Erlanger and Dr. Henson have no relationships to disclose. The article contains discussion of off-label use. The content of this article has been reviewed under Jefferson’s Continuing Medical Education COI policy. 728 P&T® • December 2008 • Vol. 33 No. 12 http://www.obesity.org/docs/extreme_obesity.pdf http://www.webmd.com http://www.taranabant-health.com http://www.taranabant-health.com http://pipeline.corante.com/archives/2008/03/12/taranabant_in_trouble.php http://pipeline.corante.com/archives/2008/03/12/taranabant_in_trouble.php http://pipeline.corante.com/archives/2008/03/12/taranabant_in_trouble.php

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Pharmacy & Therapeutics - December 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Interpreting Estimates of Treatment Effects Chemotherapy Foundation Symposium XXVI: Innovative Cancer Therapy for Tomorrow Third Annual Onmark National Payor/Provider Forum Fourth Annual Ophthalmic Drug Development and Delivery Summit Classification and Pharmacological Management Of Obesity CE Test and Forms Season’s Greetings: Thanks to Our Readers and Reviewers

Pharmacy & Therapeutics - December 2008

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