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Review

Safety assessment of combination therapies in the treatment of obesity: focus on naltrexone/bupropion extended release and phentermine-topiramate extended release

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Pages 27-39 | Received 14 Jul 2016, Accepted 10 Oct 2016, Published online: 24 Oct 2016

References

  • Schelbert KB. Comorbidities of obesity. Prim Care. 2009;36(2):271–285.
  • Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable to obesity in the United States. JAMA. 1999;282(16):1530–1538.
  • Flegal KM, Graubard BI, Williamson DF, et al. Cause specific excess deaths associated with underweight, overweight and obesity. JAMA. 2007;298(17):2028–2037.
  • Calle EE, Rodriguez C, Walker Thurmond K, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Eng J Med. 2003;348(17):1625–1638.
  • Dansinger ML, Tatsioni A, Wong JB, et al. Meta-analysis: the effect of dietary counseling for weight loss. Ann Intern Med. 2007;3147(1):41–50.
  • Leblanc ES, O´Connor E, Whitlock EP, et al. Effectiveness of primary care relevant treatments for obesity in adults: a systematic evidence review for the US preventive services task force. Ann Intern Med. 2011;155(7):434–447.
  • Bray GA, Frühbeck G, Ryan DH, et al. Management of obesity. Lancet. 2016;387(10031):1947–1956.
  • Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342–362.
  • Halpern B, Halpern A. Why are anti-obesity drugs stigmatized? Expert Opin Drug Saf. 2015;14(2):185–189.
  • Neff KJ, Olbers T, Le Roux CW. Bariatric surgery: the challenges with candidate selection, individualizing treatment and clinical outcomes. BMC Med. 2013;11:8.
  • Leibel RL, Seeley RJ, Darsow T, et al. Biologic responses to weight loss and weight regain: report from an American Diabetes Association Research Symposium. Diabetes. 2015;64(7):2299–2309.
  • Sumithran P, Proietto J. The defence of body weight: a physiological basis for weight regain after weight loss. Clin Sci. 2013;124(4):231–241.
  • Hussain HT, Parker JL, Sharma AM. Clinical trial success rates of anti-obesity agents: the importance of combination therapies. Obes Rev. 2015;16(9):707–714.
  • Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364–1379.
  • James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–520.
  • Halpern B, Oliveira ESL, Faria AM, et al. Combinations of drugs in the treatment of obesity. Pharmaceuticals. 2010;3(8):2398–2415.
  • Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376(9741):595–605.
  • Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–1352.
  • Colman E. Food and Drug Administration’s obesity drug guidance document: a short history. Circulation. 2012;125(17):2156–2164.
  • Weintraub M, Hasday JD, Mushlin AI, et al. A double-blind clinical trial in weight control: use of fenfluramine and phentermine alone or in combination. Arch Intern Med. 1984;144:1143–1148.
  • Hampp C, Kang EM, Borders-Hemphill V. Use of prescription antiobesity drugs in the United States. Pharmacotherapy. 2013;33(12):1299–1307.
  • Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997;337:581–588.
  • Roth BL. Drugs and valvular heart disease. N Engl J Med. 2007;356(1):6–9.
  • Meltzer HY, Roth BL. Lorcaserin and pimavanserin: emerging selectivity of serotonin receptor subtype – targeted drugs. J Clin Invest. 2013;123(12):4986–4991.
  • Astrup A, Breum L, Toubro S, et al. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine an placebo in obese subjects on an energy restricted diet. A double-blind trial. Int J Obes Relat Metab Disord. 1992;16:269–277.
  • Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing Ephedra alkaloids. N Engl J Med. 2000;343:1833–1838.
  • Geller AI, Shehab N, Weidle NJ, et al. Emergency department visits for adverse events related to dietary supplements. N Engl J Med. 2015;373:1531–1540.
  • Hendricks EJ, Rothman RB, Greenway FL. How physician obesity specialists use drugs to treat obesity. Obesity (Silver Spring). 2009;17(9):1730–1735.
  • Wadden TA, Berkowits RI, Wonble LG. Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo controlled trial. Obes Res. 2000;6:431–437.
  • Kaya A, Aydın N, Topsever P, et al. Efficacy of sibutramine, orlistat and combination therapy on short-term weight management in obese patients. Biomed Pharmacother. 2004;58:582–587.
  • Sari R, Balci MK, Coban E, et al. Comparison of the effect of orlistat vs orlistat plus metformin on weight loss and insulin resistance in obese women. Int J Obes Relat Metab Disord. 2004;28:1059–1063.
  • Greenway FL, Whitehouse MJ, Guttadauria M, et al. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring). 2009;17(1):30–39.
  • Halpern B, Faria AM, Halpern A. Bupropion/naltrexone fixed-dose combination for the treatment of obesity. Drugs Today 2011 (Barc). 2011;47(8):575–581.
  • Anderson JW, Greenway FL, Fujioka K, et al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res. 2002;10(7):633–641.
  • Lee MW, Fujioka K. Naltrexone for the treatment of obesity: review and update. Expert Opin Pharmacother. 2009;10(11):1841–1845.
  • Padwal R. Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity. Curr Opin Investig Drugs. 2009;10(10):1117–1125.
  • Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013;21:935–943.
  • Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). 2011;19(1):110–120.
  • Hollander P, Gupta AK, Plodkowski R, et al. Effects of naltrexone sustained- release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36:4022–4029.
  • Fujioka K. Safety and tolerability of medications approved for chronic weight management. Obesity (Silver Spring). 2015;23(S1):S7–S11.
  • Krentz AJ, Fujioka K, Hompesch M. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles. Diabetes Obes Metab. 2016;18(6):558–570.
  • Verpeut JL, Bello NT. Drug safety evaluation of naltrexone/bupropion for the treatment of obesity. Exp Opin Drug Saf. 2014;13(6):831–841.
  • Ascher JA, Cole JO, Colin JN, et al. Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry. 1995;56(9):395–401.
  • Wood S FDA declines approval for Contrave diet drug; asks for CVD outcomes studies. 2011 Feb 1 [cited 2016 Jun 29]. Available from: http://www.medscape.com/viewarticle/736616
  • Nissen SE, Wolski KE, Prcela L, et al. Effect of naltrexone-bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors: a randomized clinical trial. JAMA. 2016;315(10):990–1004.
  • Planer D, Lev I, Elitzur Y, et al. Bupropion for smoking cessation in patients with acute coronary syndrome. Arch Intern Med. 2011;171(12):1055–1060.
  • James WP, Caterson ID, Coutinho W, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010;363(10):905–917.
  • Sharfstein JM, Psaty BM. Evaluation of the cardiovascular risk of Naltrexone-Bupropion: a study interrupted. JAMA. 2016;315(10):984–986.
  • Davidson J. Seizures and bupropion: a review. J Clin Psychiatry. 1989;50(7):256–261.
  • Stall N, Godwin J, Juurlink D. Bupropion abuse and overdose. CMAJ. 2014;186(13):1015.
  • Macaluso M, Zackula R, D´Empaire I, et al. Twenty percent of a representative sample of patients taking bupropion have abnormal, asymptomatic electroencephalographic findings. J Clin Psychopharmacol. 2010;30(3):312–317.
  • Horne RL, Ferguson JM, Pope HG Jr., et al. Treatment of bulimia with bupropion: a multicenter controlled trial. J Clin Psychiatry. 1988;49(7):262–266.
  • Lewis JC, Sutter ME, Albertson TE, et al. An 11-year review of bupropion insufflation exposures in adults reported to the California Poison Control System. Clin Toxicol (Phila). 2014;52(9):969–972.
  • Simon GE, Savarino J, Operskalski B, et al. Suicide risk during antidepressant treatment. Am J Psychiatry. 2006;163:41–47.
  • Khan A, Khan S, Kolts R, et al. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry. 2003;160(4):790–792.
  • Wightman DS, Foster VJ, Krishen A, et al. Meta-analysis of suicidality in placebo-controlled clinical trials of adults taking bupropion. Prim Care Companion J Clin Psychiatry. 2010;12(5):pii:PCC.09m00894.
  • Hassanian-Moghaddam H, Afzali S, Pooya A. Withdrawal syndrome caused by naltrexone in opioid abusers. Human Ep Toxicol. 2014;33(6):561–567.
  • Anton RF. Naltrexone for the management of alcohol dependence. N Engl J Med. 2008;359:715–721.
  • Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295:2003–2017.
  • US Food and Drug Administration. FDA approves weight-management drug Contrave. [ cited 2016 Jun 29] Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm413896.htm
  • Symes RJ, Etminan M, Mikelberg FS. Risk of angle-closure glaucoma with bupropion and topiramate. JAMA Ophthalmol. 2015;133(10):1187–1189.
  • Stein JD, Talwar N, Kang JH, et al. Bupropion use and risk of open-angle glaucoma among enrollees in a large U.S. managed care network. PLoS One. 2015;10(4):e0123682.
  • Rothman RB, Baumann MH, Dersch CM, et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 2001;39(1):32–41.
  • Hendricks EJ, Greenway FL, Westman EC, et al. Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity (Silver Spring). 2011;19:2351–2360.
  • Kang JG, Park C-Y, Kang JH, et al. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obes Metab. 2010;12(10):876–882.
  • Jordan J, Astrup A, Engelia S, et al. Cardiovascular effects of phentermine and topiramate: a new drug combination for the treatment of obesity. J Hypertension. 2014;32:1178–1188.
  • Rothman RB, Hendricks EJ. Phentermine cardiovascular safety. Am J Emerg Med. 2009;27(8):1010–1013.
  • Hendricks EJ, Srisurapanont M, Schmidt SL, et al. Addiction potential of phentermine prescribed during long-term treatment of obesity. Int J Obes. 2014;38(2):292–298.
  • Silberstein SD, Neto W, Schmitt J, et al. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61:490–495.
  • Arnone D. Review of the use of topiramate for treatment of psychiatric disorders. Ann Gen Psychiatry. 2005;4(1):5.
  • Walker MC, Sander JW. Topiramate: a new antiepileptic drug for refractory epilepsy. Seizure. 1996;5(3):199–203.
  • Kramer CK, Leitão CB, Pinto LC, et al. Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials. Obes Rev. 2011;12(5):e338–e347.
  • Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res. 2003;11:722–733.
  • Astrup A, Caterson I, Zelissen P, et al. Topiramate: long-term maintenance of weight loss induced by a low calorie diet in obese subjects. Obes Res. 2004;12:1658–1669.
  • Shank RP, Maryanoff BE. Molecular pharmacodynamics, clinical therapeutics, and pharmacokinetics of topiramate. CNS Neurosci Ther. 2008;14:120–142.
  • Caricilli AM, Penteado E, De Abreu LL, et al. Topiramate treatment improves hypothalamic insulin and leptin signaling and action and reduces obesity in mice. Endocrinology. 2012;153(9):4401–4411.
  • Halpern B, Faria AM, Halpern A. Fixed dose combination of phentermine-topiramate for the treatment of obesity. Exp Rev Clin Pharmacol. 2013;6(3):235–241.
  • Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity. 2012;20:330–342.
  • Shah K, Villareal DT. Combination treatment to CONQUER obesity? Lancet. 2011;377(9774):1295–1297.
  • Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95:297–308.
  • Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315(22):2424–2434.
  • Garvey WT, Ryan DHM, Bohannon NJV, et al. Weight-loss therapy in type 2 diabetes: effects of phentermine and topiramate extended release. Diabetes Care. 2014;37:3309–3316.
  • Colman E, Golden J, Roberts M, et al. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med. 2012;367(17):1577–1579.
  • Wilding J, Van Gaal L, Rissanen A, et al. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes Relat Metab Disord. 2004;28(11):1399–1410.
  • Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606–613.
  • Posner K, Brent D, Lucas C, et al. Columbia-Suicide Severity Rating Scale (C-SSRS). [ cited 2016 Jun 29]. http://www.fda.gov/ohrms/dockets/ac/07/slides/2007-4306s1-01-CU-Posner_files/frame.htm
  • Colman E. Food and Drug Administration’s obesity drug guidance document: a short history. Circulation. 2012;125(17):2156–2164.
  • Drug Enforcement Administration: drug fact sheets. [ cited 2016 Jun 29]. http://www.justice.gov/dea/druginfo/concerns.shtml
  • Hendricks EJ, Greenway FL. A study of abrupt phentermine cessation in patients in a weight management program. Am J Therap. 2011;18(4):292–299.
  • Gordon AM, Logan BK. Topiramate-positive death-investigation and impaired-driving cases in Washington State. J Anal Toxicol. 2006;30(8):599–602.
  • Fountoulakis KN, Gonda X, Samara M, et al. Antiepileptic drugs and suicidality. J Psychopharmacol. 2012;26(11):1401–1407.
  • FDA. Statistical review and evaluation: antiepileptic drugs and suicidality. 2008 [cited 2016 Jun 29]. Available from: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-01-FDA.pdf
  • Procopio M. New users of the anticonvulsants gabapentin, lamotrigine, oxcarbazepine or tiagabine are at increased risk of suicidal acts compared with new users of topiramate. Evid Based Ment Health. 2010;13(4):102.
  • Wasserstein A, Reife R, Rak I. Topiramate and nephrolithiasis. Epilepsia. 1995;36(S3;S153):A205.
  • Dell´Orto VG, Belotti EA, Goeggel-Simonetti B, et al. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol. 2014;77(6):958–964.
  • Jion YI, Raff A, Grosberg BM, et al. The risk and management of kidney stones from the use of topiramate and zonisamide in migraine and idiopathic intracranial hypertension. Headache. 2015;55:161–166.
  • Wasserstein AG, Rak I, Reife RA. Nephrolithiasis during treatment with topiramate. Epilepsia. 1995;36(Suppl 3):S153.
  • Kuo RL, Moran ME, Kim DH, et al. Topiramate-induced nephrolithiasis. J Endourol. 2002;16(4):229–231.
  • Vajda FJ, Graham J, Roten A, et al. Teratogenicity of the newer antiepileptic drugs – the Australian experience. J Clin Neurosci. 2012;19(1):57–59.
  • Tennis P, Chan KA, Curkendall SM, et al. Topiramate use during pregnancy and major congenital malformations in multiple populations. Birth defects Res A Clin Mol Teratol. 2015;103(4):269–275.
  • Shin J, Gadde K. Clinical utility of phentermine/topiramate (Qsymia) combination for the treatment of obesity. Diabetes Metab Syndr Obes. 2013;6:131–139.
  • Reddy DS. Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives. Expert Rev Clin Pharmacol. 2010;3(2):183–192.
  • Sabers A. Pharmacokinetic interactions between contraceptives and antiepileptic drugs. Seizure. 2008;17(2):141–144.
  • Liu Y, Rhee DJ. Acute bilateral angle closure. JAMA Ophthalmol. 2013;131(9):1231–1232.
  • Abtahi M-A, Abtahi S-H, Fazel F, et al. Topiramate and the vision: a systematic review. Clin Ophthalmol. 2012;6:117–131.
  • Lorcaserin and phentermine safe combo in weight-loss trial. Medscape Medical News. [cited 2016 Jun 29]. Available from: http://www.medscape.com/viewarticle/834676
  • clinicaltrials.gov. Effects of Co-administration of Canagliflozin 300 mg and Phentermine 15 mg With Placebo in the Treatment of Non-Diabetic Overweight and Obese Participants. [ cited 2016 Jun 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT02243202
  • Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128.
  • Sattar N, McLaren J, Kristensen SL, et al. SGLT2 inhibition and cardiovascular events: why did EMPA-REG outcomes surprise and what were the likely mechanisms? Diabetologia. 2016;59(7):1333–1339.
  • 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. 2008;372(9653):1906–1931.
  • Tsai AG. Tesofensine and weight loss. Lancet. 2009;373(9665):719.
  • Bentzen BH, Grunnet M, Hyveled-Nielsen L, et al. Anti-hypertensive treatment preserves appetite suppression while preventing cardiovascular adverse effects of tesofensine in rats. Obesity (Silver Spring). 2013;21(5):985–992.
  • clinicaltrials.gov. Safety and Efficacy Study of Tesofensine/Metoprolol Treatment in Subjects With Type 2 Diabetes Mellitus. [ cited 2016 Jun 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT02737891?term=tesofensine+metoprolol&rank=1
  • Zhang S, Manne S, Lin J, et al. Characteristics of patients potentially eligible for pharmacotherapy for weight loss in primary care practice in the United States. Obes Sci Pract. 2016;2:104–114.
  • Samaranayake NR, Ong KL, Leung RYH, et al. Management of obesity in the National Health and Nutrition Examination Survey (NHANES), 2007-2008. Ann Epidemiol. 2012;22(5):349–353.
  • Vamado PJ, Williamson DA, Bentz BG, et al. Prevalence of binge eating disorder in obese adults seeking weight loss treatment. Eat Weight Disord. 1997;2(3):117–124.
  • Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11–22.
  • Field AE, Camargo CA Jr. The merits of subtyping obesity one size does not fit all. JAMA. 2013;310(20):2147–2148.

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