Naltrexone/bupropion: Difference between revisions

2278:] submitted a ] (NDA) for the combination to the FDA in March 2010.<ref>{{Cite press release |url=https://www.prnewswire.com/news-releases/orexigenr-therapeutics-submits-contraver-new-drug-application-to-fda-for-the-treatment-of-obesity-89626217.html |title=Orexigen Therapeutics Submits Contrave New Drug Application to FDA for the Treatment of Obesity |publisher=Orexigen Therapeutics |via=PR Newswire |access-date=2 July 2024 |archive-date=25 April 2023 |archive-url=https://web.archive.org/web/20230425110900/https://www.prnewswire.com/news-releases/orexigenr-therapeutics-submits-contraver-new-drug-application-to-fda-for-the-treatment-of-obesity-89626217.html |url-status=live }}</ref> Having paid a fee under the ], Orexigen was given a deadline for the FDA to approve or reject the drug of January 2011. In December 2010, an FDA Advisory Committee voted 13-7 for the approval of Contrave, and voted 11-8 for the conduct of a post-marketing cardiovascular outcomes study.<ref name="Orexigen Therapeutics, Inc. 2010">{{cite web | title=Press Release | website=Orexigen Therapeutics, Inc. | date=7 December 2010 |url=http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irol-newsArticle&ID=1505602&highlight= | access-date=29 December 2016 }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Subsequently, on 2 February 2011, the FDA rejected the drug and it was decided that an extremely large-scale study of the long-term cardiovascular effects of Contrave would be needed, before approval could be considered.<ref> {{Webarchive|url=https://web.archive.org/web/20161230090426/https://www.drugs.com/nda/contrave_110204.html |date=30 December 2016 }}, ]</ref> It was ultimately approved in the United States in 2014.<ref name=fda20140911>{{cite press release |publisher=] |date=10 September 2014 |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm413896.htm |title=FDA approves weight-management drug Contrave |access-date=16 December 2019 |archive-date=17 February 2017 |archive-url=https://web.archive.org/web/20170217225439/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm413896.htm |url-status=dead }}</ref> 1856:(FDA) | date=12 November 2014 |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/200063Orig1s000TOC.cfm | access-date=5 August 2020 | archive-date=4 June 2020 | archive-url=https://web.archive.org/web/20200604184413/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/200063Orig1s000TOC.cfm | url-status=live }}</ref><ref name=fda20140911 /> The combination was subsequently approved in the ] in the spring of 2015, where it is sold under the name Mysimba.<ref name="Mysimba EPAR">{{cite web | title=Mysimba EPAR | website=] (EMA) | date=17 September 2018 |url=https://www.ema.europa.eu/en/medicines/human/EPAR/mysimba | access-date=5 August 2020 | archive-date=22 October 2020 | archive-url=https://web.archive.org/web/20201022220427/https://www.ema.europa.eu/en/medicines/human/EPAR/mysimba | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref name=Orexigen2015>{{cite news|last1=Orexigen Therapeutics, Inc.|title=Orexigen's Mysimba Approved in Europe for the Treatment of Obesity|url=https://finance.yahoo.com/news/orexigens-mysimba-approved-europe-treatment-182200956.html|access-date=28 March 2015|work=Yahoo! Finance|agency=PR Newswire|date=26 March 2015|archive-date=31 March 2015|archive-url=https://web.archive.org/web/20150331053050/http://finance.yahoo.com/news/orexigens-mysimba-approved-europe-treatment-182200956.html|url-status=live}}</ref> It was approved in Canada under the Contrave brand name in 2018.<ref>{{cite web | title=Regulatory Decision Summary — Contrave — Health Canada | website=] | date=13 February 2018 |url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00417 | access-date=5 September 2021 | archive-date=4 December 2020 | archive-url=https://web.archive.org/web/20201204015341/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00417 | url-status=live }}</ref> 2320:

releasing interim data. The early data release reported a reduction in heart attacks, but that advantage was no longer observed when a more complete view of the data was analyzed.<ref name="Silverman 2015">{{cite web | last=Silverman | first=Ed | title=Orexigen Study for Diet Drug Ends Over Premature Data Disclosure | website=WSJ | date=12 May 2015 |url=https://blogs.wsj.com/pharmalot/2015/05/12/orexigen-safety-study-for-diet-pill-ends-due-to-premature-data-disclosure/ | access-date=29 December 2016 | archive-date=30 December 2016 | archive-url=https://web.archive.org/web/20161230003226/http://blogs.wsj.com/pharmalot/2015/05/12/orexigen-safety-study-for-diet-pill-ends-due-to-premature-data-disclosure/ | url-status=live }}</ref> The company then initiated a second trial (CONVENE) designed to test this outcome in 2016, but it was terminated in 2016 shortly after Takeda announced that it would sell its rights to the drug in the USA to Orexigen.<ref name="ORiordan2016">{{cite news |last1=O'Riordan |first1=Michael |title=Another CV Outcomes Trial Testing Weight-Loss Drug Contrave Terminated Early |url=https://www.tctmd.com/news/another-cv-outcomes-trial-testing-weight-loss-drug-contrave-terminated-early |access-date=20 May 2024 |work=] |publisher=] |date=14 April 2016 |archive-date=20 May 2024 |archive-url=https://web.archive.org/web/20240520212807/https://www.tctmd.com/news/another-cv-outcomes-trial-testing-weight-loss-drug-contrave-terminated-early |url-status=live }}</ref>

1830:| year = 2007 | volume = 15 | issue = 9 | pages = A179}}</ref> In clinical trials, patients taking Contrave combined with diet and exercise lost more weight than patients taking a placebo and following the same diet and exercise program.<ref>, ''Medical News Today'', 28 Sep 2006</ref> On 31 March 2010, Orexigen submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for this drug combination.<ref></ref> On 7 December 2010, an FDA Advisory Committee voted 13-7 for the approval of Contrave, and voted 11-8 for the conduct of a post-marketing cardiovascular outcomes study.<ref></ref> Contrave's ] date is 31 January 2011. Subsequently, on 2 February 2011, the FDA rejected the drug and it was decided that an extremely large-scale study of the long-term cardiovascular effects of Contrave would be needed, before approval could be considered.<ref> </ref> The recommended daily dose of Contrave is two (8 mg naltrexone/90 mg bupropion) tablets taken twice daily (4 tablets total - 32 mg naltrexone, 360 mg bupropion). Upon initiation, the drug will be started with a quarter-dose (or one tablet) for one week and a pill will be added to the regimen each week until the full recommended dose is reached on Week 4. 2341:|url=https://www.sandiegouniontribune.com/business/biotech/sd-me-orexigen-sold-nalpropion-20180423-story.html | access-date=5 August 2020 | archive-date=13 October 2018 | archive-url=https://web.archive.org/web/20181013150743/http://www.sandiegouniontribune.com/business/biotech/sd-me-orexigen-sold-nalpropion-20180423-story.html | url-status=live }}</ref><ref>{{cite press release | title=Nalpropion Pharmaceuticals, Inc. Expands Agreement with iNova Pharmaceuticals for Exclusive Commercialization Rights for Contrave (naltrexone HCl / bupropion HCl extended release) to include Select Markets in Southeast Asia, Africa and the Pacific | publisher=Nalpropion Pharmaceuticals | via=GlobeNewswire | date=19 December 2018 |url=http://www.globenewswire.com/news-release/2018/12/19/1669738/0/en/Nalpropion-Pharmaceuticals-Inc-Expands-Agreement-with-iNova-Pharmaceuticals-for-Exclusive-Commercialization-Rights-for-Contrave-naltrexone-HCl-bupropion-HCl-extended-release-to-inc.html | access-date=5 August 2020 | archive-date=28 October 2021 | archive-url=https://web.archive.org/web/20211028140715/https://www.globenewswire.com/Content/css/bootstrap.min.css | url-status=live }}</ref> 888:| legal_CA_comment =<ref>{{cite web | title=Regulatory Decision Summary — Contrave | website=Health Canada | date=23 October 2014 |url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00417 | access-date=7 June 2022 | archive-date=4 December 2020 | archive-url=https://web.archive.org/web/20201204015341/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00417 | url-status=live }}</ref><ref>{{cite web | title=Drug and medical device highlights 2018: Helping you maintain and improve your health | website=] | date=14 October 2020 |url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/drug-medical-device-highlights-2018.html | access-date=17 April 2024 | archive-date=17 April 2024 | archive-url=https://web.archive.org/web/20240417063539/https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/drug-medical-device-highlights-2018.html | url-status=live }}</ref> 2247:

and obesity-related risk factors (COR-II) | journal = Obesity | volume = 21 | issue = 5 | pages = 935–43 | date = May 2013 | pmid = 23408728 | pmc = 3739931 | doi = 10.1002/oby.20309 }}</ref> In 2009, ] physiologist Michael Cowley was awarded one of ]'s top research honors, the Commonwealth Science Minister's Prize for Life Scientist of the Year, in recognition of his elucidation of these pathways, which led to the development of the combination medication.<ref name=monashnews2009>{{cite web |url=http://www.monash.edu.au/news/newsline/story/1534 |title=Obesity expert named Life Scientist of the Year |publisher=] |url-status=dead |date=29 October 2009 |archive-date=2 November 2009 |archive-url=https://web.archive.org/web/20091102061153/http://www.monash.edu.au/news/newsline/story/1534 }}</ref>

2153:]<ref>{{Cite web |title=Suicidality in Children and Adolescents Being Treated With Antidepressant Medications |url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/suicidality-children-and-adolescents-being-treated-antidepressant-medications |access-date=21 February 2024 |website=United States Food and Drug Administration. |date=3 November 2018 |archive-date=23 August 2020 |archive-url=https://web.archive.org/web/20200823034643/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/suicidality-children-and-adolescents-being-treated-antidepressant-medications |url-status=live }}</ref> 2226:*Naltrexone is a pure opioid antagonist, which further augments bupropion's activation of the POMC.<ref>{{cite journal | vauthors = Greenway FL, Whitehouse MJ, Guttadauria M, Anderson JW, Atkinson RL, Fujioka K, Gadde KM, Gupta AK, O'Neil P, Schumacher D, Smith D, Dunayevich E, Tollefson GD, Weber E, Cowley MA | title = Rational design of a combination medication for the treatment of obesity | journal = Obesity | volume = 17 | issue = 1 | pages = 30–9 | date = January 2009 | pmid = 18997675 | doi = 10.1038/oby.2008.461 | s2cid = 24856014 | doi-access = free }}</ref> 976:| legal_US_comment =<ref name="Contrave FDA label">{{cite web | title=Contrave Extended-Release- naltrexone hydrochloride and bupropion hydrochloride tablet, extended release | website=DailyMed | date=26 April 2019 |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=485ff360-32c8-11df-928b-0002a5d5c51b | access-date=5 August 2020 | archive-date=4 June 2020 | archive-url=https://web.archive.org/web/20200604190921/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=485ff360-32c8-11df-928b-0002a5d5c51b | url-status=live }}</ref> 2384:|url=http://seekingalpha.com/article/3159646-orexigen-posts-loss-revenue-will-be-the-story |title=Orexigen Posts Loss — Revenue Will Be The Story |website=Seeking Alpha |date=8 May 2015 |last=Osborne |first=Spencer |type=blog |access-date=9 May 2015 |archive-date=10 May 2015 |archive-url=https://web.archive.org/web/20150510014235/http://seekingalpha.com/article/3159646-orexigen-posts-loss-revenue-will-be-the-story |url-status=live }}</ref> 2024:

October 2021 |archive-url=https://web.archive.org/web/20211002200557/https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf |url-status=live }}</ref> Once full dosing is reached (after 4 weeks of administration), the total dosage of Contrave for overweightness or obesity is two tablets twice daily or 32 mg naltrexone and 360 mg bupropion per day.<ref name="ContraveLabel" />

2299:|url=http://www.fiercepharma.com/regulatory/orexigen-s-weight-loss-drug-gets-thumbs-up-from-chmp | access-date=29 December 2016 | archive-date=30 December 2016 | archive-url=https://web.archive.org/web/20161230001640/http://www.fiercepharma.com/regulatory/orexigen-s-weight-loss-drug-gets-thumbs-up-from-chmp | url-status=live }}</ref> Approval was granted in March 2015.<ref name=Orexigen2015 /> 2023:

Each Contrave tablet contains 8 mg naltrexone and 90 mg bupropion.<ref name="ContraveLabel">{{cite web |title=CONTRAVE (naltrexone HCl and bupropion HCl) |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf |access-date=10 July 2024 |archive-date=2

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Combined, naltrexone/bupropion has an effect on the reward pathway that results in reduced food craving.<ref>{{cite journal | vauthors = Apovian CM, Aronne L, Rubino D, Still C, Wyatt H, Burns C, Kim D, Dunayevich E | title = A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight

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Treatment is designed to influence the ] in order to decrease food intake over an extended period of time. Studies of almost 700 patients, 90% female, ran up to 56 weeks. The control group, overall, lost 5% of their initial body weight, or 11-16 lbs. The experimental (medicated) group lost

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In September 2014, a ] formulation of the drug was approved for marketing in the United States under the brand name '''Contrave'''.<ref>{{cite web | title=Drug Approval Package: Contrave (naltrexone hydrochloride/bupropion hydrochloride) Extended-Release Tablets NDA #200063 | website=U.S. ]

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The FDA has issued a ] regarding an increased risk for suicidal thoughts and behavior in children, adolescents, and young adults under the age of 25.<ref name ="Contrave FDA label" /> This is attributed to the bupropion component, as the FDA requires all ] to include that boxed warning on

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In May 2015, Orexigen prematurely ended the trial that was intended to test whether naltrexone/bupirion increased the risk of ] in obese patients with cardiovascular disease, because an independent panel of experts said that the drug maker “inappropriately” compromised the trial by prematurely

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In December 2014, the EU's ] (CHMP) endorsed the combination for licensure as an obesity medication when used alongside diet and exercise.<ref name=Palmer2014>{{cite news | title=Orexigen's weight-loss drug gets thumbs-up from CHMP | newspaper=Fierce Pharma | date=19 December 2014

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The sustained-release formulation, Contrave, is marketed by ] under license from the combination medication's developer, Orexigen Therapeutics.<ref name=fda20140911 /> As of 2015, Orexigen received 20% of net sales from Takeda.<ref name="osborne2015">{{cite web

204: 2215:*Bupropion is a ] of both ] and ], and a ] ], and it activates ] (POMC) neurons in the ] which give an effect downstream, resulting in loss of appetite and increased energy output. The POMC is regulated by ] via opioid-mediated ].{{medcn|date=August 2020}} 1992:* 27 kg/m2 to < 30 kg/m2, (overweight) in the presence of one or more weight-related ], like ], ], or controlled ]<ref name="Contrave FDA label"/><ref name="Mysimba EPAR" /> 1979:

20-23 lbs during the same amount of time. The average starting weight for participants was 223 lbs.<ref></ref> Current ] medications average 5-22 lbs lost in 6 months.<ref></ref>{{verify credibility}}

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In 2018, Orexigen sold its assets, including Contrave, to Nalpropion Pharmaceuticals.<ref>{{cite news | title=Orexigen, seller of weight-loss drug Contrave, agrees to sale for $ 75 million | website=San Diego Union-Tribune | date=23 April 2018

1945:

Naltrexone/bupropion is indicated, as an adjunct to a reduced-calorie diet and increased physical activity, as ] for the management of weight in adults with an initial ] (BMI) of:<ref name="Contrave FDA label"/><ref name="Mysimba EPAR"

78: 35: 86: 92: 49: 11: 43: 187: 57: 1625:| title = Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity | journal = Expert Opinion on Pharmacotherapy | 1364:| title = Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity | journal = Expert Opinion on Pharmacotherapy | 218: 116: 100: 211: 168: 161: 943:| legal_UK =  2055:

According to the ] (FDA), naltrexone/bupropion is contraindicated in patients who have/are:<ref name ="Contrave FDA label"/>

195: 157: 1969:* 30 kg/m2 (obese), or<ref name="Contrave FDA label"/><ref name="Mysimba EPAR" /> 24: 199: 2173:

The safety and effectiveness in children under the age of 18 has not been studied.<ref name="Contrave FDA label" />

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Individually, naltrexone and bupropion each target pathways in the ] that influence appetite and energy use.

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2016 | pmid = 27217728 | pmc = 4862388 | doi = 10.2147/PPA.S84778 | doi-access = free }}</ref>

58: 44: 175: 1865:

During phase 2 testing, different dosages were used in a once daily formula. These include:

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have individually shown some evidence of effectiveness in weight loss, and the combination

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have individually shown some evidence of effectiveness in weight loss, and the combination

101: 692:| Drugs.com = {{drugs.com|monograph|naltrexone-hydrochloride-and-bupropion-hydrochloride}} 8: 1776:

HCI for chronic weight management in obese adults: patient selection and perspectives

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The second dosage (32 mg-400 mg) on average showed the best benefit-to-risk ratio.

132: 239: 454:| caption = Skeletal structures of bupropion (top) and naltrexone (bottom) 833:| legal_AU =  635:| legal_AU =  233:

Bupropion is not a releasing agent. It acts only as a reuptake inhibitor.

701:| legal_US =  657:| legal_CA =  593:| pregnancy_US =  571:| pregnancy_AU =  112: 111: 1009:| legal_UN =  1031:| legal_status =  679:| legal_UK =  899:| legal_DE =  714:| pregnancy_AU =  483:| ATC_prefix =  273:{{Short description|Medication for treatment of obesity}} 1876:* 16 mg naltrexone - 400 mg bupropion 1898:* 48 mg naltrexone - 400 mg bupropion 1887:* 32 mg naltrexone - 400 mg bupropion 139: 998:| legal_EU_comment =<ref name="Mysimba EPAR" /> 295:{{cs1 config|name-list-style=vanc|display-authors=6}} 255:(162 intermediate revisions by 68 users not shown) 2077:* History of an eating disorder such as ] or ] 196:Latest revision as of 19:28, 10 September 2024 2088:* Taking ]s, or are in opiate withdrawal. 1247: 921:| legal_NZ =  2121:* Abruptly stopped use of ], ], ], or ] 1583:<ref name="Contrave FDA label" /> 1139:| KEGG_Ref = {{keggcite|changed|kegg}} 388:| image = Bupropion and naltrexone.svg 77: 34: 2534:{{DEFAULTSORT:Naltrexone Bupropion}} 1657:| doi = 10.1517/14656560902775750 | 1435:a combination of two approved drugs, 1396:| doi = 10.1517/14656560902775750 | 148: 131: 254: 237: 224: 210: 193: 186: 181: 167: 155: 9: 120: 2643: 158:Revision as of 03:00, 5 June 2011 95: 81: 52: 38: 419:| component2 = Naltrexone 284:{{Use dmy dates|date=July 2024}} 1726:name="Contrave FDA label" /> 670:| tradename = Contrave, Mysimba 375:| component1 = Bupropion 769:| routes_of_administration = ] 1: 2628: 2617: 2606: 2595: 2584: 2573: 2562: 2555: 2530: 2507: 2496: 2485: 2474: 2463: 2452: 2443: 2428: 2417: 2379: 2368: 2357: 2348: 2336: 2327: 2315: 2306: 2294: 2285: 2274: 2263: 2254: 2242: 2233: 2222: 2211: 2200: 2189: 2180: 2169: 2160: 2148: 2137: 2128: 2117: 2106: 2099:* Taken ] in the last 14 days 2095: 2084: 2073: 2062: 2051: 2040: 2031: 2019: 2008: 1999: 1988: 1974: 1965: 1941: 1928: 1919: 1894: 1883: 1872: 1861: 1851: 1826: 1749:.<ref>{{cite journal | 1537: 1462:.<ref>{{cite journal | 1317:.<ref>{{cite journal | 1280: 1243: 1234: 1223: 1212: 1201: 1190: 1179: 1168: 1157: 1146: 1135: 1124: 1113: 1102: 1091: 1080: 1069: 1058: 1047: 1038: 1027: 1016: 1005: 994: 983: 972: 961: 950: 939: 928: 917: 906: 895: 884: 873: 862: 851: 840: 829: 818: 809: 798: 787: 776: 765: 754: 745:| routes_of_administration = 741: 732: 719: 710: 697: 688: 675: 666: 653: 644: 631: 624: 611: 602: 589: 580: 567: 558: 545: 536: 523: 514: 501: 492: 479: 472: 459: 450: 437: 428: 415: 406: 393: 384: 371: 362: 349: 340: 327: 318: 291: 280: 269: 1655:April 2009 | pmid = 19364254 1585:<ref>{{cite journal | 1576:adults in combination with a 1406:Currently being developed by 648: 14:Browse history interactively 7: 1062:| CAS_number = 1201668-08-7 822: 366:| verifiedrevid = 432618382 353:| type = combo 331:| verifiedrevid = 414493049 2648: 1051: 322:| Verifiedfields = changed 226: 2626: 2615: 2604: 2593: 2582: 2571: 2528: 2505: 2500:{{Portal bar | Medicine}} 2494: 2483: 2472: 2461: 2450: 2441: 2377: 2366: 2355: 2346: 2334: 2325: 2313: 2304: 2292: 2283: 2272: 2261: 2252: 2240: 2231: 2220: 2209: 2198: 2187: 2178: 2167: 2158: 2146: 2135: 2126: 2115: 2104: 2093: 2082: 2071: 2060: 2049: 2038: 2029: 2017: 2006: 1997: 1986: 1982: 1963: 1939: 1935: 1917: 1901: 1890: 1879: 1868: 1849: 1833: 1572:the management of chronic 1241: 1232: 1221: 1210: 1199: 1188: 1177: 1166: 1155: 1144: 1133: 1122: 1111: 1100: 1089: 1078: 1067: 1056: 1045: 1036: 1025: 1014: 1003: 992: 981: 970: 959: 948: 937: 926: 915: 904: 893: 882: 871: 860: 849: 838: 827: 816: 807: 796: 785: 774: 763: 752: 748: 736:| pregnancy_AU_comment = 730: 726: 708: 704: 686: 682: 664: 660: 642: 638: 622: 618: 600: 596: 578: 574: 556: 552: 540:| component1 = Naltrexone 534: 530: 512: 508: 496: 490: 486: 470: 466: 448: 444: 441:| class2 = ] ] 426: 422: 404: 400: 397:| class1 = ]/] 382: 378: 360: 356: 344:| Watchedfields = changed 338: 334: 316: 289: 278: 267: 262: 259: 192: 154: 584:| component2 = Bupropion 2361:==Society and culture== 2193:==Mechanism of action== 615:| pregnancy_category= 153: 758:| pregnancy_category= 723:| legal_status = 549:| DrugBank = 527:| PubChem = 505:| ATC_suffix = 463:| CAS_number = 2511:{{Authority control}} 2044:==Contraindications== 2012:===Available forms=== 1117:| ChemSpiderID_Ref = 1020:| legal_UN_comment = 954:| legal_UK_comment = 932:| legal_NZ_comment = 910:| legal_DE_comment = 866:| legal_BR_comment = 844:| legal_AU_comment = 229:→‎Mechanism of action 1073:| PubChem = 11556075 987:| legal_EU = Rx-only 965:| legal_US = Rx-only 877:| legal_CA = Rx-only 802:| ATC_supplemental = 606:| class2 = ] and ] ] 109: 66: 2141:==Adverse effects== 1559:name '''Contrave''' 1299:name '''Contrave''' 791:| ATC_suffix = AA62 69: 26: 1784:Patient Preference 1084:| IUPHAR_ligand = 780:| ATC_prefix = A08 208: 165: 74: 31: 2636: 1747:effects on weight 1425:sustained-release 1205:| NIAID_ChemDB = 1128:| ChemSpiderID = 1095:| DrugBank_Ref = 194: 156: 97: 83: 70: 54: 40: 27: 2639: 2489:{{Opioidergics}} 2478:{{Cholinergics}} 1923:==Medical uses== 1581:and increased ]. 1404:}}</ref> 249: 248: 245: 235: 234: 232: 222: 207: 202: 184: 179: 164: 145: 144: 142: 137: 135: 127: 124: 113: 98: 84: 73: 55: 41: 30: 17: 15: 2647: 2646: 2642: 2641: 2640: 2638: 2637: 2633: 2622: 2611: 2600: 2589: 2578: 2567: 2560: 2551: 2544: 2535: 2524: 2519: 2512: 2501: 2490: 2479: 2468: 2467:{{Adrenergics}} 2457: 2446: 2437: 2435: 2426: 2424: 2413: 2406: 2397: 2392: 2385: 2373: 2372:===Economics=== 2362: 2351: 2342: 2330: 2321: 2309: 2300: 2288: 2279: 2268: 2257: 2248: 2236: 2227: 2216: 2205: 2194: 2183: 2174: 2163: 2154: 2142: 2131: 2122: 2111: 2100: 2089: 2078: 2067: 2056: 2045: 2034: 2025: 2013: 2002: 1993: 1980: 1970: 1959: 1954: 1947: 1933: 1924: 1913: 1908: 1899: 1888: 1877: 1866: 1857: 1845: 1840: 1831: 1822: 1821: 1817: 1813: 1810: 1807: 1804: 1801: 1798: 1795: 1792: 1789: 1785: 1781: 1777: 1774: 1771: 1768: 1765: 1762: 1759: 1756: 1752: 1748: 1745: 1742: 1738: 1735: 1731: 1727: 1724: 1720: 1716: 1713: 1710: 1707: 1704: 1700: 1696: 1693: 1690: 1687: 1684: 1681: 1678: 1675: 1671: 1668: 1665:}}</ref> 1664: 1660: 1656: 1652: 1648: 1644: 1640: 1636: 1632: 1628: 1624: 1620: 1617: 1613: 1610: 1606: 1603: 1599: 1596: 1592: 1588: 1584: 1579: 1577: 1573: 1569: 1566: 1562: 1558: 1555: 1552: 1548: 1544: 1535: 1534: 1530: 1526: 1523: 1520: 1517: 1514: 1511: 1508: 1507:synergistically 1505: 1502: 1498: 1494: 1490: 1487: 1484: 1481: 1478: 1475: 1472: 1469: 1465: 1461: 1457: 1453: 1450: 1446: 1441: 1438: 1436: 1432: 1429: 1426: 1423: 1420: 1417: 1413: 1410:<ref>< 1407: 1403: 1399: 1395: 1391: 1387: 1383: 1379: 1375: 1371: 1367: 1363: 1360: 1356: 1352: 1348: 1345: 1341: 1338: 1334: 1331: 1327: 1324: 1320: 1316: 1312: 1309: 1306: 1302: 1298: 1295: 1291: 1287: 1276: 1271: 1264: 1257: 1248: 1237: 1228: 1217: 1216:| PDB_ligand = 1206: 1195: 1184: 1183:| ChEMBL_Ref = 1173: 1162: 1151: 1150:| KEGG = D10751 1140: 1129: 1118: 1107: 1096: 1085: 1074: 1063: 1052: 1041: 1032: 1021: 1010: 999: 988: 977: 966: 955: 944: 933: 922: 911: 900: 889: 878: 867: 856: 845: 834: 823: 812: 803: 792: 781: 770: 759: 746: 737: 724: 715: 702: 693: 680: 671: 658: 649: 636: 627: 616: 607: 594: 585: 572: 563: 550: 541: 528: 519: 506: 497: 484: 475: 464: 455: 442: 433: 420: 411: 398: 389: 376: 367: 354: 345: 332: 323: 312: 305: 296: 285: 274: 250: 247:Mobile web edit 246: 243: 238: 236: 227: 225: 223: 216: 214: 209: 203: 198: 190: 188:← Previous edit 185: 182: 180: 173: 171: 166: 160: 152: 151: 150: 149: 147: 146: 140: 138: 133: 130: 128: 125: 123:Content deleted 122: 119: 117:← Previous edit 114: 110: 108: 107: 106: 105: 104: 103: 102: 94: 91: 90: 89: 88: 80: 71: 67: 65: 64: 63: 62: 61: 60: 59: 51: 48: 47: 46: 45: 37: 28: 22: 21: 20: 13: 5: 2645: 2635: 2634: 2631: 2629: 2627: 2624: 2623: 2620: 2618: 2616: 2613: 2612: 2609: 2607: 2605: 2602: 2601: 2598: 2596: 2594: 2591: 2590: 2587: 2585: 2583: 2580: 2579: 2576: 2574: 2572: 2569: 2568: 2565: 2563: 2561: 2558: 2556: 2553: 2552: 2549: 2547: 2545: 2542: 2540: 2537: 2536: 2533: 2531: 2529: 2526: 2525: 2522: 2520: 2517: 2514: 2513: 2510: 2508: 2506: 2503: 2502: 2499: 2497: 2495: 2492: 2491: 2488: 2486: 2484: 2481: 2480: 2477: 2475: 2473: 2470: 2469: 2466: 2464: 2462: 2459: 2458: 2456:{{Anorectics}} 2455: 2453: 2451: 2448: 2447: 2444: 2442: 2439: 2438: 2433: 2431: 2429: 2427: 2422: 2420: 2418: 2415: 2414: 2412:==References== 2411: 2409: 2407: 2405:==References== 2404: 2402: 2399: 2398: 2395: 2393: 2390: 2387: 2386: 2382: 2380: 2378: 2375: 2374: 2371: 2369: 2367: 2364: 2363: 2360: 2358: 2356: 2353: 2352: 2349: 2347: 2344: 2343: 2339: 2337: 2335: 2332: 2331: 2328: 2326: 2323: 2322: 2318: 2316: 2314: 2311: 2310: 2307: 2305: 2302: 2301: 2297: 2295: 2293: 2290: 2289: 2286: 2284: 2281: 2280: 2277: 2275: 2273: 2270: 2269: 2266: 2264: 2262: 2259: 2258: 2255: 2253: 2250: 2249: 2245: 2243: 2241: 2238: 2237: 2234: 2232: 2229: 2228: 2225: 2223: 2221: 2218: 2217: 2214: 2212: 2210: 2207: 2206: 2203: 2201: 2199: 2196: 2195: 2192: 2190: 2188: 2185: 2184: 2181: 2179: 2176: 2175: 2172: 2170: 2168: 2165: 2164: 2161: 2159: 2156: 2155: 2151: 2149: 2147: 2144: 2143: 2140: 2138: 2136: 2133: 2132: 2129: 2127: 2124: 2123: 2120: 2118: 2116: 2113: 2112: 2109: 2107: 2105: 2102: 2101: 2098: 2096: 2094: 2091: 2090: 2087: 2085: 2083: 2080: 2079: 2076: 2074: 2072: 2069: 2068: 2066:* History of ] 2065: 2063: 2061: 2058: 2057: 2054: 2052: 2050: 2047: 2046: 2043: 2041: 2039: 2036: 2035: 2032: 2030: 2027: 2026: 2022: 2020: 2018: 2015: 2014: 2011: 2009: 2007: 2004: 2003: 2000: 1998: 1995: 1994: 1991: 1989: 1987: 1984: 1983: 1981: 1977: 1975: 1972: 1971: 1968: 1966: 1964: 1961: 1960: 1957: 1955: 1952: 1949: 1948: 1944: 1942: 1940: 1937: 1936: 1934: 1931: 1929: 1926: 1925: 1922: 1920: 1918: 1915: 1914: 1911: 1909: 1906: 1903: 1902: 1900: 1897: 1895: 1892: 1891: 1889: 1886: 1884: 1881: 1880: 1878: 1875: 1873: 1870: 1869: 1867: 1864: 1862: 1859: 1858: 1854: 1852: 1850: 1847: 1846: 1843: 1841: 1838: 1835: 1834: 1832: 1829: 1827: 1824: 1823: 1819: 1815: 1811: 1808: 1805: 1802: 1799: 1796: 1793: 1790: 1787: 1783: 1779: 1775: 1772: 1769: 1766: 1763: 1760: 1757: 1754: 1750: 1746: 1743: 1740: 1736: 1733: 1729: 1725: 1722: 1718: 1714: 1711: 1708: 1705: 1703:name="Contrave 1702: 1698: 1697: 1694: 1691: 1688: 1685: 1682: 1679: 1676: 1673: 1669: 1666: 1662: 1658: 1654: 1650: 1646: 1642: 1638: 1634: 1630: 1626: 1622: 1618: 1615: 1611: 1608: 1604: 1601: 1597: 1594: 1590: 1586: 1582: 1580: 1575: 1571: 1567: 1564: 1560: 1556: 1554:sold under the 1553: 1550: 1546: 1542: 1540: 1538: 1536: 1532: 1528: 1524: 1521: 1518: 1515: 1512: 1509: 1506: 1503: 1500: 1496: 1492: 1488: 1485: 1482: 1479: 1476: 1473: 1470: 1467: 1463: 1459: 1455: 1451: 1448: 1444: 1442: 1439: 1434: 1430: 1427: 1424: 1421: 1418: 1415: 1411: 1409: 1405: 1401: 1397: 1393: 1389: 1385: 1381: 1377: 1373: 1369: 1365: 1361: 1358: 1354: 1350: 1346: 1343: 1339: 1336: 1332: 1329: 1325: 1322: 1321:= Plodkowski, 1318: 1314: 1310: 1307: 1304: 1300: 1296: 1293: 1289: 1285: 1283: 1281: 1278: 1277: 1274: 1272: 1269: 1266: 1265: 1262: 1260: 1258: 1255: 1253: 1250: 1249: 1246: 1244: 1242: 1239: 1238: 1235: 1233: 1230: 1229: 1226: 1224: 1222: 1219: 1218: 1215: 1213: 1211: 1208: 1207: 1204: 1202: 1200: 1197: 1196: 1193: 1191: 1189: 1186: 1185: 1182: 1180: 1178: 1175: 1174: 1171: 1169: 1167: 1164: 1163: 1161:| ChEBI_Ref = 1160: 1158: 1156: 1153: 1152: 1149: 1147: 1145: 1142: 1141: 1138: 1136: 1134: 1131: 1130: 1127: 1125: 1123: 1120: 1119: 1116: 1114: 1112: 1109: 1108: 1105: 1103: 1101: 1098: 1097: 1094: 1092: 1090: 1087: 1086: 1083: 1081: 1079: 1076: 1075: 1072: 1070: 1068: 1065: 1064: 1061: 1059: 1057: 1054: 1053: 1050: 1048: 1046: 1043: 1042: 1039: 1037: 1034: 1033: 1030: 1028: 1026: 1023: 1022: 1019: 1017: 1015: 1012: 1011: 1008: 1006: 1004: 1001: 1000: 997: 995: 993: 990: 989: 986: 984: 982: 979: 978: 975: 973: 971: 968: 967: 964: 962: 960: 957: 956: 953: 951: 949: 946: 945: 942: 940: 938: 935: 934: 931: 929: 927: 924: 923: 920: 918: 916: 913: 912: 909: 907: 905: 902: 901: 898: 896: 894: 891: 890: 887: 885: 883: 880: 879: 876: 874: 872: 869: 868: 865: 863: 861: 858: 857: 854: 852: 850: 847: 846: 843: 841: 839: 836: 835: 832: 830: 828: 825: 824: 821: 819: 817: 814: 813: 810: 808: 805: 804: 801: 799: 797: 794: 793: 790: 788: 786: 783: 782: 779: 777: 775: 772: 771: 768: 766: 764: 761: 760: 757: 755: 753: 750: 749: 747: 744: 742: 739: 738: 735: 733: 731: 728: 727: 725: 722: 720: 717: 716: 713: 711: 709: 706: 705: 703: 700: 698: 695: 694: 691: 689: 687: 684: 683: 681: 678: 676: 673: 672: 669: 667: 665: 662: 661: 659: 656: 654: 651: 650: 647: 645: 643: 640: 639: 637: 634: 632: 629: 628: 625: 623: 620: 619: 617: 614: 612: 609: 608: 605: 603: 601: 598: 597: 595: 592: 590: 587: 586: 583: 581: 579: 576: 575: 573: 570: 568: 565: 564: 561: 559: 557: 554: 553: 551: 548: 546: 543: 542: 539: 537: 535: 532: 531: 529: 526: 524: 521: 520: 518:| type = combo 517: 515: 513: 510: 509: 507: 504: 502: 499: 498: 495: 493: 491: 488: 487: 485: 482: 480: 477: 476: 473: 471: 468: 467: 465: 462: 460: 457: 456: 453: 451: 449: 446: 445: 443: 440: 438: 435: 434: 431: 429: 427: 424: 423: 421: 418: 416: 413: 412: 409: 407: 405: 402: 401: 399: 396: 394: 391: 390: 387: 385: 383: 380: 379: 377: 374: 372: 369: 368: 365: 363: 361: 358: 357: 355: 352: 350: 347: 346: 343: 341: 339: 336: 335: 333: 330: 328: 325: 324: 321: 319: 317: 314: 313: 310: 308: 306: 303: 301: 298: 297: 294: 292: 290: 287: 286: 283: 281: 279: 276: 275: 272: 270: 268: 265: 264: 261: 257: 256: 252: 251: 212: 191: 169: 129: 121: 115: 99: 93: 85: 79: 76: 75: 68: 56: 50: 42: 36: 33: 32: 25: 23: 19: 18: 10: 6: 4: 3: 2: 2644: 2630: 2625: 2619: 2614: 2608: 2603: 2597: 2592: 2586: 2581: 2575: 2570: 2564: 2557: 2554: 2548: 2546: 2541: 2539: 2538: 2532: 2527: 2523: 2521: 2518: 2516: 2515: 2509: 2504: 2498: 2493: 2487: 2482: 2476: 2471: 2465: 2460: 2454: 2449: 2445: 2440: 2430: 2419: 2416: 2410: 2408: 2403: 2401: 2400: 2396: 2394: 2391: 2389: 2388: 2381: 2376: 2370: 2365: 2359: 2354: 2350: 2345: 2338: 2333: 2329: 2324: 2317: 2312: 2308: 2303: 2296: 2291: 2287: 2282: 2276: 2271: 2265: 2260: 2256: 2251: 2244: 2239: 2235: 2230: 2224: 2219: 2213: 2208: 2202: 2197: 2191: 2186: 2182: 2177: 2171: 2166: 2162: 2157: 2150: 2145: 2139: 2134: 2130: 2125: 2119: 2114: 2108: 2103: 2097: 2092: 2086: 2081: 2075: 2070: 2064: 2059: 2053: 2048: 2042: 2037: 2033: 2028: 2021: 2016: 2010: 2005: 2001: 1996: 1990: 1985: 1976: 1973: 1967: 1962: 1958: 1956: 1953: 1951: 1950: 1943: 1938: 1930: 1927: 1921: 1916: 1912: 1910: 1907: 1905: 1904: 1896: 1893: 1885: 1882: 1874: 1871: 1863: 1860: 1853: 1848: 1844: 1842: 1839: 1837: 1836: 1828: 1825: 1773:HCI/bupropion 1561:among others, 1539: 1282: 1279: 1275: 1273: 1270: 1268: 1267: 1261: 1259: 1254: 1252: 1251: 1245: 1240: 1236: 1231: 1225: 1220: 1214: 1209: 1203: 1198: 1192: 1187: 1181: 1176: 1170: 1165: 1159: 1154: 1148: 1143: 1137: 1132: 1126: 1121: 1115: 1110: 1106:| DrugBank = 1104: 1099: 1093: 1088: 1082: 1077: 1071: 1066: 1060: 1055: 1049: 1044: 1040: 1035: 1029: 1024: 1018: 1013: 1007: 1002: 996: 991: 985: 980: 974: 969: 963: 958: 952: 947: 941: 936: 930: 925: 919: 914: 908: 903: 897: 892: 886: 881: 875: 870: 864: 859: 853: 848: 842: 837: 831: 826: 820: 815: 811: 806: 800: 795: 789: 784: 778: 773: 767: 762: 756: 751: 743: 740: 734: 729: 721: 718: 712: 707: 699: 696: 690: 685: 677: 674: 668: 663: 655: 652: 646: 641: 633: 630: 626: 621: 613: 610: 604: 599: 591: 588: 582: 577: 569: 566: 560: 555: 547: 544: 538: 533: 525: 522: 516: 511: 503: 500: 494: 489: 481: 478: 474: 469: 461: 458: 452: 447: 439: 436: 430: 425: 417: 414: 410:| width = 200 408: 403: 395: 392: 386: 381: 373: 370: 364: 359: 351: 348: 342: 337: 329: 326: 320: 315: 309: 307: 302: 300: 299: 293: 288: 282: 277: 271: 266: 258: 253: 241: 230: 220: 215: 213:151.202.20.36 206: 201: 197: 189: 177: 172: 163: 159: 143: 136: 126:Content added 118: 16: 1589:= Plodkowski 1568:] medication 1458:synergistic 1428:formulation, 1308:experimental 1227:| synonyms = 562:| class1 = ] 2267:==History== 1730:medications 1683:antagonist, 1474:Wallingford 1337:Umasankari; 1194:| ChEMBL = 244:Mobile edit 170:71.20.8.226 1770:Naltrexone 1737:been shown 1621:, St Jeor 1543:Naltrexone 1501:naltrexone 1326:A.; Nguyen 1313:for ] in ] 1290:naltrexone 1172:| ChEBI = 96:Revision 2 53:Revision 1 1788:Adherence 1663:56625956 1547:bupropion 1497:Bupropion 1443:]. Both 1394:1069–1081 1351:Diane L.; 1311:treatment 1294:(proposed 1286:Bupropion 311:{{Drugbox 304:{{Drugbox 1751:vauthors 1739:to have 1701:<ref 1670:contains 1602:Sundaram 1587:vauthors 1513:decrease 1504:interact 1468:Sinnayah 1454:to have 1452:expected 1402:19364254 1333:Sundaram 432:| alt = 141:Wikitext 2434:Reflist 2423:reflist 1780:journal 1723:<ref 1647:1069–81 1533:Obesity 1529:journal 1486:Crowley 1362:Sachiko 1323:Raymond 263:Line 1: 260:Line 1: 183:clarity 1794:volume 1709:label" 1680:opioid 1627:volume 1609:Nguyen 1595:Nguyen 1519:intake 1464:author 1460:effect 1374:volume 1344:Loida; 1340:Nguyen 1330:Quang; 1319:author 134:Visual 82:Page 2 72:Page 2 39:Page 1 29:Page 1 1946:/> 1812:751–9 1806:pages 1764:title 1728:Both 1719:taken 1712:/> 1659:s2cid 1643:pages 1635:issue 1557:brand 1493:title 1480:Evans 1445:drugs 1390:pages 1382:issue 1297:trade 1816:date 1786:and 1741:some 1651:date 1616:Chau 1574:] in 1525:mice 1516:food 1499:and 1416:> 1398:pmid 1370:2009 1366:year 1357:Jeor 1347:Chau 1292:''' 240:Tags 219:talk 205:undo 200:edit 176:talk 162:edit 2110:* ] 1755:Tek 1734:has 1717:is 1706:FDA 1686:and 1570:for 1563:is 1549:''' 1541:''' 1440:and 1433:is 1414:ref 1303:is 1284:''' 2436:}} 2432:{{ 2425:}} 2421:{{ 1818:= 1814:| 1800:10 1782:= 1778:| 1753:= 1721:]. 1715:It 1699:]. 1692:an 1689:], 1677:an 1667:It 1661:= 1653:= 1649:| 1645:= 1641:| 1637:= 1633:| 1631:10 1629:= 1619:DL 1614:, 1607:, 1600:, 1593:, 1591:RA 1531:= 1527:| 1522:in 1510:to 1495:= 1491:| 1489:MA 1483:A, 1477:N, 1471:P, 1466:= 1449:is 1431:it 1419:in 1400:= 1392:= 1388:| 1384:= 1380:| 1378:10 1376:= 1372:| 1368:= 1353:St 1342:, 1335:, 1328:, 1305:an 1263:}} 1256:}} 242:: 231:: 2632:] 2621:] 2610:] 2599:] 2588:] 2577:] 2566:] 2559:] 2550:] 2543:] 1809:= 1803:| 1797:= 1791:| 1767:= 1761:| 1758:C 1744:] 1695:] 1674:, 1672:] 1639:6 1623:S 1612:L 1605:U 1598:Q 1578:] 1565:a 1551:, 1545:/ 1456:a 1437:] 1422:a 1412:/ 1408:] 1386:6 1359:, 1355:. 1349:, 1315:s 1301:) 1288:/ 221:) 217:( 178:) 174:(

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