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Bupropion and naltrexone.svg
Skeletal structures of bupropion (top) and naltrexone (bottom)
Combination of
NaltrexoneOpioid receptor antagonist
BupropionNorepinephrine-dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist
Trade namesContrave, Mysimba
Clinical data
Main usesObesity[1]
Side effectsNausea, constipation, dizziness, trouble sleeping, dry mouth, headache[1]
  • US: X (Contraindicated)
Routes of
By mouth
External links
Legal status

Naltrexone/bupropion, sold under the brand name Contrave among others, is a combination medication used to treat obesity together with diet and exercise.[1] Up to 30% more people loss at least 5% body weight with use.[4] Such use; however, is not recommended in the United Kingdom.[5] It is taken by mouth.[1]

Common side effects include nausea, constipation, dizziness, trouble sleeping, dry mouth, and headache.[1] Other side effects may include suicide, psychosis, seizures, high blood pressure, and liver problems.[1] Use during pregnancy is not recommended.[1] It contains naltrexone, an opioid antagonist, and bupropion, an aminoketone antidepressant.[3]

The combination was approved for medical use in the United States in 2014, Europe in 2015, and Canada in 2018.[6][2][7] In the United States it costs 330 USD per month as of 2021 while in Canada it is about 350 CAD as of 2022.[8][4] This amount in the United Kingdom costs about £78.[5]

Medical uses

Naltrexone/bupropion is indicated, as an adjunct to a reduced-calorie diet and increased physical activity, for the management of weight in adults with an initial body mass index (BMI) of:[3][2]

Both medications have individually shown some evidence of effectiveness in weight loss, and the combination has been shown to have some synergistic effects on weight.[9]

Available forms

Each tablet contains 8 mg naltrexone and 90 mg bupropion.[10] Once full dosing is reached (after 4 weeks of administration), the total dosage is two tablets twice daily or 32 mg naltrexone and 360 mg bupropion per day.[10]


The manufacturer recommends against its use in people that have/are:[3]

Side effects

The Food and Drug Administration (FDA) has put a boxed warning onto this medicine because it may affect mood and increase the likelihood of suicidal thoughts in people under 25 years old.[3] This is attributed to the bupropion component, as antidepressants have been associated with increased risk of suicidal thoughts, but not suicide, and only in people younger than 25.[3]

The safety and effectiveness in children under the age of 18 has not been studied.[3]

Mechanism of action

Naltrexone/bupropion versus placebo on the brain's reactivity to food cues

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

Combined, naltrexone/bupropion has an effect on the reward pathway that results in reduced food craving.[12] In 2009, Monash University physiologist Michael Cowley was awarded one of Australia'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.[13]


Orexigen submitted a New Drug Application (NDA) for this drug combination to the U.S. Food and Drug Administration (FDA) on 31 March 2010.[14] Having paid a fee under the Prescription Drug User Fee Act, Orexigen was given a deadline for the FDA to approve or reject the drug of 31 January 2011. 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.[15] 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.[16] It was ultimately approved in the United States in the fall of 2014.[17]

In December 2014, the EU's Committee for Medicinal Products for Human Use (CHMP) endorsed the combination for licensure as an obesity medication when used alongside diet and exercise.[18] Approval was granted in late March 2015.[19]

In May 2015, Orexigen ended a safety study of its diet drug earlier than planned, because an independent panel of experts says the drug maker “inappropriately” compromised the trial by prematurely releasing interim data. The early data release reported a reduction in heart attacks that was no longer observed when a more complete view of the data was analyzed.[20]

In 2018, Orexigen sold its assets, including Contrave, to Nalpropion Pharmaceuticals.[21][22]

Society and culture


The sustained-release formulation, Contrave, is marketed by Takeda under license from the combination medication's developer, Orexigen Therapeutics.[17] As of 2015, Orexigen received 20% of net sales from Takeda.[23]

At the time of its approval by FDA, Wells Fargo analyst Matthew Andrews estimated that Contrave's U.S. sales would reach approximately US$200,000,000 in 2016, exceeding that of the dominant alternative obesity medications lorcaserin and phentermine/topiramate.[24] Despite being initially impeded by technical issues, the growth in filled prescriptions in the first months after approval was very rapid — substantially exceeding the equivalent early uptake of either of the two alternative medications just cited.[25] The first quarter of sales for Contrave (Q1 2015) showed net sales of US$11,500,000.[23]

Despite having been approved for use in Europe in March 2015, sales of Contrave have not begun[when?] as Orexigen has not yet found a marketing partner.[23][needs update]

See also


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Bupropion / naltrexone (Contrave) Use During Pregnancy". Archived from the original on 18 January 2021. Retrieved 11 November 2021.
  2. 2.0 2.1 2.2 2.3 2.4 "Mysimba EPAR". European Medicines Agency (EMA). Archived from the original on 22 October 2020. Retrieved 5 August 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 "Contrave Extended-Release- naltrexone hydrochloride and bupropion hydrochloride tablet, extended release". DailyMed. 26 April 2019. Archived from the original on 4 June 2020. Retrieved 5 August 2020.
  4. 4.0 4.1 Ton, Joey (2 May 2022). "#314 Weight to Go: Naltrexone/bupropion for weight loss". CFPCLearn. Archived from the original on 1 July 2023. Retrieved 14 June 2023.
  5. 5.0 5.1 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 99. ISBN 978-0857114105.
  6. "Naltrexone And Bupropion Monograph for Professionals". Archived from the original on 25 January 2021. Retrieved 11 November 2021.
  7. "Regulatory Decision Summary - Contrave - Health Canada". Health Canada. 13 February 2018. Archived from the original on 4 December 2020. Retrieved 5 September 2021.
  8. "Contrave Prices, Coupons & Patient Assistance Programs". Archived from the original on 18 April 2021. Retrieved 11 November 2021.
  9. Tek C (2016). "Naltrexone HCI/bupropion HCI for chronic weight management in obese adults: patient selection and perspectives". Patient Preference and Adherence. 10: 751–9. doi:10.2147/PPA.S84778. PMC 4862388. PMID 27217728.
  10. 10.0 10.1 "Archive copy" (PDF). Archived (PDF) from the original on 2021-10-02. Retrieved 2021-10-24.{{cite web}}: CS1 maint: archived copy as title (link)
  11. Greenway FL, Whitehouse MJ, Guttadauria M, Anderson JW, Atkinson RL, Fujioka K, et al. (January 2009). "Rational design of a combination medication for the treatment of obesity". Obesity. 17 (1): 30–9. doi:10.1038/oby.2008.461. PMID 18997675. S2CID 24856014.
  12. Apovian CM, Aronne L, Rubino D, Still C, Wyatt H, Burns C, et al. (May 2013). "A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II)". Obesity. 21 (5): 935–43. doi:10.1002/oby.20309. PMC 3739931. PMID 23408728.
  13. "Obesity expert named Life Scientist of the Year". Monash University. 29 October 2009. Archived from the original on 2 November 2009.
  14. "Orexigen Therapeutics Submits Contrave New Drug Application to FDA for the Treatment of Obesity". Archived from the original on 2016-12-30. Retrieved 2021-10-24.
  15. "Press Release". Orexigen Therapeutics, Inc. 2010-12-07. Retrieved 2016-12-29.{{cite web}}: CS1 maint: url-status (link)
  16. Contrave Archived 2016-12-30 at the Wayback Machine,
  17. 17.0 17.1 "FDA approves weight-management drug Contrave" (Press release). FDA. 10 September 2014. Archived from the original on 17 February 2017. Retrieved 24 October 2021.
  18. "Orexigen's weight-loss drug gets thumbs-up from CHMP". FiercePharma. 2014-12-19. Archived from the original on 2016-12-30. Retrieved 2016-12-29.
  19. Orexigen Therapeutics, Inc. (March 26, 2015). "Orexigen's Mysimba Approved in Europe for the Treatment of Obesity". Yahoo! Finance. PR Newswire. Archived from the original on 31 March 2015. Retrieved 28 March 2015.
  20. Silverman E (2015-05-12). "Orexigen Study for Diet Drug Ends Over Premature Data Disclosure". WSJ. Archived from the original on 2016-12-30. Retrieved 2016-12-29.
  21. "Orexigen, seller of weight-loss drug Contrave, agrees to sale for $75 million". San Diego Union-Tribune. 23 April 2018. Archived from the original on 13 October 2018. Retrieved 5 August 2020.
  22. "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". Nalpropion Pharmaceuticals. 19 December 2018. Archived from the original on 28 October 2021. Retrieved 5 August 2020 – via GlobeNewswire.
  23. 23.0 23.1 23.2 Osborne S (May 8, 2015). "Orexigen Posts Loss - Revenue Will Be The Story". Seeking Alpha (blog). Archived from the original on May 10, 2015. Retrieved May 9, 2015.
  24. Grover N (September 10, 2014). "Reuters More: Reuters Health Long-awaited Diet Pill Gets U.S. Approval Reuters". Business Insider. Reuters. Archived from the original on April 2, 2015. Retrieved March 28, 2015.
  25. Osborne S (December 12, 2014). "Contrave Sales Continue To Impress". Seeking Alpha (blog). Archived from the original on December 29, 2014. Retrieved March 28, 2015.

External links