Bupropion/naltrexone

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Bupropion/naltrexone
Combination of
Bupropion norepinephrine/dopamine reuptake inhibitor
Naltrexone opioid receptor antagonist
Clinical data
Trade names Contrave
  • X
  • US: Rx-only[1]
Identifiers
 YesY
 YesY (what is this?)  (verify)

Bupropion/naltrexone is a combination drug treatment for obesity.[1][2] It combines bupropion and naltrexone. Both drugs have individually shown some evidence of effectiveness in weight loss, and the combination is expected to have a synergistic effect.[3]

In September of 2014, a sustained release formulation of the drug was approved for marketing in the United States under the brand name Contrave.[1] It is marketed by Takeda under license from the combination medication's developer, Orexigen Therapeutics.[1] The combination was subsequently approved in the European Union in the spring of 2015, where it will be sold under the name Mysimba.[4]

Mechanism of Action[edit]

Individually, bupropion and naltrexone each target pathways in the central nervous system that influence food intake. Bupropion is a reuptake inhibitor of both the neurotransmitters dopamine and norepinephrine, and it also activates pro-opiomelanocortin (POMC) neurons in the hypothalamus which give an effect downstream, resulting in loss of appetite and increased energy output. The POMC is regulated by endogenous opioids via opioid-mediated negative feedback. Naltrexone by contrast is a pure opioid antagonist, therefore further augmenting buprion's activation of the POMC.[5] Bupropion/Naltrexone also has an effect on the reward pathway that results in reduced food craving.[6] 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.[7]

Contraindications[edit]

Takeda recommends that Contrave should not be used in anyone who falls into any of the categories below:[8]
• History of seizures
• History of an eating disorder such as bulimia or anorexia
• Taking opioid pain medicines, taking medicines to stop opioid addiction, or are in opiate withdrawal
• Currently taking an MAOI or have taken an MAOI in the last 14 days
Pregnant
• Abrupt termination of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs

Adverse effects[edit]

The FDA has put a boxed warning onto this medicine on buproprion because it may affect mood and increase the likelihood of suicide. Although rare, signs of mood and behavioral changes should be reported to a doctor.[8]

Safety and effectiveness in children under the age of 18 has not been studied. [8]

History[edit]

Orexigen submitted a New Drug Application (NDA) for this drug combination to the FDA On 31 March 2010.[9] 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.[10] 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.[11] It was ultimately approved in the United States in the fall of 2014.[1]

In December of 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.[12] Approval was granted in late March of 2015.[4]

Society and culture[edit]

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 million in 2016, exceeding that of the dominant alternative obesity medications lorcaserin and phentermine/topiramate.[13] 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.[14] Both total filled prescriptions and market share continued to expand into March of 2015.[15]

References[edit]

  1. ^ a b c d e "FDA approves weight-management drug Contrave" (Press release). FDA. 10 September 2014. 
  2. ^ Plodkowski, Raymond A.; Nguyen, Quang; Sundaram, Umasankari; Nguyen, Loida; Chau, Diane L.; St. Jeor, Sachiko (2009). "Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity". Expert Opinion on Pharmacotherapy 10 (6): 1069–1081. doi:10.1517/14656560902775750. PMID 19364254. 
  3. ^ Sinnayah P, Wallingford N, Evans A, Crowley MA (2007). "Bupropion and naltrexone interact synergistically to decrease food intake in mice". Obesity 15 (9): A179. 
  4. ^ a b Orexigen Therapeutics, Inc. (March 26, 2015). "Orexigen's Mysimba™ Approved in Europe for the Treatment of Obesity". Yahoo! Finance. PR Newswire. Retrieved 28 March 2015. 
  5. ^ Greenway, Frank; Whitehouse, M.J; Guttadauria, Maria; Anderson, James (2008). "Rational Design of a Combination Medication for the Treatment of Obesity". Obesity 17: 30-39. 
  6. ^ Apovian, Caroline; Aronne, Louis; Rubino, Domenica; Still, Christopher (2013). "A randomized, Phase 3 Trial of Naltrexone SR/Bupropion SR on Weight and Obesity-related Risk Factors (COR-II)". Obesity 21: 935-943. 
  7. ^ "Obesity expert named Life Scientist of the Year". Monash University. 29 October 2009. Archived from the original on 2 November 2009. 
  8. ^ a b c "Contrave Prescribing Information". Takeda. Retrieved 2 November 2014. 
  9. ^ Orexigen(R) Therapeutics Submits Contrave(R) New Drug Application to FDA for the Treatment of Obesity
  10. ^ www.orexigen.com
  11. ^ [1]
  12. ^ Palmer, Eric (December 19, 2014). "Orexigen's weight-loss drug gets thumbs-up from CHMP Recommendation adds to critical mass building for big sales in the category". FiercePharma. 
  13. ^ Grover, Natalie (September 10, 2014). "Reuters More: Reuters Health Long-awaited Diet Pill Gets U.S. Approval Reuters". Business Insider. Reuters. Retrieved 28 March 2015. 
  14. ^ Osborne, Spencer (December 12, 2014). "Contrave Sales Continue To Impress". Seeking Alpha. Retrieved 28 March 2015. 
  15. ^ Osborne, Spencer (March 28, 2015). "Orexigen Gains Market Share With Contrave Again". Seeking Alpha. Retrieved 28 March 2015.