Open Access Articles- Top Results for naltrexone
Journal of Alcoholism and Drug DependenceVariation in Mu-Opioid Receptor Gene (OPRM1) as a Moderator of Naltrexone Treatment to Reduce Heavy Drinking in a High Functioning Cohort
Medicinal chemistryOpioid Receptors and Ligands: Targets for Cancer Imaging and Therapy
Clinical & Experimental PharmacologyThe Occurrence of Spontaneous Lymphomas but Not Adenomas or Sarcomas in Rats Treated With Sustained Release Naltrexone
Clinical & Experimental PharmacologyInternational Expansion of the Use of Pharmacotherapies for the Treatment of Opioid Dependence
|Bupropion||Norepinephrine reuptake inhibitor/releasing agent and nicotinic acetylcholine receptor antagonist|
|Naltrexone||opioid receptor antagonist|
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Bupropion/naltrexone is a combination drug treatment for obesity. 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.
In September of 2014, a sustained release formulation of the drug was approved for marketing in the United States under the brand name Contrave. The combination was subsequently approved in the European Union in the spring of 2015, where it will be sold under the name Mysimba.
Takeda recommends that Contrave should not be used in anyone who falls into any of the categories below:
• 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
• Abrupt termination of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
The FDA has put a boxed warning onto this medicine 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.
Safety and effectiveness in children under the age of 18 has not been studied.
Mechanism of action
Individually, bupropion and naltrexone each target pathways in the central nervous system that influence food intake. Bupropion is a reuptake inhibitor and releasing agent of norepinephrine and a nicotinic acetylcholine receptor antagonist, and it activates proopiomelanocortin (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 bupropion's activation of the POMC. Bupropion/naltrexone has an effect on the reward pathway that results in reduced food craving. 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.
Orexigen submitted a New Drug Application (NDA) for this drug combination to the FDA On 31 March 2010. 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. 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. It was ultimately approved in the United States in the fall of 2014.
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. Approval was granted in late March of 2015.
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. 
Society and culture
The sustained-release formulation, Contrave, is marketed by Takeda under license from the combination medication's developer, Orexigen Therapeutics. As of 2015, Orexigen received 20% of net sales from Takeda.
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. 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. The first quarter of sales for Contrave (Q1 2015) showed net sales of US$11.5 million.
Despite having been approved for use in Europe in March 2015, sales of Contrave have not begun as Orexigen has not yet found a marketing partner.
- "FDA approves weight-management drug Contrave" (Press release). FDA. 10 September 2014.
- 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. PMID 19364254. doi:10.1517/14656560902775750.
- Sinnayah P, Wallingford N, Evans A, Crowley MA (2007). "Bupropion and naltrexone interact synergistically to decrease food intake in mice". Obesity 15 (9): A179.
- 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.
- "Contrave Prescribing Information". Takeda. Retrieved 2 November 2014.
- 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.
- 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.
- "Obesity expert named Life Scientist of the Year". Monash University. 29 October 2009. Archived from the original on 2 November 2009.
- Orexigen(R) Therapeutics Submits Contrave(R) New Drug Application to FDA for the Treatment of Obesity
- 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.
- Osborne, Spencer (May 8, 2015). "Orexigen Posts Loss - Revenue Will Be The Story". Seeking Alpha (blog). Retrieved May 9, 2015.
- Grover, Natalie (September 10, 2014). "Reuters More: Reuters Health Long-awaited Diet Pill Gets U.S. Approval Reuters". Business Insider. Reuters. Retrieved March 28, 2015.
- Osborne, Spencer (December 12, 2014). "Contrave Sales Continue To Impress". Seeking Alpha (blog). Retrieved March 28, 2015.