In September 2014, asustained release formulation of the drug was approved for marketing in the United States under the brand nameContrave.[7][8] The combination was subsequently approved in theEuropean Union in the spring of 2015, where it is sold under the name Mysimba.[4][9] It was approved in Canada under the Contrave brand name in 2018.[10]
Naltrexone/bupropion is indicated, as an adjunct to a reduced-calorie diet and increased physical activity, asanti-obesity medication for the management of weight in adults with an initialbody mass index (BMI) of:[3][4]
Each Contrave tablet contains 8 mg naltrexone and 90 mg bupropion.[11] Once full dosing is reached (after 4 weeks of administration), the total dosage of Contrave for treating overweight or obesity is two tablets twice daily or 32 mg naltrexone and 360 mg bupropion per day.[11]
The FDA has issued aboxed warning regarding an increased risk for suicidal thoughts and behavior in children, adolescents, and young adults under the age of 25.[3] This is attributed to the bupropion component, as the FDA requires allantidepressants to include that boxed warning onmedication package inserts.[12]
The safety and effectiveness of Naltrexone/bupropion in children under the age of 18 has not been studied.[3]
Naltrexone is a pure opioid antagonist, which further augments bupropion's activation of the POMC.[13]
Combined, naltrexone/bupropion affects the reward pathway which results in reduced food cravings.[14] In 2009,Monash University physiologist Michael Cowley was awarded one ofAustralia'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.[15]
Orexigen submitted aNew Drug Application (NDA) for the combination to the FDA in March 2010.[16] Having paid a fee under thePrescription Drug User Fee Act, 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.[17] 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.[18] It was ultimately approved in the United States in 2014.[8]
In May 2015, Orexigen prematurely ended the trial that was intended to test whether naltrexone/bupropion increased the risk ofmajor adverse cardiovascular events in obese patients with cardiovascular disease because an independent panel of experts said that the drug maker “inappropriately” compromised the trial by prematurely 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.[21] 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.[22]
In 2018, Orexigen sold its assets, including Contrave, to Nalpropion Pharmaceuticals.[23][24]
The sustained-release formulation, Contrave, is marketed byTakeda under license from the combination medication's developer, Orexigen Therapeutics.[8] As of 2015, Orexigen received 20% of net sales from Takeda.[25]
^abcde"Mysimba EPAR".European Medicines Agency (EMA). 17 September 2018.Archived from the original on 22 October 2020. Retrieved5 August 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^Plodkowski RA, Nguyen Q, Sundaram U, Nguyen L, Chau DL, St Jeor S (April 2009). "Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity".Expert Opinion on Pharmacotherapy.10 (6):1069–81.doi:10.1517/14656560902775750.PMID19364254.S2CID56625956.
N
Y (what is this?) (verify)