Buy Contrave 8/90

Naltrexone/bupropion, sold under the brand name Contrave among others, is a fixed-dose combination medication for the management of chronic obesity in adults in combination with a reduced-calorie diet and increased physical activity. It contains naltrexone, an opioid antagonist, and bupropion, an aminoketone atypical antidepressant.^[4] It is taken by mouth. 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.^[7]

In September 2014, a sustained release formulation of the drug was approved for marketing in the United States under the brand name Contrave.^[8][9] The combination was subsequently approved in the European Union in the spring of 2015, where it is sold under the name Mysimba.^[5][10] It was approved in Canada under the Contrave brand name in 2018.^[11]

Naltrexone/bupropion is indicated, as an adjunct to a reduced-calorie diet and increased physical activity, as anti-obesity medication for the management of weight in adults with an initial body mass index (BMI) of:^[4][5]

• 30 kg/m² (obese), or^[4][5]
• 27 kg/m² to < 30 kg/m², (overweight) in the presence of one or more weight-related comorbidities, like type 2 diabetes, dyslipidaemia, or controlled high blood pressure^[4][5]

Each Contrave tablet contains 8 mg naltrexone and 90 mg bupropion.^[12] 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.^[12]

According to the U.S. Food and Drug Administration (FDA), naltrexone/bupropion is contraindicated in patients who have/are:^[4]

• History of seizures
• History of an eating disorder such as bulimia nervosa or anorexia nervosa
• Taking opioids, or are in opiate withdrawal.
• Taken monoamine oxidase inhibitors in the last 14 days
• Pregnant
• Abruptly stopped use of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs

The FDA has issued a boxed warning regarding an increased risk for suicidal thoughts and behavior in children, adolescents, and young adults under the age of 25.^[4] This is attributed to the bupropion component, as the FDA requires all antidepressants to include that boxed warning on medication package inserts.^[13]

The safety and effectiveness of Naltrexone/bupropion in children under the age of 18 has not been studied.^[4]

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

• Bupropion is a reuptake inhibitor of both norepinephrine and dopamine, 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.^{[medical citation needed]}
• Naltrexone is a pure opioid antagonist, which further augments bupropion’s activation of the POMC.^[14]

Combined, naltrexone/bupropion affects the reward pathway which results in reduced food cravings.^[15] 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.^[16]

Orexigen submitted a New Drug Application (NDA) for the combination to the FDA in March 2010.^[17] 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 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.^[18] 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.^[19] It was ultimately approved in the United States in 2014.^[9] 

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