STEPS

New Drug Reviews

Naltrexone/Bupropion (Contrave) for Weight Loss

JESSICA Early, MD, and JEAN SUZIN WHITTEN, Physician, Tufts University Family Medicine Residency at Cambridge Health Alliance, Malden, Massachusetts

Am Fam Dr.. 2015 April fifteen;91(8):554-556.

Naltrexone/bupropion (Contrave) combines an opioid receptor antagonist (naltrexone) with a dopamine and norepinephrine reuptake inhibitor (bupropion) in an extended-release tablet. It is labeled as an adjunct to increased physical action and a reduced-calorie nutrition for chronic weight management in adults who have a body mass index (BMI) of at least xxx kg per 1000ii or who have a BMI of at least 27 kg per g2 with one or more than weight-related comorbidities such as type 2 diabetes mellitus, hyperlipidemia, or hypertension.

Drug Dosage Dose form Cost*

Naltrexone/bupropion (Contrave)

viii/90 mg per day, increasing over 4 weeks to 16/180 mg twice daily

8/90-mg extended-release tablet

$212 for iv tablets per day

Safe

Safety concerns with bupropion include low, hypertension, and hazard of seizures, whereas acute opioid withdrawal and opioid overuse have been associated with naltrexone.one Naltrexone/bupropion is labeled every bit increasing the chance of low and suicidal behavior, based on studies of bupropion lone that showed an increase in the incidence of these events. All the same, clinical trials of the combination compared with placebo found no increase in depression and no increment in suicidality.2–four Naltrexone/bupropion should not be given to children or adolescents. Considering it may raise blood force per unit area and eye rate, it should not be used in patients with uncontrolled high blood pressure. It also should non be prescribed to patients with a known seizure disorder or those already taking opioids. The total daily dosage of naltrexone/bupropion should not exceed two tablets twice a mean solar day.1

Although one of the goals of weight loss is to decrease the hazard of cardiovascular outcomes, patients with agile cardiovascular disease, including significant center failure, history of myocardial infarction, angina, or stroke, were excluded from premarketing studies. A large cardiovascular outcomes study that includes these patients is now ongoing. Bupropion is metabolized in the liver and its utilize may increase serum levels of some antidepressants, antipsychotics, beta blockers, and antiarrhythmics. Lower doses of these medications may exist needed with concomitant utilize.1

Naltrexone/bupropion is pregnancy category X. Both components are excreted in breast milk and the medication should not be taken past breastfeeding mothers.one

TOLERABILITY

Gastrointestinal symptoms are common with naltrexone/bupropion. Upwards to 1 in three patients will written report nausea and nineteen% will experience constipation, particularly early in handling. Headache, dizziness, and slumber disorders are too mutual.1 In premarketing studies, about 20% of patients discontinued treatment because of adverse effects.2–5

EFFECTIVENESS

Naltrexone/bupropion has been evaluated in three studies that enrolled more than 4,000 overweight or obese patients with hyperlipidemia or hypertension, and in i written report of 505 patients with diabetes. In all studies, naltrexone/bupropion combined with a nutrition and exercise program for ane yr resulted in greater weight loss than placebo combined with a diet and exercise plan.two–5 About four patients need to be treated with naltrexone/bupropion instead of placebo for one additional patient to achieve at to the lowest degree a five% weight loss (number needed to treat = 4).2–4 Clinically significant weight loss was likewise achieved with placebo plus an intensive program of behavior modification, which supports the implementation of intensive interventions when these resources exist.four In settings where these resources are not bachelor, naltrexone/bupropion combined with less intensive lifestyle interventions may also achieve clinically significant weight loss for obese patients.2,3

Naltrexone/bupropion has not been compared with other pharmacologic approaches. It is unknown if weight gain occurs later on stopping the medication, and patient-oriented outcomes such as the development of osteoarthritis, diabetes, hypertension, cardiovascular affliction, and mortality take not been studied.

PRICE

Naltrexone/bupropion costs approximately $212 for a i-month supply.

SIMPLICITY

The dosing of naltrexone/bupropion must exist titrated. In week one, patients should take one 8/90-mg tablet one time a day in the morning with a depression-fatty meal. In calendar week 2, they should increase the daily dosage to one tablet in the morning and one tablet in the evening. During week 3, patients should increase the daily dosage to ii tablets in the morn and one tablet in the evening, and in week four patients will achieve the maximum recommended dosage of two tablets twice a day.one Patients with moderate to astringent renal impairment should exist limited to 1 tablet twice daily, and patients with moderate hepatic impairment should be limited to one tablet daily.1 If patients exercise not lose v% of their baseline body weight after 12 weeks, further handling is unlikely to be beneficial and therapy should be discontinued.1 If patients achieve clinically significant weight loss later 12 weeks, therapy should be continued for up to 1 year. Naltrexone/bupropion has not been studied beyond 56 weeks.2–five

Bottom Line

Naltrexone/bupropion produces clinically significant weight loss when combined with a diet and exercise programme. It decreases body weight in patients with diabetes, but its effect on diabetic outcomes is not known. A pregnant proportion of patients will feel adverse furnishings. It should not be prescribed for patients with preexisting eye disease until the effects are known. If prescribed, naltrexone/bupropion should exist used with a nutrition and exercise plan and should be discontinued if at to the lowest degree a 5% weight loss is not achieved inside three months.

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Accost correspondence to Jessica Early, MD, at jearly@challiance.org. Reprints are not bachelor from the authors.

Author disclosure: No relevant financial affiliations.

REFERENCES

evidence all references

one. Contrave (naltrexone hydrochloride and bupropion hydrochloride) tablet, movie coated, extended release. DailyMed. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ed2da3a6-0614-4bea-8e82-962cbaae6428. Accessed Dec v, 2014. ...

2. Greenway FL, Fujioka K, Plodkowski RA, et al.; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase iii trial [published corrections announced in Lancet. 2010;376(9750):1392, and Lancet. 2010;376(9741):594]. Lancet. 2010;376(9741):595–605.

three. Apovian CM, Aronne Fifty, Rubino D, et al.; COR-2 Report Group. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related run a risk factors (COR-II). Obesity (Silver Bound). 2013;21(five):935–943.

4. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy equally an adjunct to beliefs modification: the COR-BMOD trial. Obesity (Silvery Spring). 2011;19(1):110–120.

five. Hollander P, Gupta AK, Plodkowski R, et al.; COR-Diabetes Study Group. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes [published correction appears in Diabetes Intendance. 2014;37(2):587]. Diabetes Care. 2013;36(12):4022–4029.

STEPS new drug reviews encompass Safety, Tolerability, Effectiveness, Price, and Simplicity. Each contained review is provided by authors who have no financial association with the drug manufacturer.

This serial is coordinated by Allen F. Shaughnessy, PharmD, MMedEd, Contributing Editor.

A collection of STEPS published in AFP is bachelor at https://www.aafp.org/afp/steps.

Copyright © 2015 by the American Academy of Family Physicians.
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