STEPS

New Drug Reviews

Naltrexone/Bupropion (Contrave) for Weight Loss

JESSICA EARLY, Dr., and JEAN SUZIN WHITTEN, MD, Tufts University Family Medicine Residency at Cambridge Health Alliance, Malden, Massachusetts

Am Fam Physician. 2015 Apr 15;91(8):554-556.

Naltrexone/bupropion (Contrave) combines an opioid receptor adversary (naltrexone) with a dopamine and norepinephrine reuptake inhibitor (bupropion) in an extended-release tablet. Information technology is labeled every bit an adjunct to increased physical activity and a reduced-calorie nutrition for chronic weight management in adults who have a body mass alphabetize (BMI) of at to the lowest degree 30 kg per m2 or who have a BMI of at least 27 kg per chiliad2 with one or more weight-related comorbidities such as type 2 diabetes mellitus, hyperlipidemia, or hypertension.

Drug Dosage Dose course Toll*

Naltrexone/bupropion (Contrave)

eight/90 mg per twenty-four hours, increasing over four weeks to 16/180 mg twice daily

8/ninety-mg extended-release tablet

$212 for iv tablets per solar day

Condom

Prophylactic concerns with bupropion include low, hypertension, and risk of seizures, whereas acute opioid withdrawal and opioid overuse take been associated with naltrexone.1 Naltrexone/bupropion is labeled as increasing the hazard of low and suicidal behavior, based on studies of bupropion alone that showed an increase in the incidence of these events. Even so, clinical trials of the combination compared with placebo constitute no increase in low and no increment in suicidality.ii–4 Naltrexone/bupropion should not be given to children or adolescents. Considering it may heighten blood pressure and eye rate, it should non be used in patients with uncontrolled high claret pressure. Information technology also should not be prescribed to patients with a known seizure disorder or those already taking opioids. The full daily dosage of naltrexone/bupropion should not exceed ii tablets twice a twenty-four hours.one

Although i of the goals of weight loss is to decrease the risk of cardiovascular outcomes, patients with active cardiovascular disease, including significant heart failure, history of myocardial infarction, angina, or stroke, were excluded from premarketing studies. A big cardiovascular outcomes study that includes these patients is now ongoing. Bupropion is metabolized in the liver and its utilise may increase serum levels of some antidepressants, antipsychotics, beta blockers, and antiarrhythmics. Lower doses of these medications may be needed with concomitant use.ane

Naltrexone/bupropion is pregnancy category Ten. Both components are excreted in breast milk and the medication should non be taken by breastfeeding mothers.1

TOLERABILITY

Gastrointestinal symptoms are common with naltrexone/bupropion. Upward to i in 3 patients will report nausea and xix% will experience constipation, peculiarly early in treatment. Headache, dizziness, and sleep disorders are besides common.1 In premarketing studies, about twenty% of patients discontinued treatment because of adverse effects.two–5

EFFECTIVENESS

Naltrexone/bupropion has been evaluated in 3 studies that enrolled more than 4,000 overweight or obese patients with hyperlipidemia or hypertension, and in one written report of 505 patients with diabetes. In all studies, naltrexone/bupropion combined with a diet and exercise programme for one year resulted in greater weight loss than placebo combined with a diet and practice program.2–5 About four patients demand to be treated with naltrexone/bupropion instead of placebo for 1 additional patient to achieve at to the lowest degree a 5% weight loss (number needed to treat = 4).2–four Clinically significant weight loss was also accomplished with placebo plus an intensive program of beliefs modification, which supports the implementation of intensive interventions when these resources exist.4 In settings where these resource are not available, 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 after stopping the medication, and patient-oriented outcomes such as the evolution of osteoarthritis, diabetes, hypertension, cardiovascular disease, and mortality take not been studied.

PRICE

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

SIMPLICITY

The dosing of naltrexone/bupropion must be titrated. In week 1, patients should take i 8/90-mg tablet once a day in the morning with a low-fatty meal. In week ii, they should increase the daily dosage to 1 tablet in the morning and one tablet in the evening. During week 3, patients should increment the daily dosage to two tablets in the morning and one tablet in the evening, and in calendar week 4 patients will reach the maximum recommended dosage of two tablets twice a day.1 Patients with moderate to severe renal impairment should be limited to i tablet twice daily, and patients with moderate hepatic harm should be express to i tablet daily.1 If patients practice not lose 5% of their baseline body weight subsequently 12 weeks, further treatment is unlikely to be benign and therapy should be discontinued.1 If patients reach clinically significant weight loss after 12 weeks, therapy should exist connected for upwardly to ane year. Naltrexone/bupropion has not been studied beyond 56 weeks.2–5

Bottom Line

Naltrexone/bupropion produces clinically significant weight loss when combined with a diet and practice plan. It decreases body weight in patients with diabetes, merely its effect on diabetic outcomes is non known. A significant proportion of patients volition experience agin effects. It should not exist prescribed for patients with preexisting heart disease until the furnishings are known. If prescribed, naltrexone/bupropion should be used with a diet and exercise programme and should exist discontinued if at least a 5% weight loss is not achieved inside three months.

To see the full article, log in or purchase access.

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

Author disclosure: No relevant fiscal affiliations.

REFERENCES

show all references

1. Contrave (naltrexone hydrochloride and bupropion hydrochloride) tablet, film coated, extended release. DailyMed. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ed2da3a6-0614-4bea-8e82-962cbaae6428. Accessed December 5, 2014. ...

2. Greenway FL, Fujioka K, Plodkowski RA, et al.; COR-I Written report 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 appear in Lancet. 2010;376(9750):1392, and Lancet. 2010;376(9741):594]. Lancet. 2010;376(9741):595–605.

3. Apovian CM, Aronne L, Rubino D, et al.; COR-Two Report Grouping. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-Two). Obesity (Silver Bound). 2013;21(5):935–943.

4. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an offshoot to behavior modification: the COR-BMOD trial. Obesity (Silver Leap). 2011;19(one):110–120.

5. Hollander P, Gupta AK, Plodkowski R, et al.; COR-Diabetes Report 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 Care. 2014;37(2):587]. Diabetes Care. 2013;36(12):4022–4029.

STEPS new drug reviews cover Prophylactic, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial clan with the drug manufacturer.

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

A collection of STEPS published in AFP is available at https://world wide web.aafp.org/afp/steps.

Copyright © 2015 by the American Academy of Family unit Physicians.
This content is owned by the AAFP. A person viewing it online may make 1 printout of the material and may utilize that printout simply for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Well-nigh RECENT ISSUE

Mar 2022

Access the latest outcome of American Family Physician

Read the Result


E-mail Alerts

Don't miss a single issue. Sign up for the gratuitous AFP email table of contents.

Sign Up Now