Obesity is a chronic disease2

Are you treating it as one?

“Health care providers should assess their own attitudes and beliefs regarding obesity
and consider how their attitudes and beliefs may influence care delivery.”
~Adapted from the 2020 Obesity Canadian Clinical Practice Guidelines3
Refer to complete guidelines for full recommendations.

CONTRAVE is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic
weight management in adults with an initial body mass index (BMI) of:
• 30 kg/m2 or greater (obese) or
• 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity
(e.g., controlled hypertension, type 2 diabetes mellitus, or dyslipidemia).
 An anti-obesity agent for
chronic weight management1

Naltrexone/bupropion combination is a recommended option, in conjunction with medical

nutrition therapy, physical activity, and psychological interventions, for individuals with a
BMI ≥30 kg/m2 or ≥27 kg/m2 with adiposity-related comorbidities.
~Adapted from the 2020 Obesity Canadian Clinical Practice Guidelines4
Refer to complete guidelines for full recommendations.

CONTRAVE is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic
weight management in adults with an initial body mass index (BMI) of:
• 30 kg/m2 or greater (obese) or
• 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity
(e.g., controlled hypertension, type 2 diabetes mellitus, or dyslipidemia).
A dual-component mechanism of action1*

Bupropion
Naltrexone
An opioid antagonist + A relatively weak inhibitor of the
neuronal reuptake of dopamine
and norepinephrine
= CONTRAVE

Non-clinical studies suggest that CONTRAVE has effects on two separate areas of
the brain involved in the regulation of food intake.
The exact neurochemical effects of CONTRAVE leading to weight loss are not fully understood.

Mesolimbic
Hypothalamus dopamine circuit
(appetite regulatory centre)
(reward system)

Adapted from the Product Monograph.

* Clinical significance is unknown.
CONTRAVE demonstrated significantly more weight loss vs. placebo
Mean change in body weight was -5.4% in the CONTRAVE 32 mg/360 mg group vs. -1.3% in the placebo group
(primary endpoint, ITT population).

COR-I: Mean change in weight over 56 weeks in the completer population 1*

4X more weight loss
with CONTRAVE
in the ITT population
(primary endpoint, LOCF)

-1.3% (1.4 kg)

placebo

-5.4% (5.5 kg)

CONTRAVE
(p<0.001)

50.1% of patients in the placebo

group and 49.2% of patients
in the CONTRAVE group
discontinued treatment.

ITT: intention to treat; LOCF: last observation carried forward.

Adapted from the Product Monograph.
* A phase 3, 56-week multicenter, double-blind, placebo-controlled study of patients with obesity (BMI ≥30 kg/m 2) or overweight (BMI ≥27 kg/m2) and at least one comorbidity (hypertension or dyslipidemia).
Patients were randomized to naltrexone (16–50 mg/day) and/or bupropion (300–400 mg/day) or placebo. Results presented are for the recommended daily dose of two 8 mg/90 mg tablets taken twice daily
for a total dose of 32 mg/360 mg. Treatment was initiated with a 3-week dose-escalation period followed by approximately 1 year of continued therapy. Treatment included a program consisting of instruction
to follow a reduced-calorie diet resulting in an approximate 500 kcal/day decrease in caloric intake, behavioural counselling, and increased physical activity. Co-primary endpoints were percent change from
baseline body weight and proportion of subjects achieving ≥5% total decreased body weight. Mean baseline weight for CONTRAVE/placebo: 99.8 kg (n=538)/99.5 kg (n=536). Other mean baseline values
for CONTRAVE/placebo: waist circumference (cm) 108.8/110.0; triglycerides (mmol/L) 1.3/1.3; HDL-C (mmol/L) 1.3/1.3; LDL-C (mmol/L) 3.1/3.1; systolic blood pressure (mmHg) 118.9/119.0; diastolic blood
pressure (mmHg) 77.1/77.3; heart rate (bpm) 72.1/71.8.
Demonstrated effect of CONTRAVE on cardiovascular and metabolic parameters
The effect of CONTRAVE on cardiovascular morbidity and mortality has not been established.

COR-I: Change from baseline to week 56 in patients overweight or with obesity, and without diabetes 1

BP: blood pressure; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol.
Adapted from the Product Monograph.
* Least square means, from all randomized subjects who had a baseline measurement and had at least one post baseline body weight measurement while on study drug. Based on LOCF with the last on drug
observation carried forward.
† Values are baseline median, median % change, and the Hodges-Lehmann estimate of the median treatment difference.
In conjunction with intensive BMOD counselling*
CONTRAVE demonstrated significantly more weight loss vs. placebo
Mean change in body weight was -8.1% in the CONTRAVE 32 mg/360 mg group vs. -4.9% in the
placebo group (primary endpoint, ITT population).

COR-BMOD: Mean change in weight over 56 weeks in the completer population 1†

Significantly more weight
loss with CONTRAVE
in the ITT population
(primary endpoint, LOCF)

-4.9% (5.0 kg)

placebo

-8.1% (8.1 kg)

CONTRAVE
(p<0.001)

41.6% of patients in the placebo

group and 42.1% of patients in the
CONTRAVE group discontinued
treatment.

BMOD: behavioural modification; ITT: intention to treat; LOCF: last observation carried forward.
Adapted from the Product Monograph.
* Intensive behavioural modification program consisting of 28 group counselling sessions over 56 weeks combined with a prescribed diet and exercise program.
† A phase 3, 56-week multicenter, double-blind, placebo-controlled study of patients with obesity (BMI ≥30 kg/m 2) or overweight (BMI ≥27 kg/m2) and at least one comorbidity (hypertension or dyslipidemia).
Patients were randomized to naltrexone (16–50 mg/day) and/or bupropion (300–400 mg/day) or placebo. Results presented are for the recommended daily dose of two 8 mg/90 mg tablets taken twice
daily for a total dose of 32 mg/360 mg. Treatment was initiated with a 3-week dose-escalation period followed by approximately 1 year of continued therapy. Treatment included an intensive behavioural
modification program consisting of 28 group counselling sessions over 56 weeks as well as a prescribed diet and exercise program. Co-primary endpoints were percent change from baseline body
weight and proportion of patients achieving ≥5% total decreased body weight. Mean baseline weight for CONTRAVE/placebo: 100.3 kg (N=565)/101.8 kg (N=196). Other mean baseline values for
CONTRAVE/placebo: waist circumference (cm) 109.3/109.0; triglycerides (mmol/L) 1.24/1.16; HDL-C (mmol/L) 1.6/1.4; LDL-C (mmol/L) 2.8/2.8; systolic blood pressure (mmHg) 116.9/116.7;
diastolic blood pressure (mmHg) 78.2/77.2; heart rate (bpm) 70.7/70.4.
In conjunction with intensive BMOD counselling*
Demonstrated effect of CONTRAVE on cardiovascular and metabolic
parameters in COR-BMOD
The effect of CONTRAVE on cardiovascular morbidity and mortality has not been established.

COR-BMOD: Change from baseline to week 56 in patients overweight or with obesity, and without diabetes 1

BMOD: behavioural modification; BP: blood pressure; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol.
* Intensive behavioural modification program consisting of 28 group counselling sessions over 56 weeks combined with a prescribed diet and exercise program.
† Least square means, from all randomized patients who had a baseline measurement and had at least one post-baseline body weight measurement while on study drug. Based on LOCF with the last on-drug
observation carried forward.
‡ Values are baseline median, median % change, and the Hodges-Lehmann estimate of the median treatment difference.
Patients with overweight or obesity and type 2 diabetes
CONTRAVE demonstrated significantly more weight loss vs. placebo
Mean change in body weight was -3.7% in the CONTRAVE 32 mg/360 mg group vs. -1.7% in the placebo group
(primary endpoint, ITT population).

COR-Diabetes: Mean change in weight over 56 weeks in the completer population 1*

2.2X more weight loss
with CONTRAVE
in the ITT population
(primary endpoint, LOCF)

-1.7% (1.8 kg)

placebo

-23.7% (3.9 kg)

CONTRAVE
(p<0.001)

41.2% of patients in the placebo

group and 47.8% of patients in the
CONTRAVE group discontinued
treatment.
ITT: intention to treat; LOCF: last observation carried forward.
Adapted from the Product Monograph.
* A phase 3, 56-week multicenter, double-blind, placebo-controlled study of patients with obesity (BMI ≥30 kg/m 2) or overweight (BMI ≥27 kg/m2) with type 2 diabetes mellitus with or without hypertension
and/or dyslipidemia and not achieving glycemic goal of a HbA1c less than 7% either with or without oral antidiabetic agents. Patients were randomized to naltrexone (16–50 mg/day) and/or bupropion
(300–400 mg/day) or placebo. Results presented are for the recommended daily dose of two 8 mg/90 mg tablets taken twice daily for a total dose of 32 mg/360 mg. Treatment was initiated with a 3-week
dose-escalation period followed by approximately 1 year of continued therapy. Treatment included a program consisting of instruction to follow a reduced-calorie diet resulting in an approximate 500 kcal/day
decrease in caloric intake, behavioural counseling, and increased physical activity. Co-primary endpoints were percent change from baseline body weight and proportion of patients achieving ≥5% total
decreased body weight. Mean baseline weight for CONTRAVE/placebo: 104.2 kg (N=321)/105.3 kg (N=166). Other mean baseline values for CONTRAVE/placebo: HbA1c (%) 8.0/8.0; fasting glucose
(mmol/L) 8.9/9.1; waist circumference (cm) 115.6/114.3; triglycerides (mmol/L) 1.7/1.9; HDL-C (mmol/L) 1.2/1.2; LDL-C (mmol/L) 2.6/2.6; systolic blood pressure (mmHg) 125.0/124.5; diastolic blood
pressure (mmHg) 77.5/77.4; heart rate (bpm) 72.9/73.1.
Demonstrated effect of CONTRAVE on cardiovascular and metabolic
parameters in COR-Diabetes
The effect of CONTRAVE on cardiovascular morbidity and mortality has not been established.

COR-Diabetes: Change from baseline to week 56 in patients overweight or with obesity, and with type 2 diabetes 1

BP: blood pressure; HbA1c: glycated hemoglobin; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol.
* Least square means, from all randomized patients who had a baseline measurement and had at least one post-baseline body weight measurement while on study drug. Based on LOCF with the last on-drug
observation carried forward.
† Values are baseline median, median % change, and the Hodges-Lehmann estimate of the median treatment difference.
Recommended daily dose: two tablets twice daily1
CONTRAVE dosing should be escalated accordingly:

In order to minimize the risk of seizures, the maximum recommended daily dose should not be exceeded.
Response to therapy should be evaluated after 12 weeks at the maintenance dosage. If a patient has not lost at least 5% of baseline body weight, discontinue CONTRAVE,
as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.
Dosage adjustments are required in patients with hepatic impairment (maximum dose 1 tablet in the morning in mild or moderate hepatic impairment) or renal
impairment (maximum dose 2 tablets, one in the morning and one in the evening in moderate or severe renal impairment), and with concomitant use of CYP2B6 inhibitors
(maximum dose 2 tablets, one in the morning and one in the evening). All patients with hepatic or renal impairment should be closely monitored for possible adverse effects
(e.g., insomnia, dry mouth, seizures) that could indicate high drug or metabolite levels.
CONTRAVE should not be taken with a high-fat meal. The tablets should not be cut, chewed, or crushed.
Blood pressure and pulse should be measured prior to starting therapy with CONTRAVE and should be monitored at regular intervals consistent with usual clinical practice.
CONTRAVE should not be given to patients with uncontrolled hypertension and should be used with caution in patients with controlled hypertension prior to treatment.
Please consult the Product Monograph for complete dosage and administration information.
Personalized support to complement your patients’ treatment journey

Financial assistance to cover up to 20%

off total prescription costs
Because each person’s weight management
experience is unique
Ongoing, one-on-one motivational coaching
from an assigned nurse counsellor • Nurse counsellors take the time to understand your
patient’s personal experience through regular phone calls
Educational and motivational content • Weekly emails with newsletters and videos provide
developed by hand-picked specialists in the ongoing education and support between check-ins
field of obesity and weight management

“It felt almost like talking to a friend. She was very personable.”
- Actual patient. May not be representative of all patient experiences.
ExperienceContrave.ca
Getting patients started on their treatment journey – adapted for virtual practice

Patients can visit the Patients use their Patients can register for
enrollment website CONTRAVE Support continued motivational
ExperienceContrave.ca Program Card to pick up and financial support
and get their CONTRAVE their first month of through the CONTRAVE
Support Program Card CONTRAVE for free at Support Program
their usual pharmacy
Clinical use: Other relevant warnings and precautions:
• The effect on cardiovascular morbidity and mortality has not been established • Interference with the action of opioid-containing drug products, vulnerability to opioid
• The safety and effectiveness in combination with other products intended for weight overdose, and precipitated opioid withdrawal
loss, including prescription drugs, over-the-counter drugs, and herbal preparations, • Increase in blood pressure and heart rate; not for use in patients with uncontrolled
have not been established. hypertension and caution in patients with controlled hypertension
• Geriatrics (≥65 years of age): Use with caution • Dependence/tolerance
• Pediatrics (<18 years of age): Not indicated • Risk of hypoglycemia in patients with type 2 diabetes on antidiabetic therapy
• Hepatotoxicity; discontinue in the event of symptoms and/or signs of acute hepatitis
Contraindications:
• Drugs metabolized by CYP2D6; do not use in combination with tamoxifen
• Uncontrolled hypertension
• Angle-closure glaucoma
• Seizure disorder or a history of seizures
• Activation of mania and hallucinations
• Use of other bupropion hydrochloride-containing products
• Allergic reactions
• Current or prior diagnosis of bulimia or anorexia nervosa
• Not recommended in nursing mothers
• Chronic opioid or opiate agonist or partial agonists use, or acute opiate withdrawal
• Closely monitor patients with hepatic and renal impairment; dose adjustments required
• Patients undergoing an abrupt discontinuation of alcohol, benzodiazepines or other
in mild to moderate hepatic impairment and moderate or severe renal impairment
sedatives and antiepileptic drugs
• Contains lactose
• Concomitant administration of monoamine oxidase inhibitors (MAOI)
• Concomitant administration of the antipsychotic thioridazine For more information:
• Pregnancy • Please consult the Product Monograph for important information relating to adverse
• Severe hepatic impairment reactions, drug interactions, and dosing information which have not been discussed in
• End-stage renal failure this piece. The Product Monograph is also available by calling 1-800-361-4261.
References:
Most serious warnings and precautions: 1. CONTRAVE Product Monograph. Bausch Health, Canada Inc.
• Potential association with behavioural and emotional changes, including self-harm: 2. Wharton S, Lau DCW, Vallis M et al. Obesity in adults: a clinical practice guidelines. CMAJ 2020;192:E875-91.
monitor for suicidal ideation and for agitation-type emotional and behavioural changes 3. Kirk S, Ramos Salas X, Alberga AS, Russl-Mayhew S. Reducing Weight Bias, Stigma and Discrimination in
• Seizures: to minimize the risk of seizures, the maximum recommended daily dose Obesity Management, Practice Policy. Available from: https://obesitycanada.ca/guidelines/weightbias. Accessed
December 8, 2020.
should not be exceeded 4. Pedersen SD, Manjoo P, Wharton S. Canadian Adult Obesity Clinical Practice Guidelines: Pharmacotherapy in
Obesity Management. Available from: https://obesitycanada.ca/guidelines/pharmacotherapy. Accessed October
26, 2020.
CONTRAVE and the CONTRAVE logo are registered trademarks of Nalpropion Pharmaceuticals, Inc., used under license.
© 2021 Bausch Health, Canada Inc. Laval, Québec H7L 4A8. All rights reserved.
The information is intended only for residents of Canada.