Contrave is a prescription-only weight management medication approved for use in adults with obesity or overweight with at least one weight-related comorbidity. It combines two established active ingredients—naltrexone HCl and bupropion HCl—in an extended-release formulation, working on specific areas of the brain involved in hunger control, cravings, and reward-based eating behaviors. This medication is intended as an adjunct to a reduced-calorie diet and increased physical activity, offering a pharmacologically supported approach to long-term weight loss when lifestyle modifications alone prove insufficient. Clinical trials have demonstrated its efficacy in promoting significant and sustained weight reduction over 56 weeks, alongside improvements in cardiometabolic parameters.

Features

• Contains naltrexone hydrochloride (8 mg) and bupropion hydrochloride (90 mg) in an extended-release tablet
• Dual mechanism targets the hypothalamus (appetite regulation) and mesolimbic dopamine pathway (reward system)
• Gradual dose escalation over four weeks to minimize initial side effects
• Recommended as part of a comprehensive weight management program including diet and exercise
• Available only by prescription following medical evaluation

Benefits

• Supports clinically meaningful weight loss—an average of 5–10% of total body weight in studies
• Helps reduce food cravings, particularly for high-calorie and sweet foods
• May improve glycemic parameters in patients with type 2 diabetes
• Can contribute to improved cardiovascular risk factors, such as waist circumference and triglyceride levels
• Aids in long-term weight maintenance when combined with behavioral support
• Non-stimulant mechanism avoids amphetamine-like side effects

Common use

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 (obesity), or
• 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes, or dyslipidemia.

Treatment should be initiated only after thorough medical assessment and exclusion of contraindications. It is not recommended for use in patients with a history of seizures, eating disorders, or opioid dependence.

Dosage and direction

The recommended dosage involves a 4-week titration schedule to reach the maintenance dose:

• Week 1: One tablet (8 mg naltrexone/90 mg bupropion) in the morning
• Week 2: One tablet in the morning and one tablet in the evening
• Week 3: Two tablets in the morning and one tablet in the evening
• Week 4 and maintenance: Two tablets in the morning and two tablets in the evening

Tablets should be swallowed whole and not crushed, divided, or chewed. Doses should be taken with food to reduce the incidence of nausea. Maximum daily dose should not exceed 32 mg naltrexone/360 mg bupropion.

Precautions

• Monitor blood pressure and heart rate regularly, especially during initial titration
• Evaluate patients for history of bipolar disorder, depression, or suicidal ideation
• Use with caution in patients with hepatic or renal impairment
• Not recommended in elderly patients with age-related renal decline
• May lower seizure threshold; avoid in patients with predisposing conditions
• Discontinue if clinically significant or persistent hypertension develops

Contraindications

• Uncontrolled hypertension
• Seizure disorder or history of seizures
• Concomitant use of monoamine oxidase inhibitors (MAOIs)
• Current or prior diagnosis of bulimia or anorexia nervosa
• Chronic opioid use, opioid dependence, or acute opioid withdrawal
• Pregnancy or breastfeeding
• Known hypersensitivity to naltrexone, bupropion, or any component of the formulation

Possible side effects

Common adverse reactions (≥5%) include:

• Nausea (32.5%)
• Constipation (19.2%)
• Headache (17.6%)
• Vomiting (10.7%)
• Dizziness (9.9%)
• Insomnia (9.2%)
• Dry mouth (8.1%)
• Diarrhea (7.3%)

Serious but less frequent side effects may include:

• Increased blood pressure or heart rate
• Seizures
• Angle-closure glaucoma
• Liver toxicity
• Suicidal thoughts or behaviors
• Hypersensitivity reactions

Drug interaction

Contrave has significant interaction potential due to its bupropion component (CYP2D6 inhibitor) and naltrexone metabolism:

• MAOIs: Contraindicated within 14 days of each other
• Opioids: Reduced efficacy and potential precipitation of withdrawal
• Antidepressants (SSRIs, TCAs, antipsychotics): Increased levels of co-administered drugs
• Drugs metabolized by CYP2D6 (e.g., beta-blockers, antipsychotics): May require dose adjustment
• Alcohol: Avoid excessive consumption due to seizure risk
• Diabetes medications: May require adjustment due to weight loss effects

Missed dose

If a dose is missed, patients should take the next dose at the regular time. Do not double the dose to make up for a missed one. If multiple doses are missed, re-initiate therapy according to the titration schedule under medical supervision.

Overdose

Overdose may manifest as:

• Seizures
• Hallucinations
• Sinus tachycardia
• ECG changes (QRS widening, QT prolongation)
• Altered consciousness
• Nausea/vomiting

In case of suspected overdose, seek immediate medical attention. Provide supportive care with ECG and vital sign monitoring. There is no specific antidote; benzodiazepines may be used for seizure control.

Storage

Store at room temperature (20–25°C/68–77°F) in the original container. Keep tightly closed and protect from moisture and light. Keep out of reach of children and pets. Do not use if tablets are crushed, broken, or discolored.

Disclaimer

This information is for educational purposes only and does not replace professional medical advice. Contrave is available by prescription only after thorough evaluation by a qualified healthcare provider. Individual results may vary. Patients should discuss all medical conditions and medications with their physician before starting treatment. Not all side effects or interactions are listed here.

Reviews

Clinical trial data (COR-I, COR-II, COR-BMOD, COR-Diabetes) demonstrated:

• 42–48% of patients achieved ≥5% weight loss vs. 16–17% with placebo
• 21–25% achieved ≥10% weight loss vs. 7–10% with placebo
• Improvements in waist circumference, HDL cholesterol, triglycerides, and glycemic control in diabetic patients

Real-world evidence suggests similar efficacy with appropriate patient selection and adherence to lifestyle modifications. Most common reasons for discontinuation include gastrointestinal side effects during titration and inadequate insurance coverage.