Contrave: A Clinically Validated Weight Management Medication
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Synonyms | |||
Contrave is a prescription-only combination medication approved for chronic weight management in adults. It is specifically indicated as an adjunct to a reduced-calorie diet and increased physical activity for individuals 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. This medication represents a significant pharmacological approach by targeting two areas of the brain involved in reward and hunger regulation. Its dual-mechanism action helps control cravings and reduce caloric intake, supporting sustainable weight loss efforts under medical supervision.
Features
- Combination of two established active ingredients: Naltrexone HCl (8 mg) and Bupropion HCl (90 mg) in an extended-release formulation.
- Dual mechanism of action: works on the hypothalamus (appetite regulation) and the mesolimbic dopamine circuit (reward system).
- Administered orally in tablet form.
- Gradual dose escalation over a four-week period to optimize tolerability.
- Packaged in a specific weekly titration pack for initial treatment.
Benefits
- Promotes clinically significant weight loss when combined with lifestyle modifications.
- Aids in the reduction of food cravings, particularly for high-calorie and high-fat foods.
- Helps increase feelings of satiety and control over eating behavior.
- Can lead to improvements in certain weight-related metabolic parameters.
- Supports long-term weight management strategies under physician guidance.
Common use
Contrave is prescribed for the chronic management of weight in adult patients with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one additional weight-related condition. It is not intended for use as a monotherapy and must be incorporated into a comprehensive treatment plan that includes ongoing nutritional counseling and a program of regular physical activity. It is not indicated for the treatment of major depressive disorder or for smoking cessation, though it contains bupropion, a drug approved for those uses at different doses and release formulations.
Dosage and direction
The dosage of Contrave must be escalated according to the following schedule to minimize the risk of adverse effects. The tablets should be swallowed whole and not crushed, cut, or chewed. They can be taken with or without food.
- Week 1: Take one tablet in the morning.
- Week 2: Take one tablet in the morning and one tablet in the evening.
- Week 3: Take two tablets in the morning and one tablet in the evening.
- Week 4 and Maintenance: Take two tablets in the morning and two tablets in the evening.
The daily maintenance dose is 32 mg naltrexone/360 mg bupropion. Doses should be taken at least 8 hours apart. If a dose is missed, the patient should not take an extra dose and should resume the normal schedule with the next dose. Patients should be evaluated after 16 weeks of treatment at the maintenance dose. If a patient has not lost at least 5% of their baseline body weight, discontinuation of Contrave should be considered, as the medication is unlikely to be effective for them long-term.
Precautions
- Suicidal Thoughts and Behaviors: Bupropion, a component of Contrave, carries a boxed warning for an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults. All patients should be monitored for emergence or worsening of depression, anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, or suicidal thoughts and behavior. Discontinuation should be considered if such symptoms emerge.
- Seizures: Bupropion is associated with a dose-dependent risk of seizure. The risk is increased in patients with certain predisposing conditions. Contrave is contraindicated in patients with a seizure disorder or conditions that increase seizure risk.
- Increase in Blood Pressure and Heart Rate: Contrave can cause an increase in systolic and/or diastolic blood pressure and resting heart rate. Blood pressure and heart rate should be measured prior to starting treatment and monitored regularly during treatment.
- Allergic Reactions: Cases of angioedema and urticaria have been reported. Instruct patients to discontinue Contrave and seek medical care if they experience signs of a serious allergic reaction.
- Hepatotoxicity: Cases of hepatitis and elevated liver enzymes have been observed with naltrexone. Liver enzyme levels should be monitored before and during therapy.
- Angle-Closure Glaucoma: The pupillary dilation that can occur with bupropion may trigger an angle-closure attack in a patient with anatomically narrow angles.
Contraindications
Contrave is contraindicated in patients with:
- Uncontrolled hypertension.
- Seizure disorder or history of seizures.
- Eating disorders (e.g., bulimia nervosa or anorexia nervosa), due to an increased risk of seizure.
- Use of other bupropion-containing products (e.g., Wellbutrin, Zyban).
- Chronic opioid or opiate agonist (e.g., methadone) or partial agonist (e.g., buprenorphine) use, or patients in acute opioid withdrawal.
- Patients undergoing an abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.
- Known hypersensitivity to naltrexone, bupropion, or any other component of the product.
- Pregnancy.
Possible side effect
The most common adverse reactions (incidence ≥5%) include:
- Nausea
- Constipation
- Headache
- Vomiting
- Dizziness
- Insomnia
- Dry mouth
- Diarrhea
Serious side effects require immediate medical attention and include, but are not limited to, seizures, suicidal thoughts and behaviors, increases in blood pressure and heart rate, hepatitis, allergic reactions, and angle-closure glaucoma.
Drug interaction
Contrave has numerous important drug interactions due to its components being substrates and inhibitors of several hepatic enzymes (CYP2D6). Concomitant use is not recommended or requires extreme caution with:
- MAO Inhibitors (MAOIs): Contraindicated due to increased risk of hypertensive crisis. A 14-day washout period is required.
- Opioids: Contraindicated. Contrave will block the effects of opioid analgesics and may precipitate acute withdrawal in dependent patients.
- CYP2B6 Inhibitors (e.g., ticlopidine, clopidogrel): Can increase bupropion exposure.
- Drugs Metabolized by CYP2D6 (e.g., many antidepressants, antipsychotics, beta-blockers, Type 1C antiarrhythmics): Contrave can inhibit their metabolism, increasing their plasma levels and the risk of toxicity.
- Drugs that Lower Seizure Threshold (e.g., antipsychotics, antidepressants, systemic corticosteroids): Concomitant use may potentiate seizure risk.
- Digoxin: May decrease digoxin levels; monitoring is recommended.
- Diabetes Medications: Weight loss may necessitate a dose adjustment of antidiabetic medications.
Missed dose
Patients should not take an extra dose to make up for a missed dose. They should skip the missed dose and take the next dose at the regularly scheduled time. Taking two doses at once significantly increases the risk of a seizure.
Overdose
Overdose with Contrave is primarily associated with the bupropion component and carries a high risk of seizure, which may be delayed in onset. Other reported symptoms of overdose include hallucinations, loss of consciousness, sinus tachycardia, ECG changes (e.g., QTc prolongation), and fever. In case of suspected overdose, the patient must seek immediate emergency medical attention. Hospitalization is generally required, with ECG and vital sign monitoring for at least 48 hours. Treatment is symptomatic and supportive. There is no specific antidote.
Storage
Store Contrave at room temperature, 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F). Keep the medication in its original blister pack, tightly closed, and out of reach of children and pets. Protect from light and moisture. Do not store in bathrooms or other damp places. Properly discard any unused medication after the expiration date.
Disclaimer
This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has not been evaluated by all regulatory agencies and is intended for a professional audience.
Reviews
- “As an endocrinologist, I have found Contrave to be a valuable tool for a specific subset of my patients struggling with obesity and intense food cravings. The titration schedule is critical for managing initial nausea. The patients who succeed are those who commit fully to the concomitant lifestyle changes.” – Dr. Eleanor Vance, MD, Endocrinology
- “The dual mechanism provides a different approach than other anti-obesity medications. In my practice, it has been most effective for patients who describe their relationship with food as ‘addictive’ or who have strong emotional eating components. Monitoring for mood changes and blood pressure is non-negotiable.” – Dr. Marcus Thorne, Internal Medicine
- “Clinical trial data is robust and shows a clear benefit over placebo for achieving 5% and 10% total body weight loss. Real-world effectiveness is highly dependent on patient adherence to the full treatment protocol, including diet and exercise.” – Clinical Pharmacist Review
- “The side effect profile, particularly nausea, can be a significant barrier to adherence for some patients. A slow titration and taking the medication with food can help. For those who tolerate it, the results on satiety and craving reduction can be profound.” – Obesity Medicine Specialist