Naltrexone and Bupropion

Naltrexone and bupropion, sold as Contrave, has one supported use:

• Contrave is used with a reduced-calorie diet and more physical activity to reduce excess body weight and maintain weight loss long term in adults with obesity, or overweight with at least one weight-related condition.
• Its effect on heart disease and death from heart problems has not been established.

Contrave has two parts. Naltrexone blocks opioid receptors. Bupropion weakly blocks the reuptake of dopamine and norepinephrine, two brain chemicals.

Lab studies suggest the combination acts on the hypothalamus (the brain’s appetite control center) and the reward system involved in eating. The exact way it leads to weight loss is not fully understood.

Contrave is taken by mouth, morning and evening. The dose is increased step by step over the first weeks, so you start low and build up.

• Swallow tablets whole. Do not cut, chew, or crush them.
• Do not take it with a high-fat meal.
• Your prescriber should check your progress after 12 weeks at the full dose and may stop it if weight loss is too small.
• Some people with kidney or liver problems, or who take certain other drugs, need a lower maximum dose.

Follow your prescriber’s directions and the label.

The most common side effects are mostly stomach and nervous system related:

• Nausea (the most common)
• Constipation
• Headache
• Vomiting
• Dizziness
• Trouble sleeping
• Dry mouth
• Diarrhea

Nausea was the most common reason people stopped taking it. Call your doctor about mood changes, suicidal thoughts, seizures, allergic reactions, or a racing heartbeat.

• Suicidal thoughts and behavior: This is a boxed warning. Watch for new or worsening depression or mood changes, especially early on and in younger people.
• Seizures: Risk is lowered by following the dosing schedule and avoiding high-fat meals.
• Blood pressure and heart rate: These can rise, especially in the first three months, and should be monitored.
• Liver problems: Hepatitis and liver dysfunction have been seen with naltrexone.
• Angle-closure glaucoma: A sudden rise in eye pressure can occur in people with narrow angles in the eye.
• Low blood sugar: Weight loss can cause this in people taking diabetes medicines.
• Smoking cessation: Serious mood and behavior changes have been reported in people trying to quit smoking.

Contrave can clash with several kinds of medicines:

• MAOI antidepressants, linezolid, and intravenous methylene blue: risk of dangerous blood pressure reactions.
• Other bupropion products: not allowed together with Contrave.
• Opioid medicines: Contrave can block their effects.
• Drugs cleared by CYP2D6 (certain antidepressants, antipsychotics, metoprolol, flecainide, propafenone): bupropion can raise their levels.
• Clopidogrel and ticlopidine: raise bupropion levels, so the dose is limited.
• Ritonavir, lopinavir, efavirenz: lower bupropion levels and may make it less effective.
• Drugs that lower the seizure threshold: higher seizure risk.
• Levodopa and amantadine: possible nervous system toxicity.
• Digoxin: levels may drop.
• Alcohol: can cause neuropsychiatric effects and lower alcohol tolerance, so minimize or avoid it.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not use it with uncontrolled high blood pressure or a seizure disorder.
• Do not use it with bulimia or anorexia nervosa.
• Do not use it with chronic opioid use or acute opioid withdrawal.
• Do not use it when suddenly stopping alcohol, benzodiazepines, barbiturates, or seizure medicines.
• Do not use it with an allergy to bupropion, naltrexone, or its ingredients.
• Pregnancy: stop it if you become pregnant, since weight loss may harm the baby.
• Breastfeeding: both medicines pass into breast milk, so discuss with your doctor.
• Children under 18: not recommended.
• Adults over 65: use with caution.
• Kidney or liver disease: lower maximum dose may be needed, and it is not recommended for end-stage kidney disease or severe liver impairment.

Overdoses of the bupropion part have caused seizures, hallucinations, loss of consciousness, fast heartbeat, and heart rhythm changes. Deaths have been reported with large doses. If you take too much, call poison control at 1-800-222-1222. There is no known antidote, so care focuses on supportive treatment and monitoring.

In lab studies, the combination increased the firing of appetite-regulating neurons in the hypothalamus. It also reduced food intake in mice when given directly into a brain reward area. At the recommended dose, it does not meaningfully prolong the QTc interval (a heart rhythm measure).

Naltrexone peaks in the blood at about 2 hours and bupropion at about 3 hours. A high-fat meal substantially raises levels of both, which is why it should not be taken with one. Both are broken down into active metabolites and cleared mostly through the kidneys. The half-life is about 5 hours for naltrexone and about 21 hours for bupropion, and bupropion metabolites reach steady levels in about a week.

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) .