What is bupropion-naltrexone and how does it work?

Peanut butter and jelly are two completely different ingredients that come together to form something new: the world’s greatest sandwich. That’s what happens with bupropion-naltrexone. Individually, bupropion and naltrexone have completely different uses: bupropion is an antidepressant and naltrexone is an opioid antagonist. But when they join forces, they form an effective oral medication for weight loss. Keep reading to learn more about how bupropion-naltrexone works, who might be a good candidate for it, and what kind of side effects you might experience.

What is bupropion-naltrexone?

Bupropion-naltrexone is a combination of two medications used for weight loss in adults over the age of 18. Prescribed as either a generic or under the brand name Contrave, which is a single pill FDA approved in 2014, it’s a combination of two medications: bupropion and naltrexone.

What is bupropion?

Bupropion is an FDA-approved antidepressant. It’s the active ingredient in the antidepressants Wellbutrin and Aplenzin, and in the smoking-cessation aid Zyban. “Bupropion works by inhibiting the reuptake of two neurotransmitters in the brain: dopamine and norepinephrine,” says Dr. Matthew Poplin, M.D., diplomate of the American Board of Obesity Medicine. “By reducing the removal of these molecules, the amount of active dopamine and norepinephrine is increased, helping people feel their positive effects longer.” The same properties that can improve depression symptoms may also help with weight loss, since dopamine and norepinephrine stimulate certain neurons in the brain that suppress your appetite and improve satiety, Poplin says. “Bupropion also may reduce large fluctuations in dopamine, especially when associated with food or eating,” he says. “This likely helps you feel more in control over cravings.”

What is naltrexone?

Naltrexone is a medication that’s FDA-approved to treat alcohol use disorder and opioid dependence. “It binds to opioid receptors in the body, but instead of activating them, it blocks them from being activated by opioids,” says Poplin. By removing the euphoric effects of alcohol and opioids, including prescription opioid pain medication and heroin, naltrexone decreases someone’s dependence on them. Something similar happens with eating. Naltrexone helps bupropion suppress appetite and also blocks the opioids associated with food pleasure, says Poplin. The result: You don’t get the same feel-good “hit” when you eat foods like chips, pizza, and sweets.

Bupropion-naltrexone brand name

Bupropion-naltrexone can be prescribed as two separate generic pills. It’s also available as a single pre-combined pill under the brand name Contrave. Like all weight-loss medications, Contrave should be used in tandem with a reduced-calorie diet and increased physical activity.

Bupropion-naltrexone uses

Together, bupropion and naltrexone can be prescribed for weight loss in adults over 18. You shouldn’t take the combination of bupropion and naltrexone if you’re trying to treat depression or substance use disorders — the medications should be used separately for those purposes.

What is bupropion-naltrexone used for?

It’s used for weight loss in adults who have obesity or overweight, and should be paired with healthy lifestyle changes. When used in conjunction with a reduced-caloried diet and increased physical activity, clinical trials found that people lost an average of 6% of their initial body weight after 56 weeks.

How does bupropion-naltrexone work?

In combination, the two drugs work in the brain to reduce appetite and food cravings, which can help people lose weight. “Bupropion acts on neurotransmitters in the hypothalamus to regulate appetite, while naltrexone blocks ‘pleasure’ receptors in the brain,” says Dr. Jennifer Brown, M.D., a board-certified obesity medicine and family medicine physician at Maxwelton Health Center in West Virginia.

Bupropion-naltrexone dosage

Bupropion-naltrexone is a dual-action oral medication for weight loss. In generic form, people take one tablet of bupropion and one tablet of naltrexone together. (Contrave is just one tablet with both active ingredients in it.)

Your provider will likely start you with one tablet a day of bupropion XL (extended release) and half of a tablet of naltrexone Hcl, and then gradually increase your dosage as needed.

It’s recommended to take both tablets in the morning. (Contrave, however, is taken twice a day.) If you miss a dose, wait until your next regular time to take it. Do not take more than one dose at a time or double up if you’ve missed a dose. And do not chew or crush the tablets.

Forms and strengths

Bupropion-naltrexone comes as tablets, with each drug available in two strengths. Bupropion XL comes in 150 mg and 300 mg tablets. Naltrexone Hcl is available in 25 mg or 50 mg tablets.

Bupropion-naltrexone side effects

Everyone can react differently to bupropion-naltrexone, but here are some of the side effects you might experience.

Common side effects

The most common bupropion-naltrexone side effects are:

• Nausea: 32.5% compared to 6.7% taking placebo
• Constipation: 19.2% compared to 7.2% taking placebo
• Headache: 17.6% compared to 10.4% taking placebo
• Dizziness: 9.9% compared to 3.4% taking placebo
• Insomnia: 9.2% compared to 5.9% taking placebo
• Vomiting: 8.1% compared to 2.3% taking placebo

These are likeliest to happen when you start taking the medication and typically fade as your body adjusts to it. To minimize side effects, your provider will typically start you with a small dose and slowly increase it over the following weeks.

Serious side effects

Although rare, the most serious side effects of bupropion-naltrexone are increased risk of seizure, risk of overdose if you’re also using opioids, or risk of opioid withdrawal symptoms. All opioid usage should be stopped at least seven to 10 days before starting bupropion-naltrexone.

Other serious side effects include increased blood pressure and heart rate and, less commonly, liver damage or hepatitis, vision problems, increased risk of low blood sugar in people with type 2 diabetes, or manic episodes.

In rare cases, some people have experienced severe allergic reactions to bupropion, including rash, hives, swelling of the mouth and tongue, itching, and trouble breathing. Seek medical attention right away if you have any of these symptoms.

You should also seek medical care if you or someone taking the medication has the following:

• Trouble breathing
• Very drowsy with slowed breathing
• Slow, shallow breathing (little chest movement with breathing)
• Feeling faint, very dizzy, confused, or has unusual symptoms

Alternatives to bupropion-naltrexone

Bupropion-naltrexone is one of several prescription medications approved for weight loss. Here are the others:

• GLP-1s: Wegovy (semaglutide), Zepbound (tirzepatide), and Saxenda (liraglutide) are injectable GLP-1 medications approved for weight loss. They work by mimicking the action of a naturally occurring hormone, GLP-1, to reduce appetite and slow gastric emptying so you feel full longer.
  
  
• Xenical, Alli (orlistat): Orlistat is an oral weight loss medication that prevents excess fat in food from being absorbed in the intestines. Xenical is the prescription version and Alli is sold over the counter.
  
  
• Qsymia (phentermine-topiramate): Another combination medication, phentermine-topiramine are oral capsules that work together to reduce appetite and make you feel full longer after you eat.
  
  
• Metformin: Metformin is an oral medication approved to treat type 2 diabetes, but can be prescribed off-label for weight loss. It works by lowering blood glucose levels, which can decrease appetite.

Bupropion-naltrexone warnings and precautions

While there is no black box warning — the FDA’s most serious designation — for naltrexone, there is one for bupropion. The medication has the potential to increase suicidal thoughts or behavior. Let your healthcare provider know right away if you experience suicidal thoughts or ideation while taking bupropion.

This side effect is extremely rare. In a 56-week clinical trial of Contrave (equivalent to bupropion doses of 360 mg/day), no suicides or suicide attempts were reported. Of 3,239 patients taking Contrave during these trials, suicidal ideation was reported by 1 (0.03%) compared to 3 reports among the 1,515 patients taking a placebo.

Beyond that, you should tell your provider if you have any of the following conditions, as bupropion-naltrexone can make them worse:

• Uncontrolled high blood pressure
• Seizures
• Anorexia or bulimia nervosa

Bupropion-naltrexone interactions

According to the manufacturer, you should not drink a lot of alcohol while taking this medication. You should also not take it if you:

• Have taken MAOI antidepressants in the past 14 days
• Take other medications containing bupropion, such as Wellbutrin or Zyban
• Have used opioids or any medications containing opioids, such as cold or cough medicine, within the past seven to 10 days
• Have recently or abruptly stopped drinking alcohol or taking certain drugs, including benzodiazepines, barbiturates, or anti-epileptics

Bupropion-naltrexone cost

Weight-loss medications aren’t always covered by health insurance, so you’ll need to check your individual plan to see if bupropion-naltrexone is covered or not, as well as if your doctor needs to request prior authorization for you.

Bupropion and naltrexone are both generic medications. Costs vary at different pharmacies, but what you pay out-of-pocket should be low. For instance, qualified members of WW Clinic can get it for free with membership. That said, if you go with the brand-name Contrave, it can cost several hundred dollars a month without insurance (the current coupon card has it priced at $199 per month).

In comparison, injectable GLP-1 medications for weight loss — like Wegovy and Zepbound — cost far more. Wegovy’s list price is $1,349.02 per package, and Zepbound costs $1,086.37 per package, though each of their manufacturers also offer savings programs to reduce cost.

The bottom line

Bupropion-naltrexone is an oral weight loss medication. When used in conjunction with a reduced-caloried diet and increased physical activity, people typically lose an average of 6% of their body weight. Taken orally, it’s a combination of two medications — bupropion and naltrexone — which work together to curb cravings and reduce appetite, especially when emotional eating or overeating is present. Because it’s an oral medication and available in generic form, it costs far less than injectable brand name GLP-1 medications for weight loss.