Naltrexone-bupropion (Contrave) is a prescription pill for long-term weight management in adults. One extended-release tablet holds two older medicines: naltrexone, which blocks opioid receptors, and bupropion, an antidepressant. US labeling clears it for use alongside a reduced-calorie diet and more physical activity, not as a stand-alone fix.
That last part is not filler. The approved product is Contrave Extended-Release, made by Nalpropion Pharmaceuticals, and it is a human prescription drug taken by mouth. It is not a GLP-1 injection, it is not a stimulant, and it is not approved to treat depression or to help people quit smoking, even though bupropion on its own is approved for both under different brand names.
This page walks through what is inside the tablet, how it is thought to work, the side effects and warnings that matter most, how it stacks up against injectable options, and what actually moves the monthly price when you pay yourself.
What is in the tablet and what it is approved to do
Each tablet is a fixed-dose combination: 8 mg of naltrexone hydrochloride and 90 mg of bupropion hydrochloride in an extended-release form. Extended-release means the tablet releases the drug slowly, so it has to be swallowed whole rather than split, crushed or chewed.
US labeling covers one job: reducing excess body weight and helping keep that weight off long term in adults who have obesity, or who are overweight and also have at least one weight-related health problem. Common examples of those problems include high blood pressure, type 2 diabetes and high cholesterol.
Both ingredients have long histories on their own. Naltrexone is used in addiction medicine, for alcohol and opioid dependence. Bupropion is used for depression and, in a different formulation, for smoking cessation. The combination product is approved only for weight management, and only in adults. A detailed clinical summary of how the two were paired is available in a peer-reviewed pharmacy review of the combination.
How the naltrexone and bupropion pairing is thought to work
Neither ingredient was designed as a weight-loss drug. The theory behind putting them together involves two parts of the brain.
The first is the hypothalamus, which helps set hunger levels. Bupropion stimulates a group of nerve cells there that release chemicals linked to reduced appetite. Those same cells release beta-endorphin, which then feeds back and switches the cells off again. Naltrexone blocks that feedback loop, so the appetite-related signal keeps running longer.
The second is the brain’s reward system, which drives the pull toward specific foods rather than plain hunger. Both ingredients act on that circuit, which is why some people describe fewer food cravings rather than a smaller stomach.
Honest caveat: labeling states the exact way this combination produces weight loss is not fully understood. Clinical trials over about a year showed greater average weight loss than placebo, though average results in trials are not a prediction for any one person, and results were reported alongside diet and activity changes. Patient-facing summaries from a major US hospital system describe the same appetite and craving effects in plain terms.
Who the label says this pill is for
Eligibility is written around body mass index, or BMI, a height-and-weight ratio used as a rough screen. Labeling points to adults with a BMI of 30 or higher, or a BMI of 27 or higher plus at least one weight-related condition. It is not approved for anyone under 18.
If you want to see roughly where you sit before a consultation, this runs the same arithmetic a clinician does:
BMI calculator
Most weight-loss programmes screen on BMI before they will prescribe. This is the number they will use.
A screening number, not a diagnosis. It does not distinguish muscle from fat, and it reads high for muscular builds.
BMI is a screen, not a diagnosis. It does not account for muscle mass, body shape or ethnicity, so clinicians look at waist size, blood pressure, blood sugar and cholesterol too. Federal patient education on prescription medicines for overweight and obesity explains how those factors fit together.
Labeling also builds in a stopping rule. If you have not lost at least 5 percent of your starting weight after 12 weeks on the full maintenance dose, continuing is not expected to help, and the medicine is meant to be stopped. That single rule is worth knowing before you sign up for anything, because it sets a realistic checkpoint rather than an open-ended commitment.
In practice, people ask about this option for a few reasons: they prefer a pill to a weekly injection, they describe cravings or evening eating as their main obstacle, or injectable options are out of reach on cost. None of those preferences override the safety screening below.
Dosing pattern, forms and the four-week ramp
The product comes as one tablet strength. Labeling describes a gradual increase over four weeks, starting with a single tablet in the morning and building to two tablets twice a day, which is the maintenance amount of 32 mg naltrexone and 360 mg bupropion per day. Nobody should exceed two tablets in one dose or four in a day, and the ramp exists mainly to blunt nausea.
A few practical points from labeling rather than from advice:
- Tablets are swallowed whole. Breaking the extended-release coating changes how fast the drug is absorbed.
- Taking a dose with a high-fat meal raises blood levels of both ingredients, so that combination is avoided.
- People with reduced kidney or liver function may be capped at a lower daily amount, and some are advised against it entirely.
- Missed doses are not doubled up.
Your prescriber and the official prescribing information are the authority on your specific schedule. Do not adjust a dose based on a web page, including this one.
Side effects reported most often
Most side effects show up in the first weeks, while the dose is climbing, and many ease afterward. In clinical trials the most common by far was nausea, reported by roughly one in three participants. Constipation and headache were next, each in the range of one in five or fewer.
Other frequently reported effects included vomiting, dizziness, trouble sleeping, dry mouth and diarrhea. Some people report jitteriness, sweating, ringing in the ears or a change in taste. Nausea was also the leading reason people stopped the medicine during studies, which is a useful signal: this is a tolerability question as much as an effectiveness one. The Mayo Clinic side effect listing for this combination groups them by how often they occur.
Two effects deserve separate mention because they are easy to miss. Blood pressure and heart rate can rise, on average modestly, and that rise can matter for anyone whose blood pressure is already borderline, so monitoring is part of the deal. And because bupropion is stimulating for some people, insomnia is common enough that dose timing gets discussed.
Boxed warning, serious risks and who should not take it
US labeling carries a boxed warning, the strongest warning the FDA applies, about suicidal thoughts and behavior. Antidepressants, including bupropion, are linked to increased risk of suicidal thinking and behavior in children, adolescents and young adults. Anyone taking this combination should be watched for new or worsening depression, mood changes, agitation or thoughts of self-harm, especially early on and after any dose change. If those symptoms appear, labeling directs that the medicine be stopped. It is not approved for anyone under 18, and it is not approved to treat depression.
Postmarketing reports tied to bupropion used for smoking cessation include serious neuropsychiatric events: mood swings, mania, psychosis, hallucinations, paranoia, hostility, agitation, anxiety and panic, as well as suicidal ideation and suicide. Those reports are part of why this medicine gets close follow-up rather than a one-and-done prescription.
Other labeled risks include:
- Seizures. Bupropion lowers the seizure threshold. Seizures occurred in about 0.1 percent of participants in the combination trials, and the medicine is stopped permanently if one occurs.
- Opioid problems. Naltrexone can trigger sudden opioid withdrawal in someone using opioids, and it blocks the effect of opioid pain relief. After stopping, opioid tolerance may be lower, which raises overdose risk if someone returns to a previous dose.
- Liver injury. Naltrexone has been linked to hepatotoxicity, so symptoms such as yellowing eyes, dark urine or right-sided belly pain are taken seriously.
- Blood pressure and heart rate increases, including in people with controlled hypertension.
- Angle-closure glaucoma, an eye pressure emergency, in people with narrow drainage angles.
- Low blood sugar in people taking insulin or certain diabetes pills, since weight loss changes their needs.
- Manic episodes in people with bipolar disorder or a family history of it.
- Serious allergic reactions, including rash with swelling, and rare severe skin reactions.
Labeling lists absolute contraindications, meaning situations where the medicine is not used at all: uncontrolled high blood pressure; a seizure disorder or history of seizures; use of any other bupropion-containing product; current or past bulimia or anorexia nervosa; chronic opioid use or acute opioid withdrawal; abrupt stopping of alcohol, benzodiazepines, barbiturates or antiseizure medicines; use of a monoamine oxidase inhibitor within the past 14 days; and known allergy to any ingredient. Weight loss is also not recommended during pregnancy, so the medicine is stopped if pregnancy occurs.
Drug interactions and what to avoid while taking it
This combination has a long interaction list, mostly driven by the bupropion half. Bring a full medicine list, including supplements, to any consultation.
- MAO inhibitors such as phenelzine, tranylcypromine and linezolid. A 14-day gap is required in both directions.
- Any opioid, including prescription pain medicines, cough syrups containing codeine, methadone and buprenorphine.
- Other bupropion products, including those sold for smoking cessation. Doubling up raises seizure risk.
- Medicines processed by the CYP2D6 enzyme. Bupropion slows that enzyme, which can raise levels of some antidepressants, tricyclics, beta blockers such as metoprolol, certain heart rhythm drugs, and can reduce the activation of tamoxifen.
- Drugs that affect bupropion levels, including ritonavir, efavirenz, carbamazepine, ticlopidine and clopidogrel.
- Anything that lowers the seizure threshold, such as some antipsychotics, theophylline and systemic steroids.
- Dopamine-related medicines such as levodopa and amantadine, which can add to side effects.
- Digoxin and warfarin, where blood levels or clotting tests may shift.
On the everyday side: alcohol is limited or avoided, because heavy drinking plus bupropion raises the risk of neuropsychiatric effects and seizures, and abruptly quitting heavy drinking is itself a contraindication. High-fat meals are avoided at dose time. And this combination can cause a false positive for amphetamines on a urine drug screen, which is worth flagging before employment or clinical testing.
How it compares with GLP-1 medicines, phentermine and bupropion alone
Two of the most common questions are whether an injectable is better and whether this is just a repackaged antidepressant. Short answers: the injectables have produced larger average weight loss in their own trials, and no, the combination is not approved or dosed like an antidepressant.
| Option | Form | What US labeling covers | What people weigh up |
|---|---|---|---|
| Naltrexone-bupropion ER | Oral tablet, taken daily | Long-term weight management in adults with obesity, or overweight plus a related condition | Pill instead of injection; boxed warning; nausea and blood pressure monitoring |
| Semaglutide | Weekly injection | Weight management under one brand; type 2 diabetes under another | Larger average loss in trials; GI side effects; supply and cost swings |
| Tirzepatide | Weekly injection | Weight management under one brand; type 2 diabetes under another | Largest average loss reported in its trials; injection; cost |
| Phentermine | Oral, stimulant-type appetite suppressant | Short-term use as an addition to weight reduction | Inexpensive and familiar; short-term framing; not for uncontrolled hypertension |
| Bupropion alone | Oral tablet | Depression and, separately, smoking cessation | Not approved for weight loss on its own; cannot be combined with the ER pairing |
Ozempic is the semaglutide brand approved for type 2 diabetes, and Wegovy is the semaglutide brand approved for weight management, so asking whether Ozempic beats this pill compares two products with different labeled jobs. In separate trials, once-weekly semaglutide produced average weight loss of roughly 15 percent of body weight over 68 weeks in adults without diabetes, reported in a randomized trial published in a major medical journal, and tirzepatide reported larger figures again in its own phase 3 obesity trial. Those studies used different participants and designs, and there is no head-to-head trial against the oral combination, so treat cross-trial comparisons as direction rather than a ranking.
Weight-Loss Medication Options at a Glance
| Oral / Pill | Weekly Injection | |
|---|---|---|
| Naltrexone-bupropion ER | Daily tablet | - |
| Phentermine | Daily tablet (short-term) | - |
| Semaglutide | - | ~15% avg body weight loss over 68 wks |
| Tirzepatide | - | Largest avg loss reported in phase 3 |
As for the strongest weight-loss pill: there is no crown to hand out. Different oral options report different average results, side effect profiles differ sharply, and the one that works is the one a person can tolerate, afford and keep taking. If injectables are on your shortlist, the Semaglutide Uses And Safety page and the Tirzepatide Overview cover their own warnings, and Phentermine Weight Loss Basics covers the stimulant route. The full All Medication Guides index lists the rest.
Cost when you are paying yourself
Prices tracked on this site are US dollars per month, and two routes are kept separate. Cash pay is what a self-pay patient hands over. The with-insurance figure is the plan or membership fee only; copays and deductibles sit on top and vary by plan and state.
For programs that prescribe this combination, the range tracked here runs from to a month on a cash-pay basis. Those figures move, so read them as a live snapshot rather than a fixed number.
What drives the spread:
- Brand versus components. The approved product is a fixed-dose extended-release tablet. Separate naltrexone and bupropion tablets exist as their own approved products for other conditions, and prescribing them separately is an off-label approach, not the same medicine. Ask directly which one a program is dispensing.
- Pharmacy route. Mail-order fulfillment, retail pickup and manufacturer savings programs land at different totals.
- What the monthly fee includes. Some programs bundle the consultation, messaging and refills; others charge a membership plus the medicine separately.
- Intro versus renewal pricing. A low first month can step up at month two or three. Look for the renewal figure before you compare anything.
- Labs and follow-ups. Blood pressure checks and bloodwork may be included, extra, or left to your own clinician.
Because this is taken daily and long term, the annual figure tells you more than the monthly one:
What a year actually costs
Programmes quote a monthly headline. Add the medication, the labs and the renewal price and the real number is usually different.
Advertised prices change often and intro pricing rarely lasts. Ask what the renewal rate is before you commit to a plan.
On coverage, be careful with promises. Many US plans exclude weight-management drugs outright, and where they are covered, prior authorization and step therapy are common; denials for obesity medicines are routine rather than unusual. Health policy researchers at an independent US health policy organization track how patchy that coverage is. Call your plan, ask whether the specific product is on formulary, and ask what documentation a prior authorization needs. If you want a structured way to compare totals across programs, the Sample Savings Report shows the format, and the Patient Health Calculators handle the arithmetic.
How telehealth programs handle this prescription
Because this is an oral prescription with a boxed warning, the quality of the screening matters more than the slickness of the app. Programs differ in ways that are easy to check before you pay.
- Intake depth. A serious intake asks about seizures, eating disorders, opioid use, alcohol intake, bipolar disorder, glaucoma, blood pressure and every current medicine. A form that skips those is a red flag given the contraindication list.
- Who prescribes. Some programs name the clinician and their state license; others do not. Prescribing rules for telemedicine are set state by state, so licensure is not a detail.
- Monitoring plan. Ask how blood pressure and mood are followed, and who reviews the 12-week weight checkpoint.
- Pharmacy disclosure. Ask which pharmacy fills the order and whether the product is the approved fixed-dose tablet.
- Cancellation terms. Auto-renewing plans and multi-month prepayment are common. Read the terms before the first charge.
Telehealth Screening: What to Check Before You Pay
- Intake asks about seizures, eating disorders, opioid use, alcohol, bipolar disorder, glaucoma and blood pressure
- Prescribing clinician is named with a verifiable state license
- Monitoring plan covers blood pressure checks and the 12-week weight checkpoint
- Pharmacy discloses whether the product is the approved fixed-dose extended-release tablet
- Cancellation and renewal pricing terms are clear before the first charge
You can browse programs by condition and state in the Telehealth Provider Directory, see how provider pages are scored on the Provider Scoring Methodology page, and read cost and program analysis in the Weight Care Editorial Coverage. If you are also weighing injections, the ranked Compare GLP-1 Telehealth Programs guide covers the same decision points for that category.
Questions worth asking before the first prescription
Bring these to a consultation. They take five minutes and they surface most of the problems people run into later.
- Given my history and my me
