Contrave (naltrexone/bupropion): how it works and its warnings

Key takeaways

• Contrave combines naltrexone and bupropion and is FDA approved for long-term weight management in adults with obesity, or overweight plus a weight-related condition.^[1]
• In the COR trials, average weight loss at 56 weeks was 3.7% to 8.1% with Contrave vs 1.3% to 4.9% with placebo; the label says to stop if less than 5% is lost after 12 weeks at the full dose.^[1]
• It carries a boxed warning about suicidal thoughts and behaviors because of its bupropion component; mood changes need prompt attention.^[1]
• It is not for people with uncontrolled high blood pressure, seizures, eating disorders, chronic opioid use or other bupropion products, and it has many drug interactions.^[1]
• The manufacturer listed $99 or less per month through CurAccess and $199 for 120 tablets with the savings card at retail (checked 2026-10-06).^[4]

In short: Contrave is an extended-release tablet that combines naltrexone (an opioid blocker) and bupropion (an ingredient also used in some antidepressants). It has been FDA approved since September 10, 2014, together with a reduced-calorie diet and more physical activity, for long-term weight management in adults with obesity, or with overweight and at least one weight-related condition. It carries a boxed warning about suicidal thoughts and behaviors because of its bupropion component, and it is not for people with uncontrolled high blood pressure, seizures, eating disorders or chronic opioid use (label checked on DailyMed on 2026-10-06).

Contrave works differently from GLP-1 medicines: it acts on the brain’s appetite and reward systems rather than on gut hormones, which is why some people and clinicians consider it when cravings play a big role. This page explains what the official prescribing information says about how it works, who it is for, what the trials showed, the side effects and warnings, the many interactions to check, and what it costs. It is general education, not personal medical advice. Please research your options, talk with a licensed doctor and get a full evaluation, including a blood pressure check and a review of every medicine you take, before considering it.

What Contrave is and how it works

Each Contrave tablet contains 8 mg of naltrexone hydrochloride and 90 mg of bupropion hydrochloride in an extended-release form. The label explains the two parts:

• Bupropion is a relatively weak blocker of the reuptake of dopamine and norepinephrine, two brain messengers. It is the same ingredient as some antidepressants and a smoking-cessation medicine, though Contrave is not approved for either use.
• Naltrexone blocks opioid receptors. On its own, it is used for alcohol and opioid dependence.

According to the label, animal studies suggest the combination works on two areas of the brain involved in eating: the hypothalamus, which regulates appetite, and the mesolimbic dopamine circuit, the brain’s reward system. In laboratory studies, the pair increased the activity of appetite-regulating POMC neurons and reduced food intake when delivered to a reward area in mice. The label is careful to say that the exact effects leading to weight loss “are not fully understood.” Our guide to appetite suppressants explains how this compares with stimulant-type medicines such as phentermine.

FDA status and who it is labeled for

Drugs@FDA lists the original approval on September 10, 2014, as a new combination product (NDA 200063). The label covers adults with obesity, or with overweight and at least one weight-related condition, alongside a reduced-calorie diet and more physical activity. The trials enrolled adults with a BMI of 30 or more, or 27 or more with high blood pressure, high cholesterol or type 2 diabetes. It is not approved for anyone under 18. The label also states two limits: its effect on heart attacks, strokes and deaths “has not been established,” and it should not be combined with other naltrexone products or with any other bupropion product. Our BMI calculator can show where you stand, but whether Contrave fits you is a decision for you and your clinician.

Boxed warning: suicidal thoughts and behaviors

For context, the label notes that in the Contrave obesity trials of up to 56 weeks there were no suicides or suicide attempts, and suicidal ideation was reported by 1 of 3,239 people on Contrave (0.03%) and 3 of 1,515 on placebo (0.20%). The boxed warning applies because the evidence on antidepressants in younger people is the standard for every bupropion product. In the one-year trials, psychiatric and sleep-related side effects overall were more common on Contrave (22.2%) than placebo (15.5%), mainly sleep problems.

Who should not take Contrave

The label lists these contraindications:

• Uncontrolled high blood pressure
• A seizure disorder or a history of seizures
• A current or past diagnosis of bulimia or anorexia nervosa, which raises seizure risk
• Using any other bupropion product (for example Wellbutrin, Aplenzin or Zyban)
• Chronic opioid or opiate use (including methadone and buprenorphine), or acute opiate withdrawal
• Abruptly stopping alcohol, benzodiazepines, barbiturates or antiseizure medicines
• Taking an MAOI, or within 14 days of stopping one (including linezolid or intravenous methylene blue)
• A known allergy to bupropion, naltrexone or any ingredient

The label also advises screening for bipolar disorder before starting, extra caution in people with seizure risk factors (such as head injury, heavy alcohol use or diabetes treated with insulin or sulfonylureas), dose limits with moderate or severe kidney or moderate liver impairment, and avoiding it in end-stage kidney disease or severe liver impairment.

How it is taken, in general

If a dose is missed, the label says to wait for the next scheduled dose rather than doubling up. Your prescriber sets the schedule, which may be lower with kidney or liver problems or with certain other medicines; never change it on your own.

What the trials showed

Four 56-week trials (COR-I, COR-II, COR-BMOD and COR-Diabetes) enrolled 4,536 adults. On average, participants were 46 years old with a BMI of 36, and 83% were women. COR-I and COR-II added a diet of about 500 fewer calories a day with counseling; COR-BMOD added an intensive behavior program of 28 group sessions; COR-Diabetes enrolled people with type 2 diabetes.

• Placebo
• Contrave

COR-I (diet and counseling)1.3%5.4%

COR-BMOD (intensive behavior program)4.9%8.1%

COR-Diabetes (type 2 diabetes)1.7%3.7%

Average weight loss at 56 weeks in the Contrave trials

Item	Placebo	Contrave
COR-I (diet and counseling)	1.3%	5.4%
COR-BMOD (intensive behavior program)	4.9%	8.1%
COR-Diabetes (type 2 diabetes)	1.7%	3.7%

Least-squares mean percent change from baseline, last observation carried forward. About 45% of participants in both groups left the trials before week 56.

Source: Contrave prescribing information, Table 6 (DailyMed) (checked on October 6, 2026)

• Placebo
• Contrave

COR-I, 5% or more17%42%

COR-I, 10% or more7%21%

COR-BMOD, 5% or more43%57%

COR-BMOD, 10% or more21%35%

COR-Diabetes, 5% or more18%36%

COR-Diabetes, 10% or more5%15%

Share who lost at least 5% and at least 10% of body weight (56 weeks)

Item	Placebo	Contrave
COR-I, 5% or more	17%	42%
COR-I, 10% or more	7%	21%
COR-BMOD, 5% or more	43%	57%
COR-BMOD, 10% or more	21%	35%
COR-Diabetes, 5% or more	18%	36%
COR-Diabetes, 10% or more	5%	15%

Source: Contrave prescribing information, Table 6 (DailyMed) (checked on October 6, 2026)

Two patterns stand out. First, results were best when the medicine was combined with an intensive behavior program (COR-BMOD), which also helped the placebo group. Second, dropout was high: about 45% of participants left before the end, most in the first 12 weeks, and 24% on Contrave versus 12% on placebo stopped because of side effects. In a body-composition substudy, fat mass fell by 4.7 kg on Contrave versus 1.4 kg on placebo. In COR-I, waist size fell by 6.2 cm versus 2.5 cm, and HDL (“good”) cholesterol rose by 8.0% versus 0.8%; in COR-Diabetes, HbA1c fell by 0.6 points versus 0.1.

For perspective, these average losses are smaller than those seen with GLP-1 medicines such as Wegovy and Zepbound in their own trials, though trials of different drugs are not directly comparable. The American Gastroenterological Association’s 2022 guideline suggested naltrexone-bupropion as one of several options for long-term weight management, based on moderate-certainty evidence.

Side effects

• Placebo
• Contrave

Nausea6.7%32.5%

Constipation7.2%19.2%

Headache10.4%17.6%

Vomiting2.9%10.7%

Dizziness3.4%9.9%

Insomnia5.9%9.2%

Dry mouth2.3%8.1%

Diarrhea5.2%7.1%

Most common side effects with Contrave

Item	Placebo	Contrave
Nausea	6.7%	32.5%
Constipation	7.2%	19.2%
Headache	10.4%	17.6%
Vomiting	2.9%	10.7%
Dizziness	3.4%	9.9%
Insomnia	5.9%	9.2%
Dry mouth	2.3%	8.1%
Diarrhea	5.2%	7.1%

2,545 adults on Contrave and 1,515 on placebo in placebo-controlled trials up to 56 weeks.

Source: Contrave prescribing information, Table 3 (DailyMed) (checked on October 6, 2026)

Nausea was the most common reason for stopping (6.3%), followed by headache (1.7%) and vomiting (1.1%). Other side effects in at least 2% of people include anxiety, hot flushes, tiredness, tremor, ringing in the ears (tinnitus), upper abdominal pain, sweating, irritability, raised blood pressure, taste changes and palpitations. Dizziness-type events were more common (10.6% vs 3.6%), as were problems with attention (2.5% vs 0.6%). People 65 and older in the trials had more psychiatric and sleep side effects, though the group was small.

Serious risks

• Seizures. Bupropion can cause seizures; the risk is dose related. In trials, seizures occurred in about 0.1% on Contrave versus 0% on placebo. Following the dosing rules, avoiding high-fat meals and never taking extra tablets lower the risk. Anyone who has a seizure should stop and not restart.
• Opioid overdose and withdrawal. Because naltrexone blocks opioids, pain medicines may not work, and trying to overcome the block with large opioid doses can cause a fatal overdose. After stopping Contrave, people may be more sensitive to opioids. The label says Contrave should be temporarily stopped when short-term opioid treatment is needed, for example around surgery; tell every clinician you take it.
• Raised blood pressure and heart rate, especially in the first 12 weeks. Blood-pressure-related side effects occurred in 6.3% versus 4.2%, and in 12.0% versus 6.5% in the diabetes trial. People with a recent heart attack or stroke, serious arrhythmias or heart failure were excluded from the trials.
• Neuropsychiatric effects (mood changes, agitation, hallucinations and others) have been reported with bupropion, mostly in smoking-cessation use; stop and call your clinician if they occur. Mania can be triggered in people with bipolar disorder.
• Liver injury has been seen with naltrexone; stop and seek care if you notice signs of hepatitis.
• Angle-closure glaucoma in people with narrow eye angles; serious allergic and skin reactions; and low blood sugar in people with diabetes on insulin or sulfonylureas as they lose weight.

Interactions to check

Contrave has more interactions than most weight-loss medicines, so a pharmacist review is especially important. The label highlights: MAOIs (contraindicated); opioids (blocked, and dangerous to override); medicines broken down by the liver enzyme CYP2D6, because bupropion raises their levels, including many antidepressants, some antipsychotics, metoprolol and certain heart-rhythm drugs; CYP2B6 inhibitors such as clopidogrel or ticlopidine, which limit the Contrave dose; CYP2B6 inducers such as ritonavir, efavirenz, carbamazepine, phenobarbital and phenytoin, which should be avoided; medicines that lower the seizure threshold; digoxin; levodopa and amantadine; and alcohol, which should be minimized or avoided. Bring a full list of every prescription, over-the-counter medicine and supplement to your appointment.

Pregnancy and breastfeeding

The label states that weight loss offers no benefit during pregnancy and may cause fetal harm, so Contrave should be stopped when a pregnancy is recognized. Available data on the individual ingredients have not shown a clear risk of major birth defects, but studies of bupropion and certain heart defects are inconsistent. Bupropion, naltrexone and their breakdown products pass into breast milk, and seizures have been reported in breastfed infants, although a link is unclear. Discuss pregnancy plans and breastfeeding with your clinician.

Cost and insurance

Prices from the manufacturer’s site, checked on 2026-10-06: through the CurAccess patient support program (home delivery from a partner pharmacy), Contrave is $99 or less per month; the site says patients in federal programs such as Medicaid, Medicare Part D and TRICARE are eligible for that program, with the purchase treated as a cash sale outside their insurance. At retail pharmacies, the Contrave Savings Card lowers the cost to as little as $0 for people with private insurance that covers it, and to $199 for 120 tablets for cash-paying patients; the card cannot be used by Medicaid beneficiaries. The manufacturer also offers an online consultation with a $45 fee if Contrave is prescribed. No generic version was listed when we checked.

$199Retail cash with savings card (120 tablets)

$99CurAccess home delivery (per month, up to)

$0Private insurance that covers it, with savings card (as low as)

Contrave monthly price options from the manufacturer

Item	Value
Retail cash with savings card (120 tablets)	$199
CurAccess home delivery (per month, up to)	$99
Private insurance that covers it, with savings card (as low as)	$0

Eligibility rules apply; the savings card cannot be used by Medicaid beneficiaries. 120 tablets is about a month at the full label dose.

Source: Contrave savings page (Currax Pharmaceuticals) (checked on October 6, 2026)

Medicare is prohibited by law from covering drugs used specifically for weight loss, and Contrave is not part of the 2026-2027 Medicare GLP-1 Bridge. Commercial coverage varies widely. Our insurance guide and the weight-loss costs hub explain what is usually covered and how to appeal a denial.

Alternatives and comparisons

Contrave is often weighed against Qsymia, the other combination pill; see Contrave vs Qsymia for a side-by-side view. Other approved options include orlistat, short-term phentermine, daily GLP-1 pills such as the Wegovy pill, and weekly injections. Our weight-loss pills guide ranks pills by evidence and the medications hub lists every option with its FDA status. If emotional eating or cravings are a big part of your story, emotional eating covers non-drug strategies that work well alongside any medicine, and the basics in how to lose weight stay the foundation.

FDA status and approved uses

Indication	Labeled population	For weight	Approved	Source
Reduce excess body weight and maintain weight reduction long term, with a reduced-calorie diet and increased physical activity	Adults with obesity, or overweight in the presence of at least one weight-related comorbid condition	Yes	September 10, 2014	Source

From the FDA label. Who a medicine is labeled for is not the same as whether it fits you; only a clinician can decide that.

How it is taken (in general)

Extended-release tablets taken in the morning and evening. The dose is increased over about 3 weeks from one tablet a day to the maintenance dose reached at week 4; higher daily doses are not recommended. Swallow whole; avoid high-fat meals. Evaluate after 12 weeks at maintenance and stop if less than 5% weight loss. Lower maximum with moderate/severe kidney, moderate liver impairment or CYP2B6 inhibitors. Follow your prescriber.

This is what the label describes in general, never a personal dose or schedule. Follow your prescriber.

What studies showed

Trial	Population	Duration	Outcome as reported
COR-I	Adults with obesity or overweight with hypertension or dyslipidemia	56 weeks	Weight -5.4% vs -1.3% with placebo; 42% vs 17% lost 5% or more.[1]
COR-BMOD	Adults in an intensive behavior modification program	56 weeks	Weight -8.1% vs -4.9%; 57% vs 43% lost 5% or more.[1]
COR-Diabetes	Adults with type 2 diabetes and BMI over 27	56 weeks	Weight -3.7% vs -1.7%; HbA1c -0.6 vs -0.1.[1]

Average results from trials; individual results vary. Results from different trials cannot be compared directly.

Side effects

Common side effect	How often (label)
Nausea	32.5% vs 6.7% placebo
Constipation	19.2% vs 7.2% placebo
Headache	17.6% vs 10.4% placebo
Vomiting	10.7% vs 2.9% placebo
Dizziness	9.9% vs 3.4% placebo
Insomnia	9.2% vs 5.9% placebo
Dry mouth	8.1% vs 2.3% placebo
Diarrhea	7.1% vs 5.2% placebo

Serious risks

• Suicidal thoughts and behaviors (boxed warning)
• Neuropsychiatric adverse events
• Seizures
• Vulnerability to opioid overdose and precipitated opioid withdrawal
• Increase in blood pressure and heart rate
• Allergic reactions, including Stevens-Johnson syndrome
• Hepatotoxicity
• Activation of mania
• Angle-closure glaucoma
• Hypoglycemia in type 2 diabetes on insulin or secretagogues

Warnings and who should not use it

Boxed warning

Suicidal thoughts and behaviors: Contrave contains bupropion, the active ingredient of some antidepressants. Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents and young adults in short-term trials. Monitor all patients for worsening and emergence of suicidal thoughts and behaviors. Contrave is not approved for use in pediatric patients.

Who should not use it (per the label)

• Uncontrolled hypertension
• Seizure disorder or a history of seizures
• Use of other bupropion-containing products
• Bulimia or anorexia nervosa
• Chronic opioid or opiate agonist (e.g., methadone) or partial agonist (e.g., buprenorphine) use, or acute opiate withdrawal
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates or antiepileptic drugs
• Use of MAOIs or within 14 days of stopping (including linezolid or IV methylene blue)
• Known allergy to bupropion, naltrexone or any component

Interactions, pregnancy and breastfeeding

Drug or class	What the label says
MAOIs	Contraindicated; increased risk of hypertensive reactions.
Opioid analgesics	Naltrexone blocks opioids; contraindicated with chronic opioid use; pause for intermittent opioid treatment.
Drugs metabolized by CYP2D6 (many antidepressants, antipsychotics, metoprolol, type 1C antiarrhythmics)	Bupropion inhibits CYP2D6 and can raise their levels; dose reduction may be needed.
CYP2B6 inhibitors (ticlopidine, clopidogrel)	Raise bupropion exposure; do not exceed one tablet twice daily.
CYP2B6 inducers (ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin)	May reduce efficacy; avoid.
Drugs that lower seizure threshold	Use with caution.
Digoxin	May decrease digoxin levels; monitor.
Levodopa and amantadine	Interaction listed on the label; use with caution.
Alcohol	Minimize or avoid; abrupt stopping of heavy use is a contraindication.

Pregnancy and breastfeeding

Weight loss offers no benefit to a pregnant patient and may cause fetal harm; discontinue when pregnancy is recognized. Data on the components have not shown a drug-associated risk of major birth defects; studies of bupropion and specific heart defects are inconsistent. Bupropion and naltrexone are present in human milk; seizures have been reported in breastfed infants (relationship unclear).

Cost, insurance and savings

Price	Amount	Basis	Checked on
Self-pay / cash	99 USD	per month or less, CurAccess home delivery (manufacturer program)	October 6, 2026
Self-pay / cash	199 USD	120 tablets at retail with the Contrave Savings Card, cash-paying patients	October 6, 2026
With savings program	0 USD	as low as, with private insurance that covers Contrave and the savings card (not for Medicaid beneficiaries)	October 6, 2026

Prices change often and depend on pharmacy, plan and location. Insurance can change what you pay. Every price shows the date we checked it.

Savings programs

• CurAccess Patient Support Program: $99 or less per month with home delivery; federal program enrollees eligible as cash purchases (checked October 6, 2026)
• Contrave Savings Card: Retail pharmacies; not for Medicaid beneficiaries (checked October 6, 2026)

Questions to ask your doctor or pharmacist

• Given my mood history, blood pressure and any seizure risk, is Contrave a safe option for me?
• Do any of my medicines, including antidepressants, heart medicines, clopidogrel or pain medicines, interact with it?
• What should I do if I need surgery or opioid pain relief while taking it?
• How will we judge at 12 weeks whether it is working, and what is the next step if it is not?
• How does it compare with Qsymia or a GLP-1 medicine for my goals and budget?

Frequently asked questions

How much weight do people lose on Contrave?

In the 56-week trials, average weight loss ranged from 3.7% (people with type 2 diabetes) to 8.1% (with an intensive behavior program), vs 1.3% to 4.9% on placebo. In COR-I, 42% lost at least 5% of their weight vs 17% on placebo.

How does Contrave work?

Naltrexone blocks opioid receptors and bupropion affects dopamine and norepinephrine. Animal studies suggest the pair acts on the brain's appetite center and reward system; the label says the exact mechanism is not fully understood.

Why does Contrave have a boxed warning?

Because it contains bupropion, an antidepressant ingredient. Antidepressants increased suicidal thoughts and behavior in young people in short-term trials, so all patients should be watched for mood changes. In the Contrave obesity trials, there were no suicides or attempts.

Can I take Contrave if I take opioid pain medicine?

Not with chronic opioid use: it is contraindicated. Naltrexone blocks opioids, and trying to overcome the block is dangerous. If short-term opioids are needed, the label says Contrave should be paused. Always tell clinicians you take it.

Can I drink alcohol on Contrave?

The label advises minimizing or avoiding alcohol, and it is contraindicated for people who are abruptly stopping heavy alcohol use because of seizure risk. Discuss your drinking honestly with your clinician.

Does Contrave raise blood pressure?

It can raise blood pressure and heart rate, especially in the first 12 weeks. It is contraindicated with uncontrolled high blood pressure, and blood pressure and pulse should be checked before and during treatment.

What are the most common side effects of Contrave?

Nausea (32.5% vs 6.7% on placebo), constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea. Nausea was the most common reason people stopped.

How much does Contrave cost?

On 2026-10-06 the manufacturer listed $99 or less per month through its CurAccess home-delivery program, and $199 for 120 tablets with its savings card at retail for cash-paying patients; as low as $0 with private insurance that covers it.

Is there a generic Contrave?

No generic naltrexone-bupropion extended-release product was listed when we checked on 2026-10-06. Taking separate naltrexone and bupropion products is not the same as the approved combination and should only be discussed with a clinician.

Official sources

• Prescribing information (FDA label)
• FDA approval letter or page
• Manufacturer information

References

1. CONTRAVE (naltrexone HCl and bupropion HCl) extended-release tablets: prescribing information. Nalpropion Pharmaceuticals, via DailyMed, 2025. (accessed October 6, 2026) Drug label
2. Drugs@FDA: Contrave, NDA 200063 (original approval 2014-09-10). U.S. Food and Drug Administration. (accessed October 6, 2026) Government page
3. Grunvald E, Shah R, Hernaez R, et al.. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology, 2022. doi:10.1053/j.gastro.2022.08.045 · PMID 36273831 (accessed October 6, 2026) Guideline
4. Contrave savings and CurAccess pharmacy. Currax Pharmaceuticals. (accessed October 6, 2026) Other
5. Medicare GLP-1 Bridge: information for providers. Centers for Medicare and Medicaid Services. (accessed October 7, 2026) Government page
6. A New Use for Wegovy Opens the Door to Medicare Coverage for Millions of People with Obesity. KFF, 2024. (accessed October 6, 2026) Other
7. Prescription Medications to Treat Overweight & Obesity. National Institute of Diabetes and Digestive and Kidney Diseases (NIH). (accessed October 7, 2026) Government page
8. 988 Suicide and Crisis Lifeline. 988 Lifeline. (accessed October 6, 2026) Other

Facts checked on October 6, 2026

Educational information, not medical advice. Talk with a qualified healthcare professional about your own situation. In an emergency call 911.