Contrave Dosing: The Full 4-Week Titration Schedule, Plus What To Do If You Miss a Dose

Key Takeaways

• Contrave is dosed by tablet count, not milligrams. Each tablet contains 8 mg naltrexone and 90 mg bupropion.
• The standard schedule starts at 1 tablet in the morning during week 1 and reaches 2 tablets twice daily (4 tablets total) in week 4.
• Slow titration exists for a reason: it lowers nausea risk and the chance of bupropion-related seizure.
• The maintenance dose is 4 tablets a day, taken as 2 in the morning and 2 in the evening, with food.
• Stop and call your provider if you have a seizure, severe mood changes, or signs of liver injury (yellowing of skin or eyes, dark urine, right-upper-belly pain).

Direct answer (40-60 words)

Contrave dosing follows a 4-week titration. Week 1 is 1 tablet in the morning. Week 2 is 1 tablet morning and 1 tablet evening. Week 3 is 2 tablets morning and 1 tablet evening. Week 4 onward is 2 tablets morning and 2 tablets evening. Each tablet contains 8 mg naltrexone plus 90 mg bupropion.

Table of contents

1. The 30-second answer
2. What's actually in a Contrave tablet
3. The 4-week titration schedule
4. Why the titration matters (nausea, seizure risk)
5. Maintenance dosing details
6. Missed doses and what to do
7. When to stop, slow down, or call your provider
8. Drug and food interactions to know
9. Comparing Contrave to GLP-1 weight-loss options
10. FAQ
11. Sources
12. Footer disclaimers

What's actually in a Contrave tablet

Contrave is a fixed-dose combination of two drugs that have been on the market separately for decades:

• Naltrexone 8 mg. An opioid receptor antagonist, originally approved to treat alcohol use disorder and opioid dependence at higher doses.
• Bupropion 90 mg. A norepinephrine-dopamine reuptake inhibitor, sold under other names for depression and smoking cessation.

The tablet is an extended-release formulation, which is why splitting or crushing is forbidden. Crushing a controlled-release tablet dumps the full dose at once and can spike bupropion plasma levels into the seizure-risk range.

The combination was approved by the FDA in September 2014 for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity, in adults with a BMI of 30 or higher, or 27 or higher with at least one weight-related comorbid condition (Greenway et al., Lancet 2010; FDA approval letter 2014).

The naltrexone half blocks compensatory opioid signaling in the hypothalamus that would otherwise blunt bupropion's appetite-suppressing effect. Together, the two drugs reduce food cravings and energy intake. They are not GLP-1 receptor agonists. They don't slow gastric emptying. The mechanism is centrally mediated, working in the brain.

The 4-week Contrave titration schedule

The label-recommended dose escalation is identical for every patient who starts Contrave (Apovian et al., Obesity 2013; package insert 2024).

Week	Morning dose	Evening dose	Total tablets/day	Total naltrexone	Total bupropion
Week 1	1 tablet	0 tablets	1	8 mg	90 mg
Week 2	1 tablet	1 tablet	2	16 mg	180 mg
Week 3	2 tablets	1 tablet	3	24 mg	270 mg
Week 4 onward	2 tablets	2 tablets	4	32 mg	360 mg

A few notes on the chart:

• The week 4 dose, 4 tablets a day, is the maintenance dose. There is no "higher" approved dose. If you don't lose at least 5% of baseline body weight by week 16, current label guidance is to discontinue rather than escalate.
• The split is uneven. Week 3 is 2 in the morning and 1 in the evening (not the reverse). This is intentional. Bupropion's stimulant-like effect is better tolerated earlier in the day and can disrupt sleep if the bigger dose lands at night.
• Patients with moderate hepatic impairment or renal impairment may need a reduced maximum (2 tablets a day total per the label). Severe hepatic impairment is a contraindication.

Why the titration matters

Two reasons.

Reason 1: nausea. Contrave's most common side effect is nausea, reported in roughly 32 to 34% of patients in the COR trials (Greenway et al., Lancet 2010; Apovian et al., Obesity 2013). Most of that nausea hits in the first 4 weeks and fades. Starting at 1 tablet and ramping slowly cuts the peak nausea intensity. Patients who try to skip ahead often quit by week 2.

Reason 2: seizure risk. Bupropion lowers the seizure threshold in a dose-dependent way. The Contrave label warns of a roughly 0.1% seizure rate at the 360 mg/day maintenance dose. Faster escalation, higher peak plasma levels, or co-administration with a high-fat meal (which roughly doubles bupropion AUC) all push that risk up. The titration is the primary tool the label uses to keep seizure risk near baseline.

The label also lists a number of conditions that are flat contraindications because of seizure risk:

• Seizure disorder of any kind, current or past
• Active or prior anorexia nervosa or bulimia nervosa
• Chronic opioid use (the naltrexone half can precipitate withdrawal)
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or anti-epileptic drugs
• Use of MAO inhibitors within the prior 14 days

If any of those apply to you, Contrave is not a safe option, regardless of how slow the titration is.

Maintenance dosing details

Once you reach 2 tablets twice daily, that's the dose you stay on as long as the medication is working. A few details that come up often:

Take with food, but not a high-fat meal. A high-fat meal increases bupropion's AUC by roughly 90% and seizure risk goes up with it (label, FDA 2014). A normal meal or light snack is fine and is what the trials used.

Don't double up. If you miss the morning dose, don't take 4 tablets in the evening. Skip the missed dose and go back to your normal schedule the next morning. Doubling up has the same problem as fast titration: a peak plasma level that crosses into seizure territory.

Don't split or crush tablets. Contrave is an extended-release formulation. Splitting it converts a 12-hour release profile into an immediate-release dose. The plasma curve flips from a smooth peak around 3 hours post-dose to a sharp spike, again pushing into seizure-risk levels.

Time the doses 8 hours apart. Most patients land on something like 8 a.m. and 4 p.m. or 9 a.m. and 5 p.m. The evening dose should ideally be before dinner so it's taken with food, not on a full or empty stomach late.

Stop after 16 weeks if not effective. The label criterion is at least 5% weight loss from baseline by week 16. If you haven't hit that, the data suggests Contrave isn't the right tool for you, and continuing exposes you to side-effect risk without the offsetting benefit.

What to do if you miss a dose

The simple rule: if you miss a dose, skip it. Don't take a make-up dose later in the day, and don't double up tomorrow.

If you miss multiple consecutive doses (more than 2 days off), restart from the beginning of the titration. Going from 0 back to the maintenance 4-tablet dose without a re-ramp would deliver a peak plasma bupropion level your body hasn't seen recently. The seizure risk goes up.

If you've missed a single dose, here's the cleaner version:

• Missed the morning dose, remember by lunch: skip it, take the evening dose at the normal time.
• Missed the morning dose, remember at 4 p.m.: skip it, take the evening dose at the normal time.
• Missed the evening dose, remember at bedtime: skip it. Don't take the dose late, especially not within 4 hours of bed (sleep interference).
• Missed both doses for the day: skip them, restart the next day at the normal schedule. If you've missed both for 2+ consecutive days, call your provider before restarting.

When to stop, slow down, or call your provider

Stop Contrave and call urgent care or 911 right away if you have:

• A seizure of any kind
• Suicidal thoughts, severe mood changes, or new or worsening depression
• Signs of liver injury: yellowing of skin or eyes, dark urine, severe right-upper-belly pain, persistent nausea
• A severe allergic reaction (face/lip/tongue swelling, difficulty breathing, rash with blistering)
• Chest pain, fast or irregular heartbeat with shortness of breath

Call your provider within a few days, but don't necessarily stop, if you have:

• Persistent nausea or vomiting beyond week 4
• Insomnia that doesn't resolve after the first 2 weeks
• Significant blood pressure increase (Contrave can raise BP by an average of 1 to 2 mmHg, more in some patients)
• Headache that's worse than your baseline
• Constipation or unusual bowel changes

A 2019 post-marketing FAERS analysis (FDA Adverse Event Reporting System) showed that the most common reasons patients discontinued Contrave were nausea (33%), headache (14%), and insomnia (10%). Most resolved with a slower titration or a temporary step-back to the prior week's dose.

If your provider agrees, stepping back one tablet for a week is reasonable when side effects are intolerable but not dangerous. Going from 4 tablets a day back to 3 tablets a day for a week, then re-attempting 4, is a common rescue.

Drug and food interactions to know

A short list of things that change Contrave dosing or safety:

MAO inhibitors. Absolute contraindication. Don't take Contrave within 14 days of stopping an MAOI.

Other bupropion products (other antidepressants or smoking-cessation products). Stacking is contraindicated. The total daily bupropion would exceed the 360 mg ceiling and seizure risk climbs sharply.

Opioid pain medications. The naltrexone half blocks opioid receptors. If you need an opioid for surgery or acute pain, Contrave needs to be paused. In an emergency, higher opioid doses are required to overcome the blockade and that's a hospital decision, not a self-managed one.

Alcohol. Reduce or stop. Bupropion plus alcohol raises seizure risk and worsens neuropsychiatric side effects. Sudden discontinuation of heavy alcohol use is also a seizure trigger.

CYP2D6 substrates (some SSRIs, beta-blockers, antiarrhythmics, antipsychotics). Bupropion inhibits CYP2D6. Doses of those medications often need to come down. Your prescriber and pharmacist will check for these.

Tobacco/nicotine products. Bupropion is also used for smoking cessation. Stacking nicotine replacement plus Contrave is fine, but doubling up on smoking-cessation bupropion isn't.

High-fat meals. Roughly double the bupropion AUC. Avoid taking Contrave with a heavy fried or fatty meal.

Grapefruit juice. Modest CYP3A4 inhibition. Not a strict contraindication, but worth flagging to your prescriber if you drink it daily.

Comparing Contrave to GLP-1 weight-loss options

Contrave isn't the only prescription weight-loss tool, and a question we hear often is how it stacks up against the GLP-1 receptor agonists (semaglutide, tirzepatide). The mechanisms are different and the results are different.

Feature	Contrave	Semaglutide 2.4 mg	Tirzepatide 15 mg
Drug class	Naltrexone + bupropion combo	GLP-1 receptor agonist	GLP-1 + GIP dual agonist
Route	Oral, twice daily	Once-weekly injection	Once-weekly injection
Average weight loss at 1 year	5 to 9% (Greenway et al., 2010; Apovian et al., 2013)	~14.9% (Wilding et al., NEJM 2021, STEP 1)	~20.9% (Jastreboff et al., NEJM 2022, SURMOUNT-1)
Most common side effect	Nausea, headache, insomnia	Nausea, vomiting	Nausea, vomiting
Seizure risk	Yes (low, ~0.1%)	No	No
Pregnancy safe	No	No	No

The honest read: GLP-1 medications produce more weight loss in head-to-head and indirect comparison data. Contrave works best for patients who can't or won't use injectable medications, who have specific food-craving patterns where the naltrexone-bupropion combination helps, or who need a less expensive oral option.

For more on the comparison, see our GLP-1 medications overview and the tirzepatide vs semaglutide comparison.

FAQ

What is the standard Contrave dose? Maintenance dose is 4 tablets a day, taken as 2 tablets in the morning and 2 in the evening, with food. Each tablet has 8 mg naltrexone and 90 mg bupropion, so the total daily dose is 32 mg naltrexone and 360 mg bupropion.

How long does the titration take? 4 weeks. Week 1 is 1 tablet, week 2 is 2, week 3 is 3, week 4 onward is 4. Most patients reach maintenance dose smoothly. A small number need to step back a week if nausea is intolerable.

Can I take Contrave at night only? No. Bupropion is stimulating for many patients and worsens insomnia if all of it lands in the evening. The label specifies twice-daily dosing with the morning dose at least as large as the evening dose.

Can I crush or split Contrave tablets? No. Contrave is extended-release. Crushing converts the 12-hour release into an immediate dose, spiking bupropion plasma levels into the seizure-risk range. Swallow whole.

What happens if I take Contrave with a high-fat meal? Bupropion AUC roughly doubles, and seizure risk goes up with it. Take Contrave with food, but not a heavy fatty meal. A normal-sized lunch or dinner is fine.

How much weight loss should I expect? In the COR trials, patients on full-dose Contrave plus lifestyle support lost an average of 5 to 9% of baseline body weight at 1 year, compared to about 1.4% on placebo (Apovian et al., Obesity 2013). Individual results vary based on diet, activity, and adherence.

What if I miss a dose? Skip it. Don't double up. If you miss multiple consecutive doses (over 2 days), call your provider before restarting at the maintenance dose. You may need to re-titrate from a lower starting point.

Can I drink alcohol on Contrave? Reducing or stopping is recommended. Alcohol plus bupropion raises seizure risk, worsens mood side effects, and abruptly stopping heavy drinking can itself trigger seizures. Talk to your prescriber.

Does Contrave interact with antidepressants? Many SSRIs are CYP2D6 substrates and Contrave inhibits CYP2D6, so dose adjustments may be needed. Stacking another bupropion-containing product is contraindicated. Always tell your prescriber every medication you take.

Is Contrave safe long-term? Trial data extends to about 56 weeks. There's no evidence of long-term harm at maintenance dose, but patients with cardiovascular risk should have blood pressure and heart rate monitored. Stop if you don't see at least 5% weight loss by week 16.

Can I take Contrave while pregnant? No. Contrave is contraindicated in pregnancy. Stop Contrave if you become pregnant or are trying to become pregnant.

Is Contrave the same as Wellbutrin? No. Wellbutrin is bupropion alone, in different formulations and at different daily totals. Contrave is bupropion plus naltrexone in a fixed combination, FDA-approved for weight management specifically. The two are not interchangeable.

Does Contrave cause weight loss without diet changes? A small amount, but the trial protocols all included a reduced-calorie diet and increased activity. The medication is approved as an adjunct to lifestyle change, not a stand-alone treatment.

Sources

1. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376:595-605.
2. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity. 2013;21:935-943.
3. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity. 2011;19:110-120.
4. Hollander P, Gupta AK, Plodkowski R, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36:4022-4029.
5. FDA. Contrave prescribing information. Approved September 2014; current label revision 2024.
6. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384:989-1002.
7. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022;387:205-216.
8. FDA Adverse Event Reporting System (FAERS) public dashboard, naltrexone-bupropion combination, accessed Q1 2026.

Footer disclaimers

Platform Disclaimer. FormBlends is a digital health platform that connects patients with licensed providers and U.S.-based pharmacies. We do not manufacture, prescribe, or dispense medication directly. All clinical decisions are made by independent licensed providers.

Compounded Medication Notice. Compounded semaglutide and tirzepatide are not FDA-approved. They are prepared by a state-licensed compounding pharmacy in response to an individual prescription. Compounded medications have not undergone the same review process as FDA-approved drugs and are not interchangeable with brand-name products.

Results Disclaimer. Individual results vary. Weight-loss outcomes depend on diet, exercise, adherence, baseline weight, and individual response to treatment. Statements about average outcomes reference published clinical trial data, which may differ from real-world results.

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