Quick reference
Scan this table first. Details for each row are below.
| What you're taking | Level | Short version |
|---|---|---|
| MAOIs | Contraindicated | Hypertensive reactions — 14-day gap either side |
| Opioid medicines | Contraindicated in chronic use | Naltrexone blocks them; overdose risk if you push through |
| CYP2D6 substrates | Caution | Bupropion raises their levels — start low, consider reducing |
| Seizure-threshold drugs | Extreme caution | Other bupropion products are contraindicated |
| Clopidogrel or ticlopidine | Caution | Cap Contrave at two tablets a day |
| Ritonavir, lopinavir, efavirenz | Caution | May reduce efficacy — the label says avoid |
| Alcohol | Caution | Minimise or avoid; stopping abruptly raises seizure risk |
| Levodopa or amantadine | Caution | CNS toxicity has been reported |
| Digoxin | Monitoring matters | Plasma digoxin levels may fall — monitor |
| High-fat meals | Avoid | Significantly raises exposure to both ingredients |
Opioid medicines
This is the interaction that changes how you use urgent care, dentistry and pain relief.
Opioid analgesics, cough and cold remedies, antidiarrhoeals
Avoid or discussNaltrexone blocks the receptors that opioids act on, so opioid medicines may not work. The label warns of a serious overdose risk in trying to override that.
The label says people taking Contrave may not fully benefit from medicines that contain an opioid. That includes cough and cold remedies, antidiarrhoeal preparations and opioid painkillers. If opioid treatment is needed now and then, the label says Contrave should be stopped for the time being. It says the opioid dose should not be raised above the standard dose. And it says Contrave should not be given to people on chronic opioids at all. Before starting, anyone who has been opioid-dependent — including on tramadol — should be opioid-free for at least 7 to 10 days. Coming off buprenorphine or methadone, that gap can be up to two weeks. The label's reason for the gap is to avoid withdrawal being triggered suddenly. The label is blunt about the danger of trying to overcome the blockade with large amounts of opioids. It says this may lead to a fatal overdose or life-threatening opioid intoxication. It also says sensitivity to opioids is raised after stopping Contrave. The same goes for when the next dose is due, and if a dose is missed.
MAOIs
A contraindication, with a two-week gap in both directions.
Monoamine oxidase inhibitors
Avoid or discussThe label says MAOIs and bupropion must not be taken together, because of the risk of hypertensive reactions — sharp rises in blood pressure.
MAOIs are an older type of antidepressant. The label says bupropion blocks the re-uptake of dopamine and norepinephrine, two of the brain messenger chemicals. Used with other drugs that do the same, including MAOIs, it can increase the risk of hypertensive reactions. The label says at least 14 days should elapse between stopping an MAOI and starting Contrave. It says at least 14 days should also pass after stopping Contrave before an MAOI is started. It notes that animal studies show the acute toxicity of bupropion is enhanced by the MAOI phenelzine.
Medicines processed by CYP2D6
A long list, and it includes several very common prescriptions.
Antidepressants, antipsychotics, beta-blockers and Type 1C antiarrhythmics
Use cautionBupropion blocks a liver enzyme called CYP2D6. That can substantially raise the levels of medicines the body clears using it.
CYP2D6 is one of the liver enzymes that clear medicines out of the body, and bupropion blocks it. The label reports that Contrave raised metoprolol exposure roughly four-fold. Its peak concentration rose roughly two-fold, compared with metoprolol alone. It says similar interactions have been seen with bupropion and desipramine or venlafaxine. Many common medicines are cleared by CYP2D6. They include certain antidepressants, such as SSRIs and many tricyclics, and antipsychotics such as haloperidol, risperidone and thioridazine. They also include beta-blockers such as metoprolol, and Type 1C antiarrhythmics such as propafenone and flecainide. The label says taking those alongside Contrave should be approached with caution. It says to start at the lower end of the other drug dose range. If Contrave is added for someone already on such a medicine, the label says to consider reducing that medicine dose. That matters most where the gap between too little and too much is narrow.
Drugs that lower the seizure threshold
Bupropion can cause seizures, so anything that adds to that risk matters.
Antipsychotics, antidepressants, theophylline, systemic corticosteroids
Avoid or discussThe label calls for extreme caution. It rules out other bupropion-containing products outright.
Some medicines lower the seizure threshold — they make a seizure more likely. The label says to use extreme caution when giving Contrave with them, and names antipsychotics, antidepressants, theophylline and systemic corticosteroids as examples. It says to use low initial doses and increase gradually. It also says other bupropion-containing products must not be taken alongside Contrave. For context: seizures happened in about 0.1% of people on Contrave in clinical trials, against 0% on placebo. The label says the risk is dose-related. It also lists factors that make a seizure more likely. Among them are diabetes treated with insulin, or with oral medicines that can cause hypoglycaemia.
Medicines that change bupropion levels
These work in both directions — some raise bupropion, others make Contrave less effective.
CYP2B6 inhibitors and inducers
Use cautionClopidogrel and ticlopidine cap the dose at two tablets a day. Ritonavir, lopinavir and efavirenz should be avoided.
The body clears bupropion mainly through a liver enzyme called CYP2B6. The label says ticlopidine and clopidogrel increase bupropion exposure. While either is being taken, it says the Contrave daily dose should not exceed two tablets. That is one each morning and one each evening. In the other direction, it says ritonavir, lopinavir and efavirenz decrease bupropion exposure. That may make Contrave less effective, and the label recommends avoiding those combinations. Carbamazepine, phenobarbital and phenytoin are also listed as speeding that enzyme up. They too may make it less effective.
Alcohol
The label asks you to minimise or avoid it — and warns about stopping it suddenly.
Alcohol
Use cautionThere are rare reports of neuropsychiatric events, or of reduced alcohol tolerance, with bupropion. And stopping heavy drinking abruptly is itself a seizure risk.
The label says that since bupropion went on the market, there have been rare reports from people drinking alcohol during treatment. Those reports are of adverse neuropsychiatric events, or of reduced alcohol tolerance. Neuropsychiatric here means effects on the brain, on mood or on behaviour. The label says the consumption of alcohol during treatment with Contrave should be minimised or avoided. There is a second, less obvious point. Contrave must not be taken by anyone who is abruptly stopping alcohol, benzodiazepines, barbiturates or antiepileptic drugs. That withdrawal raises seizure risk. The Medication Guide says that if you drink a lot of alcohol, you should talk with your healthcare provider before suddenly stopping.
Levodopa, amantadine and digoxin
Three named medicines with their own specific notes in the label.
Levodopa, amantadine and digoxin
Use cautionCNS toxicity has been reported with levodopa or amantadine; digoxin levels may fall.
The label says bupropion, levodopa and amantadine all act on dopamine, one of the brain messenger chemicals. CNS toxicity means harmful effects on the brain and nervous system. The label says it has been reported when bupropion was given with levodopa or amantadine. The effects reported were restlessness, agitation, tremor, ataxia (unsteady movement), gait disturbance (trouble walking), vertigo and dizziness. The label says to use caution and monitor for these reactions. Separately, it says taking Contrave with digoxin may decrease plasma digoxin levels. It says digoxin levels should be monitored in people taking both.
High-fat meals
The one food interaction, and the label ties it directly to seizure risk.
High-fat meals
Avoid or discussA high-fat meal significantly increases how much bupropion and naltrexone reach the bloodstream.
The label says that in clinical trials Contrave was administered with meals. But it says Contrave should not be taken with a high-fat meal. That significantly increases how much bupropion and naltrexone reach the bloodstream. Avoiding high-fat meals appears again in the label list of measures for reducing seizure risk. The rest of that list: keep the daily dose within four tablets, split it across two doses, and build the dose up gradually. It also says never to take more than two tablets at once, and to wait for the next scheduled dose if one is missed.
Urine drug screening
Contrave can cause a false positive for amphetamines
The label says false-positive urine immunoassay screening tests for amphetamines have been reported in people taking bupropion. That is because some screening tests are not specific enough to tell the two apart. The label says false positives may occur even after bupropion has been stopped. A confirmatory test, such as gas chromatography/mass spectrometry, does distinguish bupropion from amphetamines. The Medication Guide advises telling whoever is administering the test that you take Contrave, so a more specific test can be used.
Common questions
Written and maintained by one person · Built with agentic AI tools · Every number checked against the cited trial · Not medical advice
- Contrave (naltrexone and bupropion) prescribing information — Drug Interactions (7.1–7.8), Contraindications (4), Warnings and Precautions (5.3, 5.4, 5.5), Dosage and Administration (2.1, 2.4, 2.5), Medication Guide View source ↗
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