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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 opioid receptors, so opioid medicines may not work — and the label warns of a serious overdose risk in trying to override that.
The label says people taking Contrave may not fully benefit from opioid-containing medicines, including cough and cold remedies, antidiarrhoeal preparations and opioid analgesics. If intermittent opiate treatment is needed, it says Contrave should be temporarily discontinued and the opioid dose should not be raised above the standard dose. 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, or up to two weeks when coming off buprenorphine or methadone, to avoid precipitated withdrawal. 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, 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 discussConcomitant use of MAOIs and bupropion is contraindicated because of the risk of hypertensive reactions.
The label says bupropion inhibits the re-uptake of dopamine and norepinephrine, and can increase the risk of hypertensive reactions when used with other drugs that do the same, including MAOIs. It says at least 14 days should elapse between stopping an MAOI and starting Contrave, and at least 14 days after stopping Contrave before starting an MAOI. It also 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 inhibits CYP2D6 and can substantially raise the levels of medicines that depend on that enzyme.
The label reports that Contrave raised metoprolol exposure roughly four-fold and its peak concentration roughly two-fold compared with metoprolol alone, and that similar interactions have been seen with bupropion and desipramine or venlafaxine. It says coadministration with drugs metabolised by CYP2D6 — including certain antidepressants such as SSRIs and many tricyclics, antipsychotics such as haloperidol, risperidone and thioridazine, beta-blockers such as metoprolol, and Type 1C antiarrhythmics such as propafenone and flecainide — should be approached with caution and started 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, particularly where its therapeutic window 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, and contraindicates other bupropion-containing products outright.
The label says to use extreme caution when giving Contrave with other drugs that lower the seizure threshold, and names antipsychotics, antidepressants, theophylline and systemic corticosteroids as examples. It says to use low initial doses and increase gradually, and that concomitant use of other bupropion-containing products is contraindicated. The context is that the incidence of seizure with Contrave in clinical trials was about 0.1%, against 0% on placebo, and the label says the risk is dose-related. It also flags people with diabetes treated with insulin or oral medicines that can cause hypoglycaemia among those with predisposing factors.
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.
Bupropion is metabolised mainly by CYP2B6. The label says ticlopidine and clopidogrel increase bupropion exposure, and that during concomitant use the Contrave daily dose should not exceed two tablets — one each morning and evening. In the other direction, it says ritonavir, lopinavir and efavirenz decrease bupropion exposure and may reduce efficacy, and recommends avoiding concomitant use. Carbamazepine, phenobarbital and phenytoin are also listed as CYP2B6 inducers that may reduce efficacy.
Alcohol
The label asks you to minimise or avoid it — and warns about stopping it suddenly.
Alcohol
Use cautionRare reports of neuropsychiatric events or reduced alcohol tolerance with bupropion, and abruptly stopping heavy drinking is itself a seizure risk.
The label says that in postmarketing experience there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in people drinking alcohol during bupropion treatment, and that the consumption of alcohol during treatment with Contrave should be minimised or avoided. There is a second, less obvious point: Contrave is contraindicated in people undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates or antiepileptic drugs, because 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 have dopamine agonist effects, and that CNS toxicity has been reported when bupropion was given with levodopa or amantadine — restlessness, agitation, tremor, ataxia, gait disturbance, vertigo and dizziness. It says to use caution and monitor for these reactions. Separately, it says coadministration of Contrave with digoxin may decrease plasma digoxin levels, and that 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 that it should not be taken with a high-fat meal because of a resulting significant increase in bupropion and naltrexone systemic exposure. Avoiding high-fat meals appears again in the label list of measures for reducing seizure risk, alongside keeping the daily dose within four tablets, splitting it across two doses, escalating gradually, never taking more than two tablets at once, and waiting for the next scheduled dose if one is missed.
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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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