Bupropion Interactions: What You Need to Know

Bupropion is generally well-tolerated, but it interacts with a significant number of other medications. Some interactions are dangerous. Others just mean your doctor needs to adjust doses. Either way, knowing what interacts with Bupropion — and telling your doctor about everything you take — is essential for staying safe.

This guide covers the major and moderate drug interactions, supplements and over-the-counter medications to watch, and food and drink interactions.

How Drug Interactions Work with Bupropion

Bupropion interacts with other drugs in two main ways:

1. Bupropion affects other drugs: Bupropion is a strong inhibitor of the CYP2D6 enzyme in the liver. This enzyme is responsible for breaking down many common medications. When Bupropion blocks CYP2D6, those medications build up to higher-than-normal levels in your blood, which can increase their effects — and side effects.
2. Other drugs affect Bupropion: Bupropion is broken down by the CYP2B6 enzyme. Medications that inhibit or induce this enzyme can raise or lower Bupropion levels in your body.

Additionally, some interactions increase the risk of seizures — Bupropion's most serious dose-dependent side effect.

Major Drug Interactions (Avoid or Use Extreme Caution)

MAO Inhibitors — Contraindicated

Do not take Bupropion with or within 14 days of using a monoamine oxidase (MAO) inhibitor. This combination can cause a hypertensive crisis — a sudden, dangerous spike in blood pressure. MAO inhibitors include:

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Isocarboxazid (Marplan)
• Selegiline (Emsam) — the patch form at higher doses
• Linezolid (Zyvox) — an antibiotic with MAO-inhibiting properties
• Methylene Blue — when given intravenously

Drugs That Lower the Seizure Threshold

Because Bupropion already carries a dose-dependent seizure risk, combining it with other seizure-threshold-lowering drugs is particularly dangerous. These include:

• Other Bupropion-containing products (e.g., taking Wellbutrin and Zyban together — never do this)
• Antipsychotics — Haloperidol (Haldol), Risperidone (Risperdal), Chlorpromazine (Thorazine)
• Theophylline — Used for asthma
• Systemic corticosteroids — Prednisone, Dexamethasone
• Stimulants — Amphetamine (Adderall), Methylphenidate (Ritalin)
• Tramadol (Ultram) — A pain medication that also lowers seizure threshold
• Abrupt withdrawal from sedatives — Suddenly stopping alcohol, benzodiazepines (Xanax, Ativan, Valium), barbiturates, or antiepileptic drugs can lower seizure threshold

CYP2D6 Substrates (Bupropion Raises Their Levels)

Bupropion inhibits CYP2D6, which means it can increase blood levels of drugs metabolized by that enzyme. Your doctor may need to reduce the dose of:

• SSRIs: Paroxetine (Paxil), Fluoxetine (Prozac)
• Tricyclic antidepressants: Desipramine (Norpramin), Nortriptyline (Pamelor)
• Antipsychotics: Haloperidol (Haldol), Risperidone (Risperdal), Thioridazine
• Beta-blockers: Metoprolol (Lopressor, Toprol-XL)
• Type 1C antiarrhythmics: Flecainide (Tambocor), Propafenone (Rythmol)

Dopaminergic Drugs

Combining Bupropion with other dopamine-affecting medications can cause CNS toxicity (agitation, tremor, confusion). Use caution with:

• Levodopa — Used for Parkinson's disease
• Amantadine — Used for Parkinson's and influenza

Moderate Drug Interactions

These require monitoring but are not necessarily contraindicated:

• Digoxin (Lanoxin) — Bupropion may decrease Digoxin levels. Your doctor should monitor Digoxin blood levels.
• Cimetidine (Tagamet) — Can increase Bupropion levels. This is less common now since Cimetidine has been largely replaced by other acid reducers.
• Warfarin (Coumadin) — Bupropion may alter your INR (blood clotting measure). If you take Warfarin, your doctor should monitor your INR more frequently when starting or stopping Bupropion.
• Tamoxifen (Nolvadex) — This is an important one. Tamoxifen relies on CYP2D6 to convert it to its active form (Endoxifen). Bupropion inhibits CYP2D6, which may reduce Tamoxifen's effectiveness. If you're taking Tamoxifen for breast cancer, talk to your oncologist before starting Bupropion.

CYP2B6 Interactions (Drugs That Affect Bupropion Levels)

Some medications change how your body processes Bupropion:

CYP2B6 inhibitors (increase Bupropion levels):

• Ticlopidine (Ticlid)
• Clopidogrel (Plavix)

CYP2B6 inducers (decrease Bupropion levels, potentially reducing effectiveness):

• Ritonavir (Norvir), Lopinavir — HIV medications
• Efavirenz (Sustiva) — HIV medication
• Carbamazepine (Tegretol) — Anticonvulsant
• Phenytoin (Dilantin) — Anticonvulsant
• Phenobarbital — Anticonvulsant/sedative

Supplements and OTC Medications to Watch

Don't forget to tell your doctor about supplements and over-the-counter products. Some that interact with Bupropion:

• St. John's Wort — May increase serotonin and norepinephrine activity. Generally not recommended with any antidepressant.
• Melatonin — Generally safe, but may increase drowsiness/dizziness in combination.
• Pseudoephedrine (Sudafed) — A stimulant decongestant that could increase blood pressure and agitation when combined with Bupropion.
• Diphenhydramine (Benadryl) — Metabolized by CYP2D6; Bupropion may increase its effects and sedation.
• Dextromethorphan (in cough syrups) — Metabolized by CYP2D6. Bupropion can increase DXM levels. (Interestingly, this interaction is used therapeutically in the combination drug Auvelity.)

Food and Drink Interactions

Alcohol

Alcohol is the biggest concern. It lowers the seizure threshold, and combining it with Bupropion increases the risk of seizures. If you drink regularly and want to start Bupropion, be honest with your doctor. If you drink heavily, Bupropion may not be the right choice. At minimum, avoid excessive alcohol consumption while taking it.

If you're being told to stop drinking, do not stop abruptly without medical supervision — sudden alcohol withdrawal also lowers the seizure threshold and is dangerous with Bupropion.

Grapefruit

Grapefruit may slightly increase Bupropion levels, but this is considered a minor interaction. You don't need to eliminate grapefruit entirely, but avoid consuming large quantities regularly.

Food and Absorption

Bupropion can be taken with or without food. There are no significant food-absorption interactions.

What to Tell Your Doctor

Before starting Bupropion — and at every follow-up — make sure your doctor knows about:

• All prescription medications you take, including those from other doctors
• Over-the-counter medications — especially pain relievers, cold medicines, and sleep aids
• Supplements and herbal products — including vitamins, fish oil, and herbal teas
• Alcohol use — be honest about how much and how often
• Recreational drug use — stimulants and other substances can interact dangerously
• Any recent medication changes — especially stopping benzodiazepines, alcohol, or seizure medications

Bring a written list to your appointment. Pharmacists are also an excellent resource — they can run an interaction check on all your medications in seconds.

For more background on what Bupropion is and how it's used, read What Is Bupropion? For side effect details, see our Bupropion side effects guide.

Final Thoughts

Bupropion's drug interactions are manageable — but only if your doctor knows the full picture. The biggest risks come from MAO inhibitors (strictly contraindicated), seizure-threshold-lowering drugs, and alcohol. The CYP2D6 interactions are important too, especially if you take medications like Tamoxifen, Metoprolol, or Thioridazine.

Don't be afraid of drug interactions — be informed about them. The more you and your doctor communicate, the safer and more effective your treatment will be.

Already taking Bupropion and need a refill? Medfinder can help you find it in stock near you.