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Rx pill bottle and prescription pad: Bupropion interactions
Drug Info

Bupropion interactions to avoid

Bupropion interacts with other antidepressants, alcohol, caffeine, and other substances
Karen Berger medical writer and reviewer headshot
By | Sep. 30, 2023

Bupropion (Wellbutrin XL, Wellbutrin SR, Aplenzin, Forfivo XL) is a norepinephrine-dopamine reuptake inhibitor (NDRI) that treats major depressive disorder, prevents seasonal affective disorder, and helps people stop smoking. Bupropion interacts with antidepressants, drugs that increase the risk of seizures, and drugs that increase dopamine. It also interacts with alcohol and caffeine. If you are taking bupropion, it is important to be aware of possible interactions with drugs and foods/beverages that could cause unwanted side effects. Continue reading to learn more about bupropion and interactions. 

Key takeaways:

  • Bupropion interacts with various medications, such as other antidepressants, drugs that decrease the seizure threshold, and medicines that increase dopamine levels.
  • Bupropion also interacts with alcohol and caffeine.
  • Bupropion interactions can result in increased side effects and the risk of seizures. 
  • Some drugs should not be taken with bupropion, while others may require a dosage adjustment and close monitoring.
  • Before taking bupropion, tell your healthcare provider about all your medications, including prescription and over-the-counter drugs, vitamins, and supplements. Unless your healthcare provider approves them, do not start any new medications while taking bupropion. 

Bupropion side effects

Before discussing interactions, let’s quickly review the side effects of bupropion. Common side effects include:

  • Headache
  • Dry mouth
  • Stomach problems like nausea, stomach pain, or constipation
  • Appetite and weight loss
  • Agitation 
  • Anxiety 
  • Tinnitus (ringing in the ears)
  • Dizziness 
  • Muscle pain
  • Heart palpitations
  • Trouble sleeping
  • Blurred vision

In some cases, serious side effects may occur, such as seizures or high blood pressure. If you experience symptoms of an allergic reaction, such as hives, difficulty breathing, or swelling of the face, lips, tongue, or throat, get emergency medical help. 

All antidepressants, including bupropion, have a black box warning, which is the strongest warning required by the U.S. Food and Drug Administration (FDA). The warning states that there is an increased risk of suicidal thoughts and behavior in children, adolescents, and young adults who take an antidepressant. People of any age who take bupropion should be closely monitored for suicidal thoughts and behaviors (or changes in mood and behavior).  

Bupropion-drug interactions

Bupropion interacts with various medications, and some effects could be severe. The following section reviews some common interactions. Because the complete list of drug interactions is too long to list every possible drug here, it’s important to consult your healthcare provider to ensure that bupropion is safe for you to take with the medications you currently take, including prescription drugs, over-the-counter (OTC) medicines, vitamins, and supplements.

Monoamine oxidase inhibitors (MAO inhibitors or MAOIs)

Bupropion should never be taken with any drug from the monoamine oxidase inhibitor (MAOI) drug class. The combination could lead to dangerously high blood pressure. In some cases, the combination could also lead to serotonin syndrome, a potentially life-threatening condition due to the buildup of excess serotonin. 

If switching from an MAOI to bupropion, or vice versa, at least two weeks (14 days) must pass between stopping one drug and starting the other. Examples of MAOIs include:

Drugs that affect an enzyme called CYP2B6

Bupropion is metabolized, or broken down, by an enzyme called cytochrome P450 2B6 (CYP2B6). Combining bupropion with another drug that CYP2B6 breaks down can result in a drug interaction.

Some drugs inhibit CYP2B6, which can increase bupropion levels in the body. This may require a lower dosage of bupropion. An example is Plavix (clopidogrel). 

On the other hand, some drugs induce CYP2B6, which means that a slightly higher dose of bupropion may be required, although the maximum dosage should not be exceeded. Examples include:

Drugs that are metabolized by an enzyme called CYP2D6

Bupropion inhibits an enzyme called CYP2D6, which could lead to increased levels in the body of certain medications (examples are listed below), referred to as CYP2D6 substrates. A lower dose of the substrate may be required. Examples include:

Drugs that increase the risk of seizures

Bupropion lowers the seizure threshold, making it more likely that a seizure will occur. Healthcare prescribers never prescribe two formulations of bupropion. For example, you would not take one bupropion product for depression and another for smoking cessation.

The prescribing information recommends using extreme caution when combining bupropion with other medications that lower the seizure threshold, including:

If the combination is prescribed together, the healthcare provider will start with low doses and increase gradually if needed. 

People with a history of seizure disorders should not take bupropion. 

Also, while taking bupropion, you should not abruptly discontinue alcohol, benzodiazepines (anxiety medications such as Xanax), anticonvulsants, or sleep medications such as Ambien (zolpidem). Doing so could increase seizure risk. 

Drugs that increase dopamine levels

Bupropion increases dopamine levels. Other drugs that increase dopamine levels, if combined with bupropion, can cause increased side effects such as agitation, tremors, incoordination, vertigo, and dizziness. If the combination cannot be avoided, healthcare providers will prescribe these medications with caution and closely monitor the patient. Examples include:

Other bupropion interactions

Now, we will discuss other types of bupropion interactions, including alcohol, caffeine, dietary supplements, and certain medical conditions and lab tests.

Bupropion and alcohol 

Alcohol interacts with many prescription drugs, including bupropion. The prescribing information recommends patients minimize or avoid drinking alcohol while taking bupropion. There have been occasional reports of reduced alcohol tolerance and neuropsychiatric events (which could include psychosis, hallucinations, delusions, homicidal or suicidal thoughts, suicide attempts, and others) in people who combined alcohol and bupropion. Also, people who use an excessive amount of alcohol—or stop using alcohol abruptly—while taking bupropion are at increased risk for seizures.

Bupropion and caffeine 

Bad news for coffee lovers—it’s best to avoid caffeine while taking bupropion. The combination could lead to increased side effects, seizures, sleep problems, and worsened anxiety and depression. Because bupropion interacts with caffeine, it’s also best to avoid any supplements containing caffeine, such as green tea extract—and other caffeine-containing products, such as Excedrin products for migraine or Vivarin and other caffeine pills that help you stay awake. 

Bupropion and dietary supplements

In addition to dietary supplements that contain caffeine mentioned above, bupropion interacts with the dietary supplement St. John’s wort. The combination increases the risk of serotonin syndrome. 

Bupropion and certain medical conditions

Bupropion is not safe for everyone. Before taking this medicine, tell your healthcare provider about your medical and family history and any medical conditions you currently have. You should not take bupropion if:

  • You are allergic to bupropion or any ingredient in the medication
  • You currently have, or have a history of, seizures or other conditions that make you more likely to have a seizure, such as an eating disorder like anorexia or bulimia, severe head injury, stroke, brain tumor, or other central nervous system (CNS) conditions
  • You abruptly stop alcohol, antianxiety drugs, barbiturates, or anticonvulsants
  • You have taken an MAOI in the past 14 days
  • You currently use alcohol

Certain other health conditions require a healthcare professional to weigh the benefits and risks of prescribing bupropion, and if prescribed bupropion, the patient will be closely monitored. Some of these conditions include, but are not limited to:

  • Anyone younger than 25 years old
  • Older adults
  • People with a history of substance abuse
  • People with a central nervous system infection
  • People with—or at risk for—bipolar disorder
  • People with kidney or liver problems
  • People with diabetes
  • People with high blood pressure (hypertension)
  • People with angle-closure glaucoma 

People who are pregnant or breastfeeding should always consult their healthcare provider for medical advice.

Bupropion and lab tests

If you need to get a lab test that looks for certain drugs, you will want to know that some people who take bupropion have had false-positive urine tests for amphetamines. This includes prescription drugs like the attention deficit hyperactivity disorder (ADHD) medicine Adderall. Instances may occur even after you stop taking bupropion. Talk to your healthcare provider if this is a concern.

How to minimize bupropion interactions

Here are some suggestions on how to minimize the risk of bupropion interactions:

  • Always make sure your healthcare provider is aware of your current and past medical conditions, family history, allergies to medicines, and all of your medications. Having this information can help your healthcare provider determine if bupropion is safe for you to take. While taking bupropion, consult your healthcare provider or pharmacist before taking any other new medication. 
  • Keep a current list of medications, and show it to your healthcare provider at your appointments. Be sure to include prescription and OTC drugs, vitamins, and dietary supplements. 
  • Before taking bupropion, address questions and concerns with your healthcare provider. Ask what common and serious side effects of bupropion you can expect and what to do if you experience them. Knowing warning signs associated with certain adverse effects can help you know when to get medical help quickly. For example, if you have symptoms of serotonin syndrome, such as agitation, confusion, or stiff muscles, you should get medical help right away. 
  • When you get your prescription, carefully read the Medication Guide and Patient Information Leaflet that comes with your prescription. Consult your healthcare provider if you have any questions or concerns.

When to talk to a healthcare provider about bupropion interactions

Before taking a new medicine, such as bupropion, talk to your healthcare provider to ensure it is safe to take with your current medications. A potential drug interaction may mean that two drugs cannot be taken together—or in some cases, they may be prescribed together at lower doses and with close monitoring.  

This article is not a complete list of bupropion interactions. Communicating openly with your healthcare provider about all medications, supplements, and medical conditions is important to ensure proper management and monitoring.

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