Bupropion Interactions: What Drugs Shouldn’t be Used Together

Bupropion Interactions: What Drugs Shouldn’t be Used Together

Bupropion is a medication used to treat depression since 1985 effectively. It inhibits dopamine and norepinephrine reuptake and raises their levels in the body. These two neurotransmitters improve mood and attention, increase alertness, and positively affect adults suffering from depression.

However, bupropion’s therapeutic effect and safety usage depends on its interaction with other medications. Some bupropion interactions, like clopidogrel or carbamazepine, need monitoring and appropriate dose adjustment. On the other hand, concomitant use with antidepressant monoamine oxidase inhibitors (MAOIs) may increase blood pressure; therefore, MAOIs are contraindicated with bupropion. (1)

This article covers potentially serious bupropion interactions. Keep reading to find out which interactions require stopping using the medication.

1. Medications that Affect the CYP2B6 Enzyme

CYP2B6 is an enzyme that is active in bupropion metabolism. Medications that affect the activity of this enzyme impact the bupropion effect. (1)

CYP2B6 belongs to the cytochrome P450 family, representing 6–10% of the total CYP contents in the liver. This enzyme metabolizes bupropion to hydroxybupropion in the liver, a metabolite that is one-half as potent as bupropion. (1-3)

CYP2B6 Inhibitors

Certain medications inhibit the activity of CYP2B6 enzyme, such as:

  • Ticlopidine,
  • Clopidogrel,
  • Sertraline, and
  • Thiotepa. (1)

This inhibition results in an increased amount of bupropion but decreased level of its metabolite, hydroxybupropion. So, the exposure to the active substance and the active metabolite is altered. In this case, when a CYP2B6 inhibitor is used with bupropion, the doctor will adjust the bupropion dose. (1)

CYP2B6 Inducers

On the opposite, another group of medications induces CYP2B6 activity. In this case, the body will be less exposed to bupropion, but the hydroxybupropion level will be higher. When the CYP2B6 inducer is co-administered with bupropion, the doctor may increase the bupropion dose in a range to the maximal recommended daily dose of 450mg. (1)

Ritonavir, lopinavir, and efavirenz are some medications that induce CYP2B6. Carbamazepine, phenobarbital, and phenytoin may induce bupropion metabolism and cause drug interaction. (1)

2. Medications Metabolized by CYP2D6

While the medications described above interact with bupropion by affecting CYP2B6 enzyme activity, bupropion inhibits the CYP2D6 enzyme and impacts the drugs metabolized by this enzyme. (1)

CYP2D6 is another liver enzyme responsible for metabolizing about 20% of the drugs. Bupropion and its metabolites, erythrohydrobupropion, threohydrobupropion, and hydroxybupropion, block the activity of CYP2D6. (4)

Due to this inhibition, the concentration of these medications (substrates) in the body increases, and so do their effects. Therefore, when bupropion is co-administered with CYP2D6 substrates, the doctor will reduce the dose of the concomitant medication. (4)

List of Medications that CYP2D6 Metabolizes

  • Antidepressants – venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline, etc.;
  • Antipsychotics – haloperidol, risperidone, thioridazine, etc.;
  • Beta-blockers – e.g., metoprolol;
  • Type 1C antiarrhythmics – propafenone, flecainide, etc.;
  • Codeine;
  • Tramadol
  • Dextromethorphan; and
  • Duloxetine. (1, 4)

CYP2D6’s other role is activating some medications (e.g., tamoxifen) to be able to show their therapeutic effect. If bupropion inhibits CYP2D6 activity, the co-administered drug will not achieve the required effect. As a result, these medications, when used together with bupropion, need higher doses to achieve the necessary therapeutic effect. (1)

3. Drugs that Lower the Seizure Threshold

Bupropion used alone can cause seizures. If used together with medications that lower the seizure threshold too, the risk of seizure episodes increases.

A sudden, uncontrolled burst of electrical activity may happen in every brain and is called a seizure. Each brain has its own individual potential; people with epilepsy have lower seizure thresholds. Seizures can change behavior, feelings, movements, and consciousness in those experiencing them. (5)

However, some medications may decrease the seizure threshold; bupropion is one of them. The risk of seizure caused by bupropion depends on the dose. The incidence in those taking up to 300mg bupropion hydrochloride extended-release tablets was 1 in 1000 patients. In another study where patients took 300 to 450 mg bupropion HCl immediate-release, 13 out of 3.200 patients experienced seizures. (1)

Using bupropion with other medication that lowers the seizure threshold raises this effect. Due to this, the doctor may prescribe another antidepressant if you use benzodiazepines, barbiturates, and antiepileptic drugs because bupropion is contraindicated. (1)

In other cases of concomitant use, the doctor will recommend bupropion in lower doses and titrate slowly. Tell your doctor if you use any of the following medications:

  • Other bupropion products;
  • Antipsychotics;
  • Tricyclic antidepressants;
  • Theophylline, and
  • Systemic corticosteroids. (1)

They increase the risk if used with bupropion. Because of that, the doctor will initiate a lower dose of bupropion hydrochloride extended-release tablets (XL) and recommend a gradual dose increase. (1)

Be aware that metabolic disorders such as hypoglycemia, hyponatremia (decreased sodium levels), severe liver impairment, use of cocaine, or abuse or misuse of Central Nervous System (CNS) prescription stimulants can also increase the risk of seizures. (1)

4. Levodopa and Amantadine

Bupropion has dopamine agonist effects, meaning that the medication mimics the effects of such substances, and so do levodopa and amantadine. Their concomitant use can result in CNS toxicity. (1)

Levodopa with carbidopa, or amantadine, treats Parkinson’s disease and Parkinson’s-like symptoms.

Dopamine, a feel-good hormone, helps achieve a feeling of pleasure. Aside from improving mood and attention, dopamine plays other roles in the following functions of our body:

  • Sleep;
  • Learning;
  • Movement;
  • Pain processing;
  • Heart rate;
  • Kidney function;
  • Blood vessel function;
  • Lactation. (8)

When bupropion is used with levodopa or amantadine, the cumulative effects of both medications can cause toxic effects. The symptoms that may appear are:

  • Restlessness;
  • Agitation;
  • Repetitive movements on the body (tremors);
  • Impaired coordination (ataxia);
  • Gait disturbance;
  • Vertigo; and
  • Dizziness.

For this reason, your doctor would recommend bupropion to be used with caution. (1)

5. MAO Inhibitors

The concomitant use of bupropion and MAOIs is contraindicated due to the risk of hypertensive reactions. (1)

MAOIs are the first group of antidepressants introduced in practice. Aside from depression, MAOIs treat panic disorder, social phobia, and depression with atypical features. MAOIs block monoamine oxidase, an enzyme active in metabolizing dopamine and other neurotransmitters. Due to this enzyme blockage, dopamine will not break down, and its concentration in the body will increase. (9)

MAOIs increase dopamine, serotonin, norepinephrine, and tyramine levels. Bupropion also increases the dopamine and norepinephrine levels in the body. Dopamine’s other role is to improve heart rate and blood vessel function. (8)

When both medications increase dopamine levels, the blood pressure may increase to a dangerous level. Therefore, it is not recommended to use bupropion if the patient already takes MAOIs. Bupropion may be initiated at least 14 days after discontinuation of MAOIs. (1)

6. Alcohol

Bupropion lowers alcohol body tolerance and may cause adverse neuropsychiatric events. So bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients with abrupt cessation of alcohol. (1)

Alcohol interferes with the brain’s normal functioning, making it harder to think, talk, balance, or judge. When used in combination with bupropion, this effect may be higher because the body cannot tolerate the same amount of alcohol as consumed without bupropion. Therefore, the recommendation is to avoid alcohol consumption or at least minimize it when on bupropion therapy. (1, 10)


Bupropion can safely treat depression as long as you stick to the recommendations. Read the Medication Guide carefully to learn all possible interactions. Tell your doctor the list of all medications you use before using bupropion.

Inform your doctor if you use MAOIs or when you stopped using the therapy, and avoid alcohol consumption.

Be aware of any changes while using bupropion with other medications. Inform your doctor of any adverse reaction you might experience and follow their recommendations.


Is bupropion contraindicated with other medications?

Yes, bupropion is contraindicated with antidepressants MAOIs due to increased dopamine levels in the body. Bupropion is contraindicated in patients using benzodiazepines, barbiturates, and antiepileptic drugs due to the risk of seizures.

Can I use bupropion and clopidogrel together?

Yes, you can use both medications simultaneously. Clopidogrel interacts with bupropion by inhibiting its metabolism. The level of bupropion will increase, while the level of its active metabolite, hydroxybupropion, will decrease. However, your doctor will adjust the bupropion dose when these medications are used together. Therefore, inform your doctor of any medications your are currently taking.

Why did my doctor increase the dose of bupropion while I take carbamazepine?

The antiepileptic carbamazepine induces the activity of the CYP2B6, the enzyme responsible for bupropion metabolism. The effect of this induction is an increased level of the metabolite hydroxybupropion and lower levels of bupropion. Your doctor will increase the bupropion dose to achieve the required effect on your condition.

Can I drink alcohol if I take bupropion?

The recommendation is to avoid alcohol while taking bupropion, or at least minimize its consumption. Talk to your doctor if you consume alcohol regularly.

See Also

Drug Interaction Checker

Bupropion Side Effects

Sertraline Interactions

Sertraline Side Effects

Amlodipine Interactions

Pantoprazole Interactions

Metronidazol Interactions

Meloxicam Interactions

1. Food and Drug Administration, BUPROPION HYDROCHLORIDE – bupropion hydrochloride tablet, extended-release, Lupin Pharmaceuticals, Inc., Apr 2022 https://www.accessdata.fda.gov/spl/data/b94f149e-db1f-4f9f-855a-fc479f94d418/b94f149e-db1f-4f9f-855a-fc479f94d418.xml#section-7

2. S. M. M. Alsanosi, et al., Pharmacokinetic Pharmacogenomics, Handbook of Pharmacogenomics and Stratified Medicine, 2014 https://www.sciencedirect.com/topics/medicine-and-dentistry/cyp2b6

3. M. R. Huecker, A. Smiley, and A. Saadabadi., Bupropion, National Library of Medicine, Apr 2023, https://www.ncbi.nlm.nih.gov/books/NBK470212/

4. Raj Vuppalanchi MD, Metabolism of Drugs and Xenobiotics, Practical Hepatic Pathology, 2011 https://www.sciencedirect.com/topics/medicine-and-dentistry/cyp2d6

5. Epilepsy Foundation, Understanding Seizures, Oct 2019, https://www.epilepsy.com/what-is-epilepsy/understanding-seizures

6. MedlinePlus, Levodopa and Carbidopa, Jan 2022 https://medlineplus.gov/druginfo/meds/a601068.html

7. MedlinePlus, Amantadine, Jun 2021, https://medlineplus.gov/druginfo/meds/a682064.html

8. Harvard Medical School, Dopamine: The pathway to pleasure, Jul 2021, https://www.health.harvard.edu/mind-and-mood/dopamine-the-pathway-to-pleasure

9. T. S. Laban and A. Saadabadi, Monoamine Oxidase Inhibitors (MAOI), National Library of Medicine, Jul 2022, https://www.ncbi.nlm.nih.gov/books/NBK539848/#:~:text=Monoamine%20oxidase%20inhibitors%20(MAOIs)%20are,and%20depression%20with%20atypical%20features

10. National Institute on Alcohol Abuse and Alcoholism, Alcohol and the Brain: An Overview, 2022 https://www.niaaa.nih.gov/publications/alcohol-and-brain-overview

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