Disulfiram and Bupropion: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Disulfiram
Bupropion
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased buPROPion exposure and reduced hydroxybuPROPion exposure
Interaction Deep Dive
Coadministration of buPROPion (CYP2B6 substrate) with a CYP2B6 inhibitors is not recommended. It resulted in increased exposure of buPROPion but decreased exposure of hydroxybuPROPion, an active metabolite of buPROPion. Therefore, if buPROPion is used concomitantly with a CYP2B6 inhibitor, dose adjustment of buPROPion may be necessary based on clinical response123. If coadministration of a CYP2B6 inhibitor is required with buPROPion/naltrexone, do not exceed 2 tablets/day of the combination product 4.
Why it happens (mechanism)
Inhibition of CYP2B6-mediated metabolism of buPROPion
Literature reports
3 reports — tap to read
a) Administration of clopidogrel (a CYP2B6 inhibitor) 75 mg once daily with buPROPion increased buPROPion Cmax and AUC by 40% and 60%, respectively, in a trial of healthy male volunteers. Concomitant use of clopidogrel and buPROPion also decreased the Cmax of hydroxybuPROPion by 50% and the AUC by 52% 23.
b) In a drug interaction study of healthy male volunteers, clopidogrel (a CYP2B6 inhibitor) 75 mg once daily or ticlopidine 250 mg twice daily increased exposure of buPROPion by 40 % and 60% for clopidogrel, by 38% and 85% for ticlopidine, respectively. The exposure of buPROPion were decreased 1235 50% and 52%, respectively, by clopidogrel, and 78% and 84%, respectively, by ticlopidine. This effect is thought to be due to the inhibition of the CYP2B6-catalyzed buPROPion hydroxylation 23.
c) In drug interaction study of healthy subjects, prasugrel (a CYP2B6 inhibitor) increased buPROPion Cmax and AUC values by 14% and 18%, respectively, and decreased Cmax and AUC values of hydroxybuPROPion by 32% and 24%, respectively 25.
Common questions
Can I take Disulfiram and Bupropion together?
Increased buPROPion exposure and reduced hydroxybuPROPion exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Disulfiram and Bupropion interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Disulfiram or Bupropion need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (5)
- Product Information: WELLBUTRIN XL(R) oral extended-release tablets, bupropion hydrochloride oral extended-release tablets. Bausch Health US, LLC (per FDA), Bridgewater, NJ, 2024. DailyMed
- Product Information: WELLBUTRIN(R) SR oral sustained-release tablets, bupropion hydrochloride oral sustained-release tablets. GlaxoSmithKline (per FDA), Durham, NC, 2024. DailyMed
- Product Information: WELLBUTRIN(R) oral tablets, bupropion hydrochloride oral tablets. GlaxoSmithKline (per FDA), Durham, NC, 2024. DailyMed
- Product Information: CONTRAVE(R) oral extended-release tablets, naltrexone HCl bupropion HCl oral extended-release tablets. Currax Pharmaceuticals LLC (per FDA), Brentwood, TN, 2024. DailyMed
- Product Information: FORFIVO XL(R) oral extended-release tablets, bupropion hydrochloride oral extended-release tablets. TWi Pharmaceuticals USA, Inc (per FDA), Paramus, NJ, 2024. DailyMed
Keep reading about Disulfiram
Keep reading about Bupropion
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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