Taking Plavix With Wellbutrin

In our latest question and answer, the pharmacist discusses whether or not there is an interaction between Wellbutrin (bupropion) and Plavix (clopidogrel).

Mar 08, 2018

Patricia asked

Can Plavix and Wellbutrin be taken together?


It is sometimes difficult to choose a safe and effective antidepressant medication for individuals who are also taking a blood thinner. Many antidepressant medications work by increasing serotonin levels. However, increased levels of serotonin often have blood thinning effects and can increase the risk of dangerous bleeding events.

Therefore, for some patients, Wellbutrin (bupropion) may be a better choice as it primarily affects the neurotransmitter dopamine and has mild, if any, effect of serotonin.

Unfortunately, Wellbutrin does have an interaction with certain blood thinners, including Plavix (clopidogrel). The interaction between the two is often considered less severe than others but there are cases where your dose of Wellbutrin may need to be adjusted if you take Plavix.

Plavix - Wellbutrin Interaction

Plavix (clopidogrel) is a potent inhibitor of the liver metabolizing enzyme CYP2B6. Wellbutrin is a substrate of CYP2B6, meaning that the enzyme is primarily responsible for metabolizing Wellbutrin and eliminating it from the body.

Theoretically, inhibition of CYP2B6 can lead to increased levels of bupropion in the blood, potentially increasing the risk of side effects such as:

  • Insomnia
  • Headache
  • Tremors
  • Nausea
  • Seizures (rare unless there are pre-existing conditions)

One study that investigated the interaction stated the following:

"[Plavix] clopidogrel 75 mg once daily increased the Cmax [maximum concentration] and AUC [area under the curve] of bupropion by 40% and 60%, respectively. The exposures hydroxybupropion were decreased 50% and 52%, respectively, by clopidogrel"

It is important to note that while bupropion concentrations can be increased when taking in conjunction with Plavix, hydroxybupropion can be decreased.

After taking by mouth bupropion is metabolized in the liver and several active metabolites are formed including:

  • Hydroxybupropion
  • Threohydrobupropion
  • Erythrohydrobupropion

So while inhibition of CYP2B6, as discussed above, will increase levels of bupropion, levels of hydroxybupropion are decreased since less bupropion is being metabolized (i.e. converted to) hydroxybupropion.  

Bupropion and the 3 metabolites listed above are all active in terms of their pharmacologic effects, although bupropion is the most potent. 

The increase in bupropion and decrease in hydroxybupropion via the interaction with Plavix can make it difficult to categorize just how significant the interaction is as one pharmacology active component (bupropion) is being increased while another active competent (hydroxybupropion) is being decreased.

Since bupropion is the most potent and active of the compounds in regard to effect, the net result of the interaction between Wellbutrin in Plavix is generally agreed to be an overall increase in effect. Therefore, there may be a need to decrease the dose of Wellbutrin in some individuals to avoid side effects.

The interaction between Plavix and Wellbutrin must be weighed against the potential interaction between Plavix and other antidepressants that can increase bleeding risk.


  • Plavix (clopidogrel) is an inhibitor of the liver metabolizing enzyme CYP2B6.
  • Wellbutrin (bupropion) is metabolized via CYP2B6.
  • When taking Plavix, bupropion concentrations can be potentially increased while the less active metabolite, hydroxybupropion, may be decreased.
  • Dosage adjustments of Wellbutrin may be needed in certain individuals.

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