Is Propranolol Safe With Cymbalta And Wellbutrin?

Hello and thank you for reaching out to us!

There is a potential interaction between the three drugs you mentioned in your question, duloxetine, Wellbutrin XL (bupropion extended-release), and propranolol.

However, even though there is an interaction, they can safely be taken together in most individuals if the right precautions are taken.

The Interaction Between Propranolol, Wellbutrin & Duloxetine

The primary interaction between these three drugs is that when all are taken together, the effects of propranolol may be more pronounced (i.e. have a stronger effect than it would if it were taken by itself).

This is because both Wellbutrin (bupropion) and duloxetine (the generic for Cymbalta) inhibit how quickly we metabolize propranolol.

Propranolol Metabolism

Propranolol is metabolized by the CYP2D6 enzyme, one of many enzymes in the cytochrome P450 family of enzymes that are responsible for the metabolism of the vast majority of drugs we ingest.

Wellbutrin and duloxetine are known inhibitors of the CYP2D6 enzyme...they reduce its activity.

Therefore, since the activity of the CYP2D6 enzyme is reduced when these drugs are taken, drugs that are metabolized by it, like propranolol, will be affected.

Propranolol CYP2D6 Interactions

Multiple studies have shown that CYP2D6 inhibitors can increase blood levels of propranolol when taken together.

The prescribing information for propranolol touches on this:

Blood levels and/or toxicity of propranolol may be increased by co-administration with substrates or inhibitors of CYP2D6, such as amiodarone, cimetidine, delavirdine, fluoxetine, paroxetine, quinidine, and ritonavir.

So, if you experience an increase in propranolol blood levels, this means that the effects of the drug could be more pronounced. In other words, you may experience more side effects. The potential side effects include:

• Low blood pressure
• Dizziness
• Reduced heart rate
• Fatigue
• Lightheadedness

How To Approach

Going back to your original question of taking propranolol with Wellbutrin and duloxetine, as mentioned, there is an interaction here, and you could experience the effects of propranolol more strongly.

This doesn't mean you can't take them altogether.

The safest and prudent approach would be to start at the lowest dose of propranolol and see how it affects you.

If you tolerate it well, you could increase the dosage until you find the lowest effective dose.

It's not uncommon for individuals to take drugs that have interactions like this. Doing so can still be safe, just follow the mantra of start low, and go slow.

You mentioned you are starting on a low dose anyway for performance anxiety, so that is a good start. Taking a dose that low, I wouldn't imagine causing too many problems, just be aware of what I've discussed above.

Thank you again for your question!