Tamoxifen Paroxetine Interaction

Selecting antidepressants is so critical.  One of the areas where I believe pharmacists excel above other healthcare professions is the management and recognition of drug interactions.  Here, I breakdown the tamoxifen paroxetine interaction.

A 56 year old female has been having increased depressive symptoms and was placed on paroxetine 20 mg daily.  Her other medications include:

  • Aspirin 81 mg daily
  • Tamoxifen 20 mg daily
  • Lansoprazole 30 mg daily
  • Docusate 100 mg daily
  • Ibuprofen 400 mg as needed
  • Vitamin D 1000 units daily

When reviewing a drug interaction, the first thing I look at is what is going to be the result from this interaction.  In the case of paroxetine interacting with tamoxifen, the end result will potentially be a reduced tamoxifen concentration.  In someone using tamoxifen for breast cancer, this is obviously a significant concern.

Another important question is how does this interaction happen.  Tamoxifen is considered a prodrug.  A prodrug gets converted by the body (through enzymes) to an active form (or more active form).  In this case, that enzyme is CYP2D6.  CYP2D6 is inhibited by paroxetine.  Giving paroxetine to a patient who is taking tamoxifen will therefore block the conversion of tamoxifen to the more active form that provides the benefit to the patient.

With some interactions (particularly many binding interactions), we can alter timing of doses and still keep the patient on the medications that are desired.  Unfortunately in this case, the most appropriate action would be to identify an alternative antidepressant.  You must remember however that many other antidepressants can inhibit 2D6 as well.  Fluoxetine and bupropion are two more examples that can impact CYP2D6.

One of the most challenging aspects of drug interactions is that you can often find conflicting evidence. If you do a literature search on this, you will find reports of this tamoxifen paroxetine interaction having no impact.  However, it is always important to play it on the safe side if other alternatives exist.

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Written By Eric Christianson

February 22, 2017

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