A 49-year-old woman on adjuvant tamoxifen for breast cancer has disabling hot flushes unresponsive to lifestyle measures. A clinician considers a selective serotonin reuptake inhibitor. Which agent must be avoided in this patient?
- A Paroxetine ✓
- B Venlafaxine
- C Desvenlafaxine
- D Gabapentin
Correct answer: A. Paroxetine
Explanation
Tamoxifen is a prodrug converted to its active metabolite endoxifen mainly by hepatic CYP2D6. Paroxetine and fluoxetine are potent CYP2D6 inhibitors and reduce endoxifen levels, potentially undermining the anti-oestrogen effect, so they are avoided during tamoxifen therapy. Venlafaxine and desvenlafaxine are SNRIs with minimal CYP2D6 inhibition and are established nonhormonal options for flushing, while gabapentin acts through a different pathway altogether and carries no such interaction.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.