tamoxifen and fluoxetine

Fluoxetine inhibits the cytochrome P450 enzyme CYP2D6, which is responsible for converting tamoxifen to its active metabolite endoxifen. Reduced endoxifen formation may decrease tamoxifen's therapeutic efficacy.

Patients co-prescribed fluoxetine and tamoxifen may have lower plasma levels of endoxifen, potentially leading to an increased risk of breast cancer recurrence. This may result in worse outcomes compared with tamoxifen alone.

Avoid the combination where possible. Consider an alternative antidepressant that does not inhibit CYP2D6, such as venlafaxine or citalopram. If fluoxetine is necessary, monitor clinical response and consider dose adjustment, but this is not generally advised.

Evidence is well established from pharmacokinetic studies and retrospective clinical analyses showing reduced endoxifen levels and increased recurrence risk in patients using CYP2D6 inhibitors.