Certain drugs inhibit the activity of the CYP2D6 enzyme. Patients taking tamoxifen should avoid these drugs, as they reduce the efficacy of tamoxifen and may result in an increased risk of breast cancer recurrence.

Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat hot flashes in women taking tamoxifen and inhibit the activity of CYP2D6 to various degrees. One of the most potent inhibitors of CYP2D6 is paroxetine (Paxil^TM). Patients taking paroxetine who have 2 normal CYP2D6 alleles have concentrations of tamoxifen metabolites similar toPMs whereas patients taking venlafaxine have only mildly reduced CYP2D6 activity. Outcomes data has demonstrated that patients taking SSRIs that are potent CYP2D6 inhibitors have outcomes similar to patients who are PMs.

We recommend that patients taking tamoxifen avoid any potent inhibitors of CYP2D6, including paroxetine, fluoxetine, and sertraline.

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