A review of medications that could interfere with the effectiveness of tamoxifen by inhibiting CYP2D6 has provided some guidelines on the concurrent use of certain medications. The potential benefit of tamoxifen is related to the status of the metabolizing enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6 is a crucial enzyme in the metabolism of tamoxifen since it is responsible for the generation of endoxifen, which is thought to be responsible for tamoxifen's beneficial activities in breast cancer patients and those at high risk for breast cancer.

Numerous studies have examined the relationship of CYP2D6 status to breast cancer prognosis among women taking tamoxifen - most of the studies have reported that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a higher risk of breast cancer progression. Some common medications taken with tamoxifen can interfere with CYP2D6 function.

After reviewing the published data, the authors have developed a guide for the use of medications that inhibit CYP2D6 in patients using tamoxifen. Medications to avoid include (1) certain antidepressants that act as selective serotonin reuptake inhibitors (SSRIs) or selective noradrenergic reuptake inhibitors (SNRIs) paroxetine, fluoxetine, bupropion, and duloxetine; (2) the antipsychotics thioridazine, perphenazine, and pimozide; (3) the cardiac drugs quinidine and ticlopidine; (4) certain medications for infectious disease, including terbinafine and quinidine; (5) a miscellaneous medication, cinacalcet. There usually are alternatives within each drug class with less CYP2D6 inhibition. The following drugs, which have little or no CYP2D6 inhibition, may be good alternatives: (1) the antidepressants (SSRIs/SNRIs) venlafaxine, desvenlafaxine, reboxetine, escitalopram, and mirtazapine; (2) the antipsychotics thiothixene, clozapine, risperidone, olanzapine, ziprasidone, and quetiapine; (3) the cardiac drug diltiazem; (4) the infectious diseases medications indinavir, saquinavir, nelfinavir, delavirdine, nevirapine, and efavirenz; (5) the miscellaneous medication gabapentin. In addition, many antihistamines (both prescription and over the counter) are intermediate inhibitors of CYP2D6, as is the histamine H2-blockers cimetidine. Alternative medications that have low CYP2D6 inhibition include the antihistamines chlorpheniramine, cetrizine, and loratadine and the histamine H2-blocker ranitidine.