Canadian scholars report that paroxetine application during tamoxifen treatment is associated with an increased risk of death from breast cancer and that paroxetine may attenuate tamoxifen efficacy. A related paper was published in the British Medical Journal (BMJ 2010, 340: c693). The study included 2430 breast cancer patients aged ≥66 years treated with tamoxifen with a selective 5hydroxytryptamine reuptake inhibitor (SSRI). As a result, 15.4% of patients died of breast cancer. After correcting for potential confounding factors, the risk of dying from breast cancer was 24%, 54%, and 91% for those who applied paroxetine for 25%, 50%, and 75% of the tamoxifen course overlap. For every 19.7 patients on the same treatment, 41% of overlapping doses resulted in 1 additional death from breast cancer within 5 years of discontinuation. What drugs should be avoided by those using tamoxifen? In cytochrome P450 tamoxifen (cytochrome P450) is primarily metabolized by the rate-limiting enzyme CYP2D6. This is clinically important because the drug works through active metabolites (midendoxifen) and any factor that interferes with tamoxifen metabolism will result in lower blood levels and reduce the anti-breast cancer effect. Moderate to strong CYP2D6 inhibitors are as follows: * Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) or selective noradrenaline reuptake inhibitors (SNRIs) – paroxetine, fluoxetine, bupropion, and duloxetine * Antipsychotics – methotrexate, fenadine, and pimozide * Cardiac drugs – quinidine and ticlopidine * Infectious disease drugs – Terfenadine and quinidine* Other drugs – cinacalcet treatment usually replaces these items with other alternatives of this class, taking into account the drug with the lowest CYP2D6 inhibitory effect. Alternative drugs with lower in vivo inhibitory activity: *Anti-depressants (SSRIs/SNRIs) – venlafaxine, desvenlafaxine, reboxetine, edipram and mirtazapine *Anti-psychotics – thiothixene, clozapine, risperidone, olanzapine, quetiapine ziprasidone and *Cardiac drugs – diltiazem *Infectious disease drugs – indinavir, saquinavir, nelfinavir and quinidine In addition to avoiding the drugs listed above, many antihistamines (prescription and adult) are moderate inhibitors of CYP2D6, and alternatives with lower inhibitory strength include paracetamol, loratadine cetrizine, and. In addition, among the H2-blockers of histamine are the moderate CYP2D6 inhibitors cimetidine and ranitidine, which have a lower inhibitory strength and should therefore be preferred.