Critical
Paroxetine × Tamoxifen
Selective serotonin reuptake inhibitor (SSRI)×Selective estrogen receptor modulator (SERM)
Mechanism
Tamoxifen is a prodrug activated to endoxifen via CYP2D6. Paroxetine is a strong CYP2D6 inhibitor: endoxifen falls 65%, antiestrogen effect lost. Cohort studies show increased breast cancer mortality with long-term combination.
Symptoms
Tumour progression on imaging after 6-12 months.
Management
Alternative SSRI – sertraline, escitalopram, citalopram, fluvoxamine (no CYP2D6 inhibition). If refractory depression – oncology + psychiatry discussion.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.
Sources
- NCCN: NCCN Guidelines for cancer prevention and risk reduction (2024)– National Comprehensive Cancer Network, 2024
- FDA: Nolvadex (tamoxifen) prescribing information – CYP2D6 metabolism and antidepressant interactions (2018)– FDA Nolvadex label, Clinical Pharmacology §12.3 and Drug Interactions §7
- FDA: Nolvadex (tamoxifen) prescribing information (2018)