ReviewEuropean journal of drug metabolism and pharmacokinetics2018
The Underrated Risks of Tamoxifen Drug Interactions.
Review in European journal of drug metabolism and pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Concurrent Antidepressant Use and Metastasis Risk Among Women Receiving Tamoxifen for Breast Cancer: A Real-World Cohort Study.Psycho-oncology · 2026Article
- Assessing Practice Patterns of Antidepressant Medication and Tamoxifen Use Among Patients With Hormone Receptor-Positive Breast Cancer.Cancer reports (Hoboken, N.J.) · 2026Article
- Drug-Drug Interactions in Recently Approved Antibacterials: A Mini Review.European journal of drug metabolism and pharmacokinetics · 2026Review
- Article
- Drug Interactions With Tamoxifen and Treatment Effectiveness in Premenopausal Breast Cancer Patients: A Bayesian Joint Modeling Approach.Pharmacoepidemiology and drug safety · 2025Article
- Antidepressant Use Trajectories and Risk of Discontinuation After Adolescents and Young Adult Cancer Diagnosis.Pharmacoepidemiology and drug safety · 2025Article
- Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini review.Frontiers in pharmacology · 2025Review
- Formation of potentially toxic metabolites of drugs in reactions catalyzed by human drug-metabolizing enzymes.Archives of toxicology · 2024Review
- Structure-Activity Relationships of Triphenylethylene Derivatives and Their Evaluation as Anticancer and Antiviral Agents.ACS omega · 2023Article
- Effects of Genetic Polymorphisms of Drug Metabolizing Enzymes and co-Medications on Tamoxifen Metabolism in Black South African Women with Breast Cancer.Clinical pharmacology and therapeutics · 2023Article
- Adherence to endocrine therapy in early breast cancer in relation to Cytochrome P450 2D6 genotype: a comparison between pharmacy dispensation data and medical records.Breast cancer research and treatment · 2023Article
- Pharmacokinetics of Tamoxifen and Its Major Metabolites and the Effect of the African Ancestry Specific CYP2D6*17 Variant on the Formation of the Active Metabolite, Endoxifen.Journal of personalized medicine · 2023Article
- Review
- Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.Pharmacogenomics and personalized medicine · 2022Review
- Hydroethanolic Extract of DefattedMedicines (Basel, Switzerland) · 2021Article
- Article
- Cytochrome P450 expression, induction and activity in human induced pluripotent stem cell-derived intestinal organoids and comparison with primary human intestinal epithelial cells and Caco-2 cells.Archives of toxicology · 2021Article
- Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.Archives of toxicology · 2021Review
- Nationwide prevalence of potential drug-drug interactions associated with non-anticancer agents in patients on oral anticancer agents in South Korea.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2020Article
- Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen.Journal of cancer research and clinical oncology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tamoxifen is a prodrug, and most of the therapeutic effect in treating breast cancer stems from its metabolite, endoxifen. Since cytochrome P450 (CYP) 2D6 is the most important enzyme in the production of endoxifen, drugs that inhibit CYP2D6 would be expected to reduce tamoxifen efficacy. In addition to drug-drug interactions (DDI) involving CYP2D6, there is growing evidence that enzyme inducers can substantially alter the disposition of endoxifen, reducing tamoxifen efficacy. Although the clinical evidence on the impact of CYP2D6 inhibitors on tamoxifen efficacy is mixed, there were serious flaws in many of the studies. Thus, there is a reasonable chance that CYP2D6 inhibitors do in fact inhibit tamoxifen efficacy. Tamoxifen has extraordinarily complex pharmacokinetics, with more than a dozen drug-metabolizing enzymes and transporters involved in its disposition. Enzyme inducers may increase the activity of several of these pathways, including phase II enzymes, ABC transporters, and various CYP enzymes other than CYP2D6. Based on current clinical evidence, one could argue that enzyme inducers are potentially more dangerous than CYP2D6 inhibitors in patients taking tamoxifen. Moreover, early evidence suggests that the combination of CYP2D6 inhibitors plus enzyme inducers may produce catastrophic inhibition of tamoxifen efficacy. One could argue that, given the available evidence, an agnostic "wait and see" position on tamoxifen DDI is ethically untenable, and that many women with breast cancer are currently being subjected to an unnecessary risk of cancer recurrence. Specific recommendations to reduce the risk of adverse tamoxifen DDI are offered for consideration.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.