Should CYP2D6 inhibitors be administered in conjunction with tamoxifen?

2011 ◽  
Vol 11 (2) ◽  
pp. 185-193 ◽  
Author(s):  
Hitoshi Zembutsu ◽  
Mitsunori Sasa ◽  
Kazuma Kiyotani ◽  
Taisei Mushiroda ◽  
Yusuke Nakamura
Keyword(s):  
Cyp2d6 Inhibitors

Avoidance of CYP2D6 Inhibitors in Patients Receiving Tamoxifen

2010 ◽  
Vol 28 (29) ◽  
pp. e584-e585 ◽  
Author(s):  
Roberta Ferraldeschi ◽  
Sacha J. Howell ◽  
Alastair M. Thompson ◽  
William G. Newman
Keyword(s):  
Cyp2d6 Inhibitors

Effect of Concomitant CYP2D6 Inhibitor Use and Tamoxifen Adherence on Breast Cancer Recurrence in Early-Stage Breast Cancer

2010 ◽  
Vol 28 (14) ◽  
pp. 2423-2429 ◽  
Author(s):  
Vincent O. Dezentjé ◽  
Nico J.C. van Blijderveen ◽  
Hans Gelderblom ◽  
Hein Putter ◽  
Myrthe P.P. van Herk-Sukel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Early Stage ◽  
Cancer Recurrence ◽  
Cox Proportional Hazards Model ◽  
Breast Cancer Recurrence ◽  
Tamoxifen Treatment ◽  
Adjuvant Tamoxifen ◽  
Increased Risk ◽  
Cyp2d6 Inhibitors

Purpose The use of cytochrome P450 2D6–inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in patients with breast cancer. The objectives of this study were to relate concomitant CYP2D6 inhibitor use and tamoxifen adherence to breast cancer event-free time (EFT). Patients and Methods Data were from PHARMO and included a community pharmacy dispensing database; PALGA, a nationwide pathology database; and the Dutch Medical Register in the Netherlands. Patients with breast cancer treated with adjuvant tamoxifen between 1994 and 2006 were included. A Cox proportional hazards model with a time-dependent definition for concomitant CYP2D6 inhibitor exposure was used. Adherence calculated over the first year after tamoxifen initiation was related to breast cancer events in the following period. Results In total, 1,962 patients with breast cancer using tamoxifen were included, among whom 150 (7.6%) frequently used a CYP2D6 inhibitor during tamoxifen treatment. No association between concomitant CYP2D6 inhibitor use and breast cancer recurrence was observed (adjusted hazard ratio [HR], 0.87; 95% CI, 0.42 to 1.79; P = .69). Poor tamoxifen adherence was associated with lower EFT (adjusted HR, 0.987; 95% CI, 0.975 to 0.999; P = .029). Conclusion This observational study did not show an association between concomitant CYP2D6 inhibitor use and breast cancer recurrence among patients treated with adjuvant tamoxifen despite the strong biologic rationale. This study shows, to the best of our knowledge for the first time, that poor tamoxifen adherence is associated with an increased risk of breast cancer events.

Pharmacogenomics of Tamoxifen Therapy

2009 ◽  
Vol 55 (10) ◽  
pp. 1770-1782 ◽  
Author(s):  
Hiltrud Brauch ◽  
Thomas E Mürdter ◽  
Michel Eichelbaum ◽  
Matthias Schwab
Keyword(s):  
Cytochrome P450 ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Plasma Concentrations ◽  
Hot Flashes ◽  
Parent Drug ◽  
Endocrine Treatment ◽  
Active Metabolites ◽  
Recurrence Rates ◽  
Hormone Receptor Positive ◽  
Cyp2d6 Inhibitors

Abstract Background: Tamoxifen is a standard endocrine therapy for the prevention and treatment of steroid hormone receptor–positive breast cancer. Content: Tamoxifen requires enzymatic activation by cytochrome P450 (CYP) enzymes for the formation of active metabolites 4-hydroxytamoxifen and endoxifen. As compared with the parent drug, both metabolites have an approximately 100-fold greater affinity for the estrogen receptor and the ability to inhibit cell proliferation. The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. In particular, nonfunctional (poor metabolizer) and severely impaired (intermediate metabolizer) CYP2D6 alleles are associated with higher recurrence rates. Summary: Accordingly, CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) genotyping before treatment to predict metabolizer status may open new avenues for individualizing endocrine treatment, with the maximum benefit being expected for extensive metabolizers. Moreover, strong CYP2D6 inhibitors such as the selective serotonin reuptake inhibitors paroxetine and fluoxetine, which are used to treat hot flashes, should be avoided because they severely impair formation of the active metabolites.

The effect of CYP 2D6 genotype and CYP2D6 inhibitors on tamoxife

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 508-508
Author(s):  
V. Stearns ◽  
D. F. Hayes ◽  
Y. Jin ◽  
L. Ullmer ◽  
A. Nguyen ◽  
...  
Keyword(s):  
Cyp2d6 Inhibitors ◽  
Cyp 2D6

CYP2D6*4 polymorphism as blood predictive biomarker of breast cancer relapse in patients receiving adjuvant tamoxifen

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 590-590 ◽  
Author(s):  
S. Gonzalez-Santiago ◽  
R. Zárate ◽  
J. Haba-Rodríguez ◽  
A. Gómez ◽  
E. Bandrés ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Univariate Analysis ◽  
Disease Recurrence ◽  
Adjuvant Tamoxifen ◽  
Cyp2d6 Genotype ◽  
Disease Relapse ◽  
Breast Cancer Patients ◽  
Cyp2d6 Inhibitors

590 Background: Polymorphisms in cytochrome P450 2D6 gene affect the plasma concentration of tamoxifen active metabolites (endoxifen). Some drugs are known to be CYP2D6 inhibitors. We aim to determine the relationship between CYP2D6*4 polymorphisms, concomitant CYP2D6 inhibitors use and clinical outcomes of breast cancer patients receiving adjuvant tamoxifen (TAM). Patients and Methods: CYP2D6*4 (1934 G>A+1) genotype was determinated from DNA of blood samples using PCR-RFLP technique and Taqman Allelic Discrimination Assay in a series of 84 breast cancer patients receiving adjuvant TAM. CYP2D6 inhibitors were recorded. Chi-square test and logistic regression models were used to determinate association between genotype, use of concomitant CYP2D6 inhibitors and disease relapse rate. Results: In our 84 patients series mean age was 51.5y. (33–71). 14.8% were stage I, 58.0% stage II and 27.2% stage III. 61.4% were nodes positive and 98.7% tumors had positive hormonal receptors. We observed disease recurrence in 36.9% of cases. The mean following-up was 5.5 y. Genotype frequency was: wt/wt (57.1%), wt/*4 (40.5%) and *4/*4 (2.4%). 50% (18 of 36) of patients with the wt/*4 + *4/*4 genotypes had disease relapse compared with 27% (13 of 48) with wt/wt genotype (P= 0.041). Only 6 patients received concomitants CYP2D6 inhibitors, mainly antidepressants, all of them with the wt/*4 genotype. 50% presented disease relapse. Clinical pathological variables were evaluated and significant relation was found between stage and disease relapse by univariate analysis (P= 0.001). We investigated whether CYP2D6*4 genotype and stage to diagnosis could influence in disease relapse. For these analyses we use as reference group the genotype wt/wt. We observed that combined genotype wt/*4 + *4/*4 was more strongly associated with disease recurrence than wt/wt genotype (adjusted hazard ratio [HR], 2.82, 95% confidence interval [CI] 1.0- 7.9) P= 0.049. Conclusions: Breast cancer patients with the CYP2D6 *4/*4 or wt/*4 genotype could have lower benefit of TAM adjuvant treatment and tend to have a higher risk of disease relapse. Pre-treatment CYP2D6 genotype determination from blood sample could predicts TAM clinical outcomes and help to oncologist in treatment decision. No significant financial relationships to disclose.

Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors

2009 ◽  
Vol 27 (18S) ◽  
pp. CRA508-CRA508 ◽  
Author(s):  
R. E. Aubert ◽  
E. J. Stanek ◽  
J. Yao ◽  
J. R. Teagarden ◽  
M. Subar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Cyp2d6 Inhibitors

scholarly journals Prevalence of the co-prescription of tamoxifen and CYP2D6 inhibitors in Saudi population: A cross sectional study

2020 ◽  
Vol 28 (4) ◽  
pp. 440-444
Author(s):  
Azher Arafah ◽  
Khalid Yakout ◽  
Muneeb U. Rehman ◽  
Ammar Mohammed Alsharif ◽  
Mohammad H. AlJawadi ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Saudi Population ◽  
Sectional Study ◽  
Cross Sectional ◽  
Cyp2d6 Inhibitors

scholarly journals How are Pain Treatment Response Rates In Primary Care Influenced By Co-Prescription of Cyp2d6 Inhibitors?

2015 ◽  
Vol 18 (7) ◽  
pp. A659
Author(s):  
RD Pockett ◽  
CJ O’Leary ◽  
P Anderson ◽  
A Nasser ◽  
TG Winfield ◽  
...  
Keyword(s):  
Primary Care ◽  
Treatment Response ◽  
Pain Treatment ◽  
Response Rates ◽  
Cyp2d6 Inhibitors

Paroxetine Markedly Increases Plasma Concentrations of Ophthalmic Timolol; CYP2D6 Inhibitors May Increase the Risk of Cardiovascular Adverse Effects of 0.5% Timolol Eye Drops

2014 ◽  
Vol 42 (12) ◽  
pp. 2068-2076 ◽  
Author(s):  
Jukka Mäenpää ◽  
Marjo Volotinen-Maja ◽  
Hannu Kautiainen ◽  
Mikko Neuvonen ◽  
Mikko Niemi ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Plasma Concentrations ◽  
Eye Drops ◽  
Cyp2d6 Inhibitors
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