Stay Up to Date
Breaking News,
Updates, & More
Click Here to
Subscribe

Venlafaxine Lowers Endoxifen Levels, May Affect Tamoxifen Effectiveness

TOP - February 2013 VOL 6, NO 1 published on March 4, 2013 in Breast Cancer

The antidepressant venlafaxine is often prescribed to patients with breast cancer who are taking tamoxifen, to help reduce the side effect of hot flashes. But according to research presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, venlafaxine may reduce the effectiveness of the drug.

The findings came from a multicenter prospective pharmacologic study that analyzed paired blood samples from 30 women taking venlafaxine for at least 4 weeks for the treatment of hot flashes. Blood was taken before starting venlafaxine and 8 to 16 weeks afterward. Genotyping was conducted for alleles associated with no, reduced, and ultrarapid metabolism. The aim was to examine whether venlafaxine altered the pharmacokinetics of tamoxifen and to determine the distribution of CYP2D6 genotypes in this population.

CYP2D6 is the rate-limiting enzyme responsible for the metabolic activation of tamoxifen to endoxifen. Among women taking tamoxifen, those who are extensive metabolizers of CYP2D6 have higher endoxifen concentrations, have more vasomotor symptoms, and are more likely to discontinue treatment, compared with poor metabolizers.

“The data regarding CYP2D6 genotype and cancer recurrence [have] been mixed,” said lead investigator Matthew Goetz, MD, of the Mayo Clinic in Rochester, Minnesota. “Venlafaxine is a weak CYP2D6 inhibitor not known to alter tamoxifen pharmacokinetics and is commonly recommended for tamoxifen-induced hot flashes.”

Women with tamoxifen-induced vasomotor symptoms requiring ameliorative treatment with venlafaxine were predominantly CYP2D6 extensive and ultrarapid metabolizers. Venlafaxine significantly decreased endoxifen concentrations. Across all genetic subgroups, levels were depressed by a median of about 1.6 ng/mL over time (P = .04). Limited evidence suggests that at least 6 ng/mL is needed for the prevention of breast cancer events; in the present study, 3 women with low CYP2D6 activity had levels drop below that.

Goetz acknowledged that the optimal endoxifen concentration needed for benefit is still unknown, as is the effect of venlafaxine on breast cancer outcomes. “The bottom line is that there is a decrease [in concentration]. It’s small but it’s statistically significant. The question really is, ‘Are there subgroups of patients in which this is important?’”

He concluded that “given prior data linking low endoxifen concentrations with recurrence, venlafaxine should be used with caution in tamoxifen-treated patients.”

Session moderator Hiltrud Brauch, PhD, of the Margarete Fischer-Bosch Institute of Clini-cal Pharmacology in Stuttgart, Germany, led a 2009 study showing that variations in CYP2D6 metabolism have an effect on disease-free and event-free survival in patients taking tamoxifen. “Poor metabolizers do not benefit from tamoxifen as well as extensive metabolizers,” she said. “The long and the short of it is that this matters to women.” l

Reference
Goetz MP, Suman V, Henry NL, et al. Venlafaxine inhibits the CYP2D6 mediated metabolic activation of tamoxifen: results of a prospective multicenter study: (NCT00667121). Presented at: 2012 CTRC-AACR San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX. Abstract PD10-08.

Related Items
Adding Ribociclib to Endocrine Therapy May Reduce Risk for Recurrence in HR-Positive, HER2-Negative, Early Breast Cancer
Patricia Stewart
TOP - July 2023 Vol 16, No 4 – Online Only published on July 17, 2023 in ASCO 2023 Highlights, Breast Cancer
FDA Updates Mammography Regulations in MQSA Final Rule
TOP - May 2023 Vol 16, No 3 published on May 15, 2023 in Breast Cancer, Healthcare Policy
Pausing Endocrine Therapy to Become Pregnant Appears Safe for Women with Breast Cancer
Patricia Stewart
TOP - March 2023 Vol 16, No 2 published on March 14, 2023 in Breast Cancer, SABCS
Factors Associated with Greater Risk for Abemaciclib Discontinuation in Patients with Early-Stage Breast Cancer
William King
TOP - November 2022 Vol 15, No 6 published on November 9, 2022 in Breast Cancer
Radiation Therapy May Be Omitted for Some Older Women with Luminal A Breast Cancer
Patricia Stewart
TOP - November 2022 Vol 15, No 6 published on November 9, 2022 in Breast Cancer
Trastuzumab Deruxtecan Represents New Standard of Care for Patients with HER2-Low Metastatic Breast Cancer
William King
TOP - September 2022 Vol 15, No 5 published on September 15, 2022 in Breast Cancer
Pembrolizumab plus Chemotherapy Prolongs Survival in Patients with Triple-Negative Breast Cancer and PD-L1 Combined Positive Score ≥10
Patricia Stewart
TOP - March 2022 Vol 15, No 2 published on March 16, 2022 in SABCS, Breast Cancer
Trastuzumab Deruxtecan Beats Trastuzumab Emtansine as Second-Line Therapy for HER2-Positive Metastatic Breast Cancer
TOP - March 2022 Vol 15, No 2 published on March 16, 2022 in SABCS, Breast Cancer
Olaparib Extends Disease-Free Survival in Patients with Early-Stage Breast Cancer and BRCA Mutation
William King
TOP - November 2021 Vol 14, No 7 published on November 10, 2021 in Breast Cancer
Tucatinib plus Trastuzumab and Capecitabine Triplet Maintains Survival Benefit in HER2-Positive Metastatic Breast Cancer: Updated Results from HER2CLIMB Trial
Charlie Dawson
TOP - September 2021 Vol 14, No 5 published on September 7, 2021 in Breast Cancer
Last modified: July 11, 2023