NCT00667121

Tamoxifen in Women With Breast Cancer and in Women at High-Risk of Breast Cancer Who Are Receiving Venlafaxine, Citalopram, Escitalopram, Gabapentin, or Sertraline

The Effect of Antidepressants and Gabapentin on Tamoxifen Pharmacokinetics: A Prospective Study

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 88 (actual)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Studying samples of blood in the laboratory from patients receiving tamoxifen may help doctors learn more about the effects of other drugs on the level of tamoxifen in the blood. PURPOSE: This clinical trial is studying levels of tamoxifen in the blood of women with breast cancer and in women at high risk of breast cancer who are receiving tamoxifen together with venlafaxine, citalopram, escitalopram, gabapentin, or sertraline.

Detailed description

OBJECTIVES: * To examine the changes in the plasma concentrations of the hydroxylated metabolite, 4-hydroxy tamoxifen, and endoxifen in women with known or at high risk for developing breast cancer who are receiving selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy comprising venlafaxine, citalopram hydrobromide, escitalopram oxalate, gabapentin, or sertraline hydrochloride for the treatment of hot flashes, depression, or any other medically indicated condition. * To evaluate whether genetic variants known to affect the activity of CYP2D6, SULT1A1, and other drug metabolizing enzymes (e.g., UGT's) involved in the biotransformation of tamoxifen citrate affect the plasma concentrations of the hydroxylated metabolites, 4-hydroxy tamoxifen and endoxifen. OUTLINE: This is a multicenter study. Patients receive oral tamoxifen citrate and concurrent selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) therapy comprising oral venlafaxine, citalopram hydrobromide, escitalopram oxalate, sertraline hydrochloride, or gabapentin for 8-24 weeks. Treatment continues in the absence of disease progression. Blood samples are obtained at baseline and after completion of study therapy. Samples are evaluated by pharmacokinetic analysis to determine the effects of SSRI/SNRI study drugs on plasma concentrations of tamoxifen and its metabolites. Plasma levels of tamoxifen citrate, N-desmethyl tamoxifen, 4-OH tamoxifen, and endoxifen are measured using reverse phase high performance liquid chromatography. Blood samples are also analyzed by CYP2D6 genotyping to test for CYP2D6 gene variation (i.e., \*3, \*4, \*6, \*10, \*17, and \*41) in genes that encode tamoxifen-metabolizing enzymes. Additional CYP2D6 alleles, including gene duplication and gene deletion (\*5) are assessed.

Conditions

• Breast Cancer
• Depression
• Hot Flashes
• Psychosocial Effects of Cancer and Its Treatment

Interventions

Type	Name	Description
DRUG	citalopram hydrobromide
DRUG	escitalopram oxalate
DRUG	gabapentin
DRUG	sertraline hydrochloride
DRUG	tamoxifen citrate
DRUG	venlafaxine
GENETIC	molecular genetic technique
OTHER	high performance liquid chromatography
OTHER	laboratory biomarker analysis
OTHER	pharmacological study
PROCEDURE	adjuvant therapy

Timeline

• Start date: 2011-03-16
• Primary completion: 2014-05-12
• Completion: 2014-05-27
• First posted: 2008-04-25
• Last updated: 2025-02-14

Locations

6 sites across 1 country: United States