The effects of switching antidepressants on endoxifen exposure

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 13

Inclusion Criteria

- Histological or cytological confirmed diagnosis of breast cancer, for which treatment with tamoxifen is indicated (to be evaluated by the treating physician);
- Use of tamoxifen for at least 4 weeks (to guarantee steady-state) and willing to continue the treatment until the end of the study;
- Concomitant use of paroxetine for at least 4 weeks (Amendment: or other antidepressant which has been shown to inhibit CYP2D6 in vitro/in vivo);
- Age > 18 years;
- WHO performance < 1;
- Adequate renal and hepatic functions (see protocol);
- Adequate hematological blood counts (see protocol);
- Written informed consent;
- No chemotherapy within the last 4 weeks before start;
- No radiotherapy within the last 4 weeks before start;
- No concurrent (over the counter) medication or (herbal) supplements, except SSRIs (Amendment: current antidepressant), known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein;
- No concurrent medication or supplements which can interact with venlafaxine and/or escitalopram;
- Abstain from grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea during the study.

Exclusion Criteria

- Pregnant or lactating patients;
- Serious illness or medical unstable condition requiring treatment, symptomatic CNS-metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent;
- Patients with a history of suicide attempts or current suicidal ideation;
- Contra-indications for venlafaxine and/or escitalopram use;
- Patients with Congenital Long QT Syndrome (CLQTS);
- Use of medications or dietary supplements known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein;
- Unwillingness to abstain from grapefruit (juice), (herbal) dietary supplements, herbals, over-the-counter medication (except for paracetamol);
- More than one dose of tamoxifen (20 or 40 mg) per day;
- Non-compliance.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- To determine the effects of switching from the potent CYP2D6 inhibitor<br /><br>paroxetine to a weak CYP2D6 inhibitor (venlafaxine, escitalopram) on the<br /><br>metabolism and plasma pharmacokinetics of tamoxifen and its metabolites in<br /><br>breast cancer patients on tamoxifen therapy.<br /><br><br /><br>Pharmacokinetic parameters to be determined will include clearance (CL), area<br /><br>under the plasma-concentration time curves (AUC), the maximum concentration<br /><br>(Cmax) and time of Cmax (tmax).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- To compare toxic adverse effects in treatment courses with tamoxifen before<br /><br>and after switching from a potent CYP2D6 inhibitor to a weak CYP2D6 inhibitor<br /><br>(changes in adverse effects, severity of adverse effects).<br /><br><br /><br><br /><br><br /><br>Amendment:<br /><br>Tertiary study parameters/outcome:<br /><br>- To study the influence of antidepressants, other than paroxetine, which have<br /><br>been shown to inhibit CYP2D6 in vitro and/or in vivo, on the pharmacokinetics<br /><br>of tamoxifen (patient cases).<br /><br><br /><br>Pharmacokinetic parameters to be determined will include clearance (CL), area<br /><br>under the plasma-concentration time curves (AUC), the maximum concentration<br /><br>(Cmax) and time of Cmax (tmax).</p><br>