Tamoxifen with Fluoxetine Interaction Details

Brand Names Associated with Tamoxifen

Brand Names Associated with Fluoxetine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 18, 2023

Interaction Effect

Decreased plasma concentration of the active metabolite of tamoxifen; increased risk of QT-interval prolongation

Interaction Summary

Large retrospective studies have found no significant impact of antidepressants, including fluoxetine, on the risk of subsequent breast cancer nor an increased risk of death from breast cancer with concomitant use of tamoxifen and fluoxetine, despite an increased risk found with paroxetine . When concomitant antidepressant therapy is necessary, alternatives with little or no CYP2D6 inhibition should still be considered . Additionally, concomitant administration of fluoxetine and tamoxifen may result in additive effects on the QT interval and should be avoided. Consider periodic ECG monitoring in patients with risk factors for QT prolongation and ventricular arrhythmia .

Severity

Major

Onset

Delayed

Evidence

Theoretical

How To Manage Interaction

While coadministration of paroxetine, another SSRI with CYP2D6 inhibiting properties, and tamoxifen may decrease the plasma concentration of the major active metabolite of tamoxifen and may reduce the clinical benefit of tamoxifen , data have not supported a significant effect of fluoxetine on breast cancer events with tamoxifen . However, when concomitant antidepressant therapy is necessary, consider alternatives with little or no CYP2D6 inhibition . Additionally, concomitant administration of fluoxetine and tamoxifen may result in additive effects on the QT interval and should be avoided. Consider periodic ECG monitoring in patients with risk factors for QT prolongation and ventricular arrhythmia .

Mechanism Of Interaction

Inhibition of CYP2D6-mediated tamoxifen metabolism; additive QT-interval prolongation effects

Literature Reports

A) The risk of subsequent breast cancer was not significantly increased with concurrent use of antidepressants in a retrospective review of 16,887 insured women receiving tamoxifen for at least 6 months following a diagnosis of Stage 0 to II breast cancer. The median duration of tamoxifen use was 2.7 years. Of the 8089 patients who were prescribed antidepressants, the median days of overlap between antidepressant and tamoxifen use was 144 days. After a median follow-up of 6 years, 17.4% of all patients developed a subsequent breast cancer. Of the 10.6% of patients who received paroxetine, 25%, 50%, and 75% increases in overlapping use during the first year of tamoxifen were associated with the highest increases in the risk of subsequent breast cancer (6%, 13%, and 20%, respectively), but these increases were not significant and diminished over time. Fluoxetine was the most common antidepressant prescribed (19.9%) and was associated with a 0%, 1%, and 3% nonsignificant increase in the risk of subsequent breast cancer for the corresponding 25%, 50%, and 75% increases in overlapping use during the first year of tamoxifen. Other agents tested were grouped into categories of other SSRIs, tricyclics, and other types that included venlafaxine, trazodone, bupropion, and tetracyclics .

B) Results from a retrospective study demonstrated that concomitant use of paroxetine and tamoxifen is associated with an increased risk of death from breast cancer that is directly related to the duration of concomitant therapy, while the risk is not increased with other SSRIs, including fluoxetine. Participants in the study included females at least 66 years old who were newly treated with tamoxifen for breast cancer and who also received a single SSRI antidepressant. Of the 2430 participants, 2025 initiated tamoxifen within 1 year of being diagnosed with breast cancer and the median duration of tamoxifen therapy was 4 years. Paroxetine was the most common SSRI prescribed (n=630) while others consisted of sertraline (n=541), citalopram (n=467), venlafaxine (n=365), fluoxetine (n=253), and fluvoxamine (n=174). After a mean follow-up of 2.38 years, 374 women died of breast cancer. Absolute increases of 25%, 50%, and 75% in the proportion of time on tamoxifen concomitantly with paroxetine were associated with significant increases of 24%, 54%, and 91% in the risk of death from breast cancer, respectively. No other SSRI was associated with an increased risk of breast cancer mortality when administered during tamoxifen therapy .

Tamoxifen Overview

• Tamoxifen is used to treat breast cancer that has spread to other parts of the body in men and women. It is used to treat early breast cancer in women who have already been treated with surgery, radiation, and/or chemotherapy. It is used to reduce the risk of developing a more serious type of breast cancer in women who have had ductal carcinoma in situ (DCIS; a type of breast cancer that does not spread outside of the milk duct where it forms) and who have been treated with surgery and radiation. It is used to reduce the risk of breast cancer in women who are at high risk for the disease due to their age, personal medical history, and family medical history.

• Tamoxifen is in a class of medications known as antiestrogens. It blocks the activity of estrogen (a female hormone) in the breast. This may stop the growth of some breast tumors that need estrogen to grow.

Fluoxetine Overview

• Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.