Sertraline with Tamoxifen Interaction Details
Brand Names Associated with Sertraline
- Sertraline
- Zoloft®
Brand Names Associated with Tamoxifen
- Nolvadex®
- Soltamox®
- Tamoxifen
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 18, 2023
Interaction Effect
Reduced exposure of active tamoxifen metabolites and an increased risk of QT interval prolongation
Interaction Summary
Avoid coadministration of sertraline and tamoxifen as this may increase the risk of QT prolongation and/or ventricular arrhythmias. Coadministration of sertraline and tamoxifen may decrease the plasma concentration of the major active metabolite of tamoxifen ; however, large retrospective studies have found no significant impact of antidepressants, including sertraline, on the risk of subsequent breast cancer nor an increased risk of death from breast cancer with concomitant use of tamoxifen and sertraline, despite an increased risk found with PARoxetine. When concomitant antidepressant therapy is necessary, alternatives with little or no CYP2D6 inhibition should be considered .
Severity
Major
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
Avoid coadministration of sertraline and tamoxifen as this may increase the risk of QT prolongation and/or ventricular arrhythmias. Additionally, coadministration of tamoxifen and CYP2D6 inhibitors, such as sertraline, may decrease exposure to the active tamoxifen metabolite ; however, data have not supported a significant effect of sertraline on breast cancer events with tamoxifen despite conflicting clinical results with PARoxetine . When concomitant antidepressant therapy is necessary, consider alternatives with little or no CYP2D6 inhibition .
Mechanism Of Interaction
Inhibition of CYP2D6-mediated tamoxifen metabolism by sertraline; additive QT interval prolongation
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 sertraline. 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 .
C) Concomitant use of PARoxetine, a potent inhibitor of CYP2D6, and tamoxifen, which requires activation by CYP2D6 enzymes to the antiestrogenic metabolite (endoxifen), results in substantially reduced plasma concentrations of endoxifen. Eighty newly diagnosed breast cancer patients taking tamoxifen 20 mg/day were genotyped for the common alleles of the CYP2D6, CYP2C9, CYP3A5, and sulfotransferase (SULT) 1A1 genes. After 1 and 4 months of tamoxifen treatment, plasma concentrations of tamoxifen and endoxifen were measured. After 4 months of tamoxifen, plasma endoxifen concentrations were significantly lower in those with a CYP2D6 homozygous variant genotype (20 nM) or a heterozygous genotype (43.1 nM) than those with a homozygous wild-type genotype (78 nM). The mean plasma endoxifen concentration for subjects with a homozygous wild-type genotype who were taking CYP2D6 inhibitors was 58% lower than those not taking such inhibitors (38.6 nM vs 91.4 nM). Concomitant use of venlafaxine, a weak inhibitor of CYP2D6, resulted in slightly reduced plasma concentrations of endoxifen, while the use of PARoxetine, a potent inhibitor of CYP2D6, resulted in substantial reductions in endoxifen concentrations, and sertraline resulted in intermediate reductions in endoxifen levels between those of venlafaxine and PARoxetine .
Sertraline Overview
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Sertraline 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), panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks), posttraumatic stress disorder (disturbing psychological symptoms that develop after a frightening experience), and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). It is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. Sertraline is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amounts of serotonin, a natural substance in the brain that helps maintain mental balance.
Tamoxifen Overview
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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.
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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.
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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:
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.