Abiraterone Acetate with Tamoxifen Interaction Details

Brand Names Associated with Abiraterone Acetate

  • Abiraterone
  • Zytiga®

Brand Names Associated with Tamoxifen

  • Nolvadex®
  • Soltamox®
  • Tamoxifen

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Last updated Feb 25, 2024

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Interaction Effect

Increased tamoxifen exposure, increased risk of tamoxifen-related adverse effects or reduced tamoxifen efficacy

Interaction Summary

Abiraterone acetate is a moderate CYP2D6 inhibitor. Coadministration of with CYP2D6 substrates such as tamoxifen increases the concentration of CYP2D6 substrates, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration for which minimal changes in concentration may lead to serious toxicities. If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate[1]. Coadministration of tamoxifen with a potent CYP2D6 inhibitor may inhibit the CYP2D6-mediated metabolism of tamoxifen to its active metabolite, endoxifen [2]. Variations in endoxifen concentrations may result, which may reduce the antitumoral efficacy of tamoxifen and increase the risk of breast cancer relapse [3]. A retrospective analysis revealed a 1.9-fold higher breast cancer recurrence rate in patients receiving a CYP2D6 inhibitor concomitantly with tamoxifen than in those who received tamoxifen alone [4].

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Abiraterone acetate is a moderate CYP2D6 inhibitor. Coadministration of abiraterone with CYP2D6 substrates such as tamoxifen increases the concentration of CYP2D6 substrates, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration for which minimal changes in concentration may lead to serious toxicities. If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug[1]. Monitor patients receiving a CYP2D6 inhibitor concomitantly with tamoxifen closely for loss of tamoxifen efficacy. Coadministration of tamoxifen with a potent CYP2D6 inhibitor may affect tamoxifen efficacy by inhibiting the CYP2D6-mediated metabolism of tamoxifen to its active metabolite, endoxifen [2].

Mechanism Of Interaction

Inhibition of CYP2D6-mediated tamoxifen metabolism by abiraterone acetate

Literature Reports

A) The Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1000 mg daily (plus prednisone). The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3-fold [1].

B) A retrospective analysis of breast cancer patients revealed a 1.9-fold higher 2-year recurrence rate of breast cancer in patients receiving concomitant therapy with tamoxifen and a CYP2D6 inhibitor compared with those receiving tamoxifen therapy alone. Based on medical and pharmacy claims data, 1928 patients who were new to tamoxifen therapy in a 30-month period and who had follow-up data for at least 24 months were included in the analysis. Among these patients, 353 (median age, 53 years) received tamoxifen concurrently with a CYP2D6 inhibitor and 945 (median age, 52 years) received tamoxifen alone. Disease recurrence was identified by diagnosis and insurance billing codes for mastectomy, lumpectomy, lymph node dissection, or radiation therapy, occurring at least 6 months after initiation of tamoxifen therapy. The 2-year breast cancer recurrence rate was 13.9% in women receiving concomitant tamoxifen and CYP2D6 inhibitor therapy compared with 7.5% in women receiving tamoxifen alone (95% CI, 1.33 to 2.76, p=0.001; hazard ratio, 1.92). Intervention procedures in the tamoxifen/CYP2D6 inhibitor group to treat breast cancer included mastectomy (54%), lumpectomy (36%), and radiation therapy (47%); corresponding intervention rates in the tamoxifen only group were 52%, 38%, and 46%, respectively [4].

C) The use of CYP2D6 inhibitors should be avoided in breast cancer patients receiving tamoxifen due to the risk of substantially reduced plasma concentrations of the antiestrogenic tamoxifen metabolite, endoxifen. In a prospective randomized trial, 256 postmenopausal breast cancer patients receiving tamoxifen were genotyped and grouped according to CYP2D6 metabolism and medication history. Adjusted analysis showed that decreased metabolizers (n=65) had significantly worse relapse-free survival (hazard ratio 1.74; 95% confidence interval (CI), 1.1 to 2.74; p=0.017), disease-free survival (hazard ratio 1.6; 95% CI, 1.06 to 2.43; p=0.027), and shorter time to recurrence (hazard ratio 1.91; 95% CI, 1.05 to 3.45; p=0.034) compared with extensive metabolizers (n=115). The greatest risk of breast cancer relapse was found in the poor metabolizer group (hazard ratio 3.12; 95% CI, 1.37 to 7.55; p=0.007) [3]. Decreased metabolizers had either one or two CYP2D6*4 alleles or was receiving a CYP2D6 inhibitor together with tamoxifen (regardless of genotype), and extensive metabolizers did not have a *4 allele and were not receiving a CYP2D6 inhibitor [5].

References

    1 ) Product Information: AKEEGA(TM) oral tablets, niraparib, abiraterone acetate oral tablets. Janssen Biotech, Inc. (per FDA), Horsham, PA, 2023.

    2 ) Johnson MD, Zuo H, Lee KH, et al: Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 2004; 85(2):151-159.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

    3 ) Goetz MP, Knox SK, Suman VJ, et al: The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 2007; 101(1):113-121.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

    4 ) Aubert RE; Stanek EJ; and Yao J: Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors. American Society of Clinical Oncology. Alexandria, VA. 2009. Available from URL: http://www.asco.o... . As accessed 2009-06-22.

    5 ) Goetz MP, Kamal A, & Ames MM: Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response. Clin Pharmacol Ther 2008; 83(1):160-166.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

Abiraterone Acetate Overview

  • Abiraterone is used in combination with prednisone to treat a certain type of prostate cancer that has spread to other parts of the body. Abiraterone is in a class of medications called androgen biosynthesis inhibitors. It works by decreasing the amount of certain hormones in the body.

See More information Regarding Abiraterone

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.

See More information Regarding Tamoxifen

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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.