Tamoxifen with Phenprocoumon Interaction Details
Brand Names Associated with Tamoxifen
- Nolvadex®
- Soltamox®
- Tamoxifen
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 18, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
Tamoxifen is contraindicated with concomitant coumarin-type anticoagulant therapy in high-risk women and women with ductal carcinoma in situ who use tamoxifen to reduce the incidence of breast cancer. In other clinical situations where concurrent therapy with tamoxifen and warfarin is required, the combination may significantly increase the anticoagulant effect, possibly due to inhibition of CYP2C9-mediated warfarin metabolism by tamoxifen . Although a literature review of 31 patients receiving tamoxifen and warfarin did not reveal a significant increase in risk for bleeding complications, it is recommended to closely monitor INR when tamoxifen is coadministered with warfarin, particularly during tamoxifen initiation and discontinuation .
Severity
Contraindicated
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Coadministration of tamoxifen and coumarin-type anticoagulants, including warfarin, is contraindicated in high-risk women and women with ductal carcinoma in situ where tamoxifen is used to reduce the incidence of breast cancer. In other clinical situations where tamoxifen is used concurrently with warfarin, closely monitor the INR.
Mechanism Of Interaction
Unknown
Literature Reports
A) A review of literature regarding the potential severity and clinical interaction between warfarin and tamoxifen found that the risks of concomitant use do not appear to be any more significant than those associated with other medications. Only primary literature reports for warfarin and tamoxifen interactions were included in the data search. In the 5 publications identified in this review, a total of 31 patients were taking warfarin and tamoxifen concomitantly, with 8 patients experiencing bleeding complications. Confounding factors such as loading regimens, concomitant drugs, diseases, or dietary changes may have contributed to changes in the PT, INR, or bleeding issues. Due to increased levels of anticoagulation and the risk of bleeding complications, concomitant use of warfarin and tamoxifen requires consistent and careful monitoring .
B) A 53-year-old female experienced a high INR following concomitant therapy with tamoxifen and warfarin. Following breast surgery for invasive ductal carcinoma of her left breast, the patient was administered IV chemotherapy with adriamycin followed by prophylactic chemotherapy with tamoxifen citrate (20 mg daily). Five years later, the patient was admitted for adriamycin-induced dilated cardiomyopathy. Patient's hepatic and renal function were normal. ECG revealed dilated left ventricle with global hypokinesia. Based on the patient's continued cardiac deterioration, warfarin 5 mg/daily along with other medications including omeprazole, digoxin, carvedilol, losartan, furosemide/spironolactone, furosemide, metoclopramide, and vitamin B complex were initiated along with her continued regimen of tamoxifen. The patient's INR was carefully monitored; however, on the third day of warfarin initiation, her INR reached 10.27 and warfarin was immediately discontinued. On day 9, warfarin was reinitiated at a lower dose (1 mg) and titrated up to the desired INR on warfarin 2 mg. The patient was stable and discharged on warfarin 2 mg/day. Seven days following discharge, the patient was readmitted for complaints related to her underlying cardiac issues. Her routine INR was 10.87 and a possible drug interaction between warfarin and tamoxifen was established. Warfarin and tamoxifen were both discontinued, however her INR remained high. The patient was given an injection of vitamin K to stabilize her coagulation profile, yet cardiac issues continued to deteriorate and the patient died of her cardiac complications .
C) A study of 13 women (ages 39 to 67 years) with confirmed breast cancer taking tamoxifen 20 mg/daily as part of their adjuvant therapy showed tamoxifen significantly inhibited the CYP2C9 activity within 2 weeks of administration. A single-dose of losartan 25 mg was administered 2 days prior and 2 weeks following the initiation of tamoxifen therapy. Patients were to avoid any other drug that may affect CYP2C9 activity during the study. Losartan and its carboxy metabolite, E3174, urine samples were measured (0 to 8 hour) by high-pressure liquid chromatography. Baseline metabolic losartan to E3174 ratios varied between subjects by approximately 15 fold. The median metabolic ratio prior to tamoxifen treatment was 0.73 (95% confidence interval (CI), 0.15 to 2.3) which increased to 1.66 (95% CI, 0.68 to 5.2; p=0.002) after 2 weeks of tamoxifen treatment. The change in metabolic ratio varied from -11% to 523% (95% CI, 65.3% to 237%). The metabolism of losartan decreased in 10 of the 13 patients .
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.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.