Warfarin with Etoposide Interaction Details

Brand Names Associated with Warfarin

Brand Names Associated with Etoposide

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 07, 2023

Interaction Effect

Increased risk for elevated INR and subsequent bleeding

Interaction Summary

Concomitant use of etoposide and warfarin may result in elevated INR. In case reports, elevated INRs occurred between 1 and 16 days of etoposide-chemotherapy regimens in 3 patients on warfarin. Symptoms included trace guaiac-positive black stools and bruising at the site of blood draws in 1 patient, no bleeding or bruising in another patient, and subconjunctival hemorrhage in the third patient on warfarin . Monitor INR frequently during concomitant use .

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Concomitant use of etoposide and warfarin may result in elevated INR. Monitor INR frequently during concomitant use.

Mechanism Of Interaction

Unknown

Literature Reports

A) A 74-year-old man stabilized on warfarin for atrial fibrillation had an elevated INR of 12.6, a decreased hemoglobin, and experienced trace guaiac-positive black stools and bruising at the site of blood draws 16 days after a cycle of carboplatin and etoposide. His INR had been stable for 8 months (1.15 to 2.11) while on warfarin 5 mg every other day alternating with 7.5 mg every other day. He subsequently required carboplatin 180 mg/m(2) IV on day 1 plus etoposide 150 mg/m(2) IV on days 1 to 3 for secondary mediastinal metastases. Two days prior to chemotherapy his INR was 2.11, hemoglobin 12.6 g/dL, and platelets 228 x 10(3)/mm(3). On follow-up visit 11 days post-chemotherapy, there was no evidence of bleeding or symptoms of nausea, vomiting, fever, or chills. INR was not measured at the time, but hemoglobin was 11.1 g/dL. On post-chemotherapy day 16, he was admitted to the hospital with fever, diarrhea, nausea, and vomiting. His INR was 12.6, hemoglobin 10.5 g/dL, and platelets 348 x 10(3)/mm(3). He had trace guaiac-positive black watery stools and bruises at the site of blood draws. Warfarin was stopped for 2 days and he was administered phytonadione IV and fresh frozen plasma. Due to suspected gastrointestinal bleeding, decreased hemoglobin, and his history of cardiac and pulmonary disease, packed red blood cells were administered. All subsequent INRs were below 2. The patient refused further chemotherapy .

B) A 78-year-old man on warfarin experienced elevated prothrombin times (PT) within 24 hours of etoposide and vindesine administration; elevated prothrombin times occurred in 3 out of the 4 chemotherapy cycles. No bleeding or bruising were reported. After the second chemotherapy cycle, the PT increased to 29, 29, and 23 seconds from 21.3 seconds despite warfarin 5 mg interruption those 3 days. After the third cycle, the PT increased 30, 32, and 30 seconds from 21 seconds despite warfarin 2.5 mg interruption those 3 days. After the fourth cycle, the PT increased 31.3, 35.4, and 30.3 seconds from 20.7 seconds despite warfarin 2.5 mg interruption those 3 days. Chemotherapy was discontinued and for the next 82 days until his death warfarin 2.5 mg was continued .

C) After starting warfarin, a 62-year-old man treated with cyclophosphamide, doxorubicin, etoposide, mechlorethamine, vincristine, procarbazine, methotrexate, and prednisone for lymphoma experienced elevated prothrombin times (PT) on days 1 and 8 and subconjunctival hemorrhage on day 1. His PT ranged from 18 to 20 sec with a stable warfarin dose. The PT increased to 45, 30, and 36 sec, respectively, on 3 subsequent cycles after day 1 and 8 of chemotherapy. The PT returned to normal within 1 week of discontinuation of warfarin .

Warfarin Overview

• Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.

Etoposide Overview

• Etoposide is used in combination with other medications to treat a certain type of lung cancer (small cell lung cancer; SCLC). Etoposide is in a class of medications known as podophyllotoxin derivatives. It works by slowing or stopping the growth of cancer cells in your body.

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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.