Drug Interaction Report

Warfarin and Cyclophosphamide: Interaction Details

Name: Warfarin and Cyclophosphamide Interaction
Creator: Dr. Brian Staiger, PharmD, BCPS

A pharmacist-reviewed analysis of the Warfarin and Cyclophosphamide interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Warfarin

Coumadin Jantoven

Cyclophosphamide

Cytoxan® Frindovyx

Medically reviewed by

Dr. Brian Staiger, PharmD, BCPS

Updated Aug 8, 2026

Editorial policy · Data sources

Interaction severity

Major

Potentially serious — often needs a change or close monitoring.

Minor

Moderate

Major

Contraindicated

How we grade severity & evidence

Severity levels

Contraindicated: These should generally not be used together.
Major: Potentially serious — often needs a change or close monitoring.
Moderate: Can be significant — usually manageable with monitoring.
Minor: Usually limited clinical impact.

Evidence grades

Established: Well documented — supported by controlled studies or strong clinical data.
Probable: Good supporting evidence, though not definitively proven.
Suspected: Some evidence suggests this interaction, but it is not well established.
Possible: Limited or conflicting evidence; the interaction may occur.
Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 210 documented Warfarin interactions, 160 are rated major — including this one.

Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.

Onset

unspecified

Evidence

probable

Severity

Major

What happens

Increased risk for elevated INR and subsequent bleeding

Interaction Deep Dive

Elevated prothrombin time was experienced within 1 day in 1 patient and within 15 days in 2 patients treated with a cyclophosphamide-chemotherapy regimen and concomitant warfarin. Patients experienced 1 or more symptoms of gross hematuria, microscopic hematuria, epistaxis, and/or subconjunctival hemorrhage². The manufacturers do not identify cyclophosphamide, methotrexate, fluorouracil, etoposide, doxorubicin, mechlorethamine, vincristine, or procarbazine as drugs that interact with warfarin ³¹⁴⁵⁶⁷⁸⁹¹⁰. Monitor the INR (international normalized ratio) closely and monitor for signs of bleeding when warfarin is used concomitantly with cyclophosphamide-chemotherapy regimens. Warfarin dosage may require adjustment to maintain the desired level of anticoagulation.

Why it happens (mechanism)

Unknown

Literature reports

3 reports — tap to read

a) After starting warfarin, a 70-year-old woman treated with cyclophosphamide, methotrexate, and fluorouracil for breast cancer experienced elevated prothrombin times (PT) by day 15 on 4 chemotherapy cycles; furthermore, she experienced gross hematuria on the first occasion and epistaxis on each occasion. Her PT ranged from 8.2 to 21 sec with a stable warfarin dose. The PT increased to 44.2, 39, 31, and 29 sec, respectively, by day 15 of each subsequent cycle of chemotherapy. The PT returned to pre-treatment levels within 48 to 72 hours. Epistaxis and hematuria responded to discontinuation and reduction of warfarin dosage ².

b) After starting warfarin, a 57-year-old woman treated with cyclophosphamide, methotrexate, and fluorouracil for breast cancer experienced elevated prothrombin times (PT) and microscopic hematuria by day 15 of each cycle. She also experienced epistaxis on 1 occasion. Her PT ranged from 14.8 to 17.2 sec over 3 weeks. The PT increased to a range of 24.6 to 26 sec by day 15 of each subsequent cycle of chemotherapy. The PT returned to pre-treatment levels within 48 hrs ².

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 ².

Common questions

Can I take Warfarin and Cyclophosphamide together?

Increased risk for elevated INR and subsequent bleeding Always confirm with your pharmacist or prescriber before making any change.

How serious is the Warfarin and Cyclophosphamide interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

Does my dose of Warfarin or Cyclophosphamide need adjusting while I take them together?
What symptoms should prompt me to call you or my prescriber right away?
Does the timing of my doses matter for this combination?
Is there a safer alternative to one of these medications for me?

References (10)

Product Information: CYTOXAN(R) injection, oral tablets, cyclophosphamide injection, oral tablets. Bristol-Myers Squibb Company, Princeton, NJ, 2005.
Seifter EJ, Brooks BJ, & Urba WJ: Possible interactions between warfarin and antineoplastic drugs. Cancer Treat Rep 1985; 69(2):244-245.
Product Information: COUMADIN(R) oral tablets, IV injection, warfarin sodium oral tablets, IV injection. Bristol-Myers Squibb Company, Princeton, NJ, 2007. DailyMed
Product Information: methotrexate oral tablets, methotrexate oral tablets. Roxane Laboratories,Inc, Columbus, OH, 2006. DailyMed
Product Information: fluorouracil iv injection, fluorouracil iv injection. Sicor Pharmaceuticals Inc. Irvine, CA, 1999.
Product Information: ETOPOPHOS(R) injection, etoposide phosphate. Bristol-Myers Squibb Company, Princeton, NJ, 2004. DailyMed
Product Information: MATULANE(R) capsules, procarbazine hydrochloride capsules. Sigma-Tau Pharmaceuticals Inc. Gaithersburg, MD, 2004. DailyMed
Product Information: vincristine sulfate injection, vincristine sulfate injection. Mayne Pharma (USA) Inc. Paramus, NJ, 2004. DailyMed
Product Information: MUSTARGEN(R) injection, mechlorethamine hcl injection. Merck & Co. Whitehouse Station, NJ, 2004. DailyMed
Product Information: RUBEX(R) injection, doxorubicin hydrochloride injection. Mead Johnson, Princeton, NJ, 2001. DailyMed

Was this write-up helpful?

Warfarin

Keep reading about Warfarin

All Warfarin interactions (210)

Also serious with: Defibrotide Injection Penicillin V Potassium Ofloxacin Otic Cefixime

Cyclophosphamide

Keep reading about Cyclophosphamide

All Cyclophosphamide interactions (88) Cyclophosphamide drug information

Also serious with: Varicella Virus Vaccine, Live Yellow Fever Vaccine Dengue Tetravalent Vaccine, Live Bacillus Of Calmette And Guerin Vaccine, Live

Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Warfarin + Activated Charcoal Alfalfa American Ginseng Beer Cannabis Danshen Dong Quai Fasting + 353 more

Cyclophosphamide + Activated Charcoal Beer Grapefruit Siberian Cocklebur St. John's Wort Wine Acacia Rigidula Acerola + 212 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

Still have questions about this combination?

Every question gets a real answer from a licensed pharmacist — free, and usually within a day.

Ask the pharmacist

A message from HelloPharmacist

About our interaction database: depth, not breadth

HelloPharmacist doesn't license one of the big commercial interaction databases, so what you'll find here is not a complete list of every known drug interaction. Instead, each entry is researched, analyzed, and written up individually — documented from the published literature, reviewed by a pharmacist, and cited so you can check every source yourself.

If a combination isn't listed here, it means we haven't documented it yet — never that it's safe. For screening a full medication list, we recommend pairing this site with a comprehensive tool like the Drugs.com Interaction Checker and, most importantly, a review by your own pharmacist. For a deep, plain-English, fully sourced explanation of a specific documented interaction — that's exactly what we built this for.

This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.