Can I take Warfarin and Methotrexate together?

Taking warfarin and methotrexate together should be done with caution as taking them together can significantly increase your risk of bleeding.

You must speak to your doctor before taking these together. If you are prescribed both, you will need much more frequent blood tests (INR) to monitor how quickly your blood clots.

Why this happens

Methotrexate can displace warfarin from the proteins in your blood that normally carry it, leaving more 'active' warfarin to thin your blood.

Additionally, methotrexate can sometimes affect how the liver processes warfarin and may cause damage to the lining of the stomach or gut, which increases the risk of a bleed starting.

How to know if you're having a drug interaction

You may be experiencing an interaction between warfarin and methotrexate if:

• You notice unusual bruising or bleeding, such as nosebleeds or bleeding gums.

• You have blood in your pee (urine) or poo (stools), or have black, tarry poo.

• You feel unusually tired, weak, or dizzy.

• You develop mouth ulcers or a sore throat.

• You have signs of infection, such as fever or chills.

• Your blood tests show a raised INR or changes in blood counts.

What you should do

If you have any of the above symptoms, you should:

• Contact your GP or anticoagulation clinic for advice as soon as possible.

• Seek urgent medical help if you have heavy bleeding or bleeding that will not stop.

• Do not stop taking warfarin or methotrexate suddenly unless advised by a healthcare professional.

• Attend any blood tests arranged to check your INR or blood counts.

Tell your healthcare professional about all medicines, supplements, and herbal remedies you are taking.

Important precautions

Bleeding risk

Warfarin increases your risk of serious bleeding. You must seek immediate medical attention if you have a fall, a head injury, or notice signs of internal bleeding such as dark/tarry stools or coughing up blood.

Drug interactions (NSAIDs)

Do not take anti-inflammatory painkillers like ibuprofen or aspirin unless specifically prescribed. These can dangerously increase the levels of methotrexate in your blood or significantly increase your risk of a major bleed while on warfarin.

Pregnancy and conception

Methotrexate causes severe birth defects and miscarriage. Both men and women must use effective contraception during treatment and for at least 6 months after stopping. If you think you are pregnant, seek medical advice immediately.

Warfarin can cause serious harm to an unborn baby. You must use effective contraception while taking it and inform your doctor immediately if you think you are pregnant.

Infection and blood disorders

Methotrexate can suppress your immune system and bone marrow. You must report a sore throat, fever, or unexplained bruising/bleeding immediately, as these can be signs of life-threatening blood toxicity or infection.

Lung and Liver Toxicity - methotrexate

Contact your doctor immediately if you develop a persistent dry cough or shortness of breath, as this can indicate serious lung inflammation. Avoid alcohol as it increases the risk of liver damage.

Dosing Schedule

Methotrexate for inflammatory conditions must only be taken ONCE A WEEK on the same day. Taking it daily can be fatal.

Food and drink warnings

Alcohol

It is best to avoid or strictly limit alcohol while taking warfarin. Alcohol can affect how your liver processes the medicine, which may increase your risk of bleeding or cause your INR levels to become unstable. If you do drink, keep it to a minimum and do not binge drink.

It is best to avoid or strictly limit alcohol when taking methotrexate. Both methotrexate and alcohol can cause damage to the liver; combining them significantly increases the risk of serious liver toxicity.

Foods high in vitamin K (e.g. spinach, kale, broccoli, Brussels sprouts, asparagus)

Vitamin K helps your blood to clot, which works against warfarin. You do not need to avoid these foods entirely, but you must keep the amount you eat consistent. A sudden increase or decrease in vitamin K intake can change how well your warfarin works.

Caffeine (Coffee, Tea, Cola)

Large amounts of caffeine may reduce the effectiveness of methotrexate for certain conditions like rheumatoid arthritis. Monitor your symptoms if you consume high levels of caffeine.

Cranberry juice and Goji berries

Cranberry juice and goji berry products can significantly increase the blood-thinning effect of warfarin, leading to a higher risk of bruising or bleeding. It is best to avoid these while taking warfarin.

Grapefruit juice

Grapefruit juice may increase the levels of warfarin in your blood, which can increase your risk of bleeding. It is best to avoid grapefruit juice.

Pomegranate juice

Some evidence suggests pomegranate juice may interact with warfarin and increase the risk of bleeding. It is best to avoid it.

Folic Acid (Vitamin B9) and Fortified Foods

While your doctor will likely prescribe a folic acid supplement to reduce side effects, you should avoid taking additional over-the-counter multivitamins containing folic acid or eating excessive amounts of foods highly fortified with folic acid without consulting your specialist, as it can interfere with how the medicine works.

Using other medicines

Taking multiple medicines? Our Medicines Interaction Checker helps you check whether your prescriptions, over-the-counter medicines, and supplements are safe to take together. Simply search for your medicines to see potential interactions and what to do about them.

Disclaimer

This information is for general educational purposes only and should not be relied upon as a substitute for professional medical advice. Always consult your GP, pharmacist, or another qualified healthcare professional before making decisions about your medications. Individual circumstances may vary, and only a healthcare professional who knows your medical history can provide personalised guidance.