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Can I take Methotrexate and Paracetamol together?

Drug interaction guide

Taking paracetamol while on methotrexate is generally safe at standard doses, but there is a small risk that it could increase the levels of methotrexate in your blood or increase the strain on your liver. This is more likely to be a concern if you are taking high doses of methotrexate (usually for cancer) rather than the lower doses used for conditions like rheumatoid arthritis or psoriasis.

It is generally considered safe to take methotrexate and paracetamol (tylenol) together, however caution is needed with high doses or long-term use, as both can affect the liver and increase the risk of liver damage.

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Why this happens

Both drugs are processed by the liver, and paracetamol may slightly interfere with how the kidneys remove methotrexate from the body. If methotrexate levels rise too high, it can lead to side effects.

Additionally, both drugs can affect liver function, so taking them together requires monitoring.

  • You can usually take paracetamol with methotrexate, but you must stay within the recommended daily dose of paracetamol (no more than 4,000mg or eight 500mg tablets in 24 hours).

  • Always inform your doctor if you are taking paracetamol regularly, as they may want to monitor your liver function tests more closely.

  • If you notice yellowing of the skin or eyes (jaundice), dark pee, or severe stomach pain, contact your doctor immediately.

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Pregnancy and conception

Methotrexate causes severe birth defects and miscarriage. You must use effective contraception during treatment and for at least 6 months after stopping. This applies to both men and women.

Infection and blood disorders

Methotrexate can suppress your immune system and bone marrow. You must seek immediate medical help if you develop a fever, sore throat, mouth ulcers, or unexplained bruising/bleeding.

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.

Check all other medicines (like cold and flu remedies) to ensure they do not also contain paracetamol, as accidental overdose can cause fatal liver failure.

Dosing Schedule

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

Alcohol

It is best to avoid or strictly limit alcohol when taking these medicines. Both methotrexate and paracetamol can affect your liver; combining them with alcohol significantly increases the risk of serious liver damage. For methotrexate specifically, your doctor may advise you to avoid alcohol entirely.

Caffeine (coffee, tea, cola)

High intake of caffeine may reduce the effectiveness of methotrexate for some conditions, such as rheumatoid arthritis. If you notice your symptoms worsening, you may need to limit your caffeine intake.

Dairy products

Milk and dairy products contain an enzyme called xanthine oxidase which can break down methotrexate in the digestive tract. To ensure you get the full dose, avoid consuming large amounts of dairy at the same time you take your methotrexate tablets.

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 methotrexate works.

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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.

Article history

The information on this page is written and peer reviewed by qualified clinicians.

  • 25 Jan 2026 | Originally published
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