Methotrexate

• Methotrexate is used to treat Crohn’s. Methotrexate is not usually used to treat Colitis.
• Methotrexate is only taken once a week. Never take methotrexate daily.
• It can take up to 12 weeks before you feel the benefits of methotrexate.
• Methotrexate changes the way your immune system works. This means that your body might not be able to fight off infections as well as it used to. Contact your GP or IBD team straight away if you think you have an infection.
• Avoid having live vaccines when taking methotrexate. The annual flu jab and all COVID jabs are non-live vaccines. These are safe to have if you are taking methotrexate.

The brand name for methotrexate tablets is Maxtrex.

The brand names for methotrexate injections include Metoject, Methofill, Zlatal and Nordimet.

You’ll also take folic acid tablets when on methotrexate. Folic acid helps reduce some of the possible side effects of methotrexate.

If you have Colitis

Methotrexate is not recommended for the maintenance treatment of Colitis.

But sometimes people with Colitis may be taking methotrexate. For example:

• To help manage another condition that you may also have, such as rheumatoid arthritis.
• If it is not clear whether you have Crohn's or you have Colitis.
• Alongside some other treatments, to increase the amount of time that you stay in remission.

Your IBD team will be able to give you clear advice on why methotrexate is being recommended to you as a treatment.

There are lots of things to think about when you start a new treatment. Your IBD team will discuss your options with you. When thinking about a new treatment you might want to consider the potential benefits, possible risks and the goals of your treatment. Some things to think about include:

• How you will take it.
• How well it works.
• How quickly it is likely to work.
• Side effects you might experience.
• Whether you need ongoing tests or checks.
• Other medicines you are taking.

Our Appointment guide has a list of questions you might want to ask. It can help you focus on what matters most to you. You might find our information about other medicines and surgery for Colitis helpful.

When treating Crohn’s or Colitis, the first aim of treatment is to get your symptoms under control. This is induction treatment. Once your symptoms are under control, the aim of treatment is to keep them under control. This is maintenance treatment.

Some clinical trials look at how well a medicine works as induction treatment. Some look at how well it works as maintenance treatment. Some look at how well it works for both.

Find out more about how we talk about the effectiveness of medicines.

Methotrexate in Crohn’s

For Crohn’s, we have information about how well methotrexate works for induction treatment and maintenance treatment separately.

Getting Crohn’s under control

These results come from a review that combines the results of several studies. The review compared methotrexate injection 25mg each week with dummy treatment (placebo). The table below shows how well methotrexate got Crohn’s under control after 16 weeks.

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After 16 weeks, twice as many people taking methotrexate had their Crohn’s under control compared with those who took placebo. About 39% (39 in every 100 people) who took methotrexate had their Crohn’s under control compared with 19% (19 in every 100 people) who took placebo.

People who took methotrexate needed less steroids to control their symptoms than those who took placebo. After 16 weeks, the people that took methotrexate needed 50% less steroid dose than those who took placebo.

Methotrexate can be as effective as azathioprine, another treatment for Crohn’s. One study compared methotrexate with azathioprine for getting Crohn’s under control. It found a similar amount of people in each group had their symptoms under control after 3 months and 6 months. People taking azathioprine had fewer side effects than those taking methotrexate.

Keeping Crohn’s under control

One study compared methotrexate 15mg each week with dummy treatment (placebo) for keeping symptoms under control. The people in the study were already in remission after initial treatment with methotrexate. The table below shows how well methotrexate kept their Crohn’s under control after 40 weeks.

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After 40 weeks, more people taking methotrexate had their Crohn’s under control than those who took placebo. About 65% (65 in every 100 people) who took methotrexate had their Crohn’s under control. About 39% (39 in every 100 people) who took placebo had their Crohn’s under control.

Fewer people taking methotrexate needed to take a course of steroids for a flare-up.

Methotrexate in Ulcerative Colitis

In people with Colitis, studies show that methotrexate is similar to placebo for induction and maintenance of remission.

Swallow the tablets with a glass of water. Do not chew or crush the tablets.

If you have methotrexate by injection, a nurse will usually give this to you. These will either be under the skin (subcutaneous) or into the muscle (intra-muscular). Your IBD team may train you on how to give yourself the injection.

If you forget to take your dose of methotrexate, speak to your pharmacist or doctor. You might be able to take the dose up to two days later but should not take it if you are three or more days late. If this happens, take your next dose on your usual day the following week.

Methotrexate is a long-term medicine. If it works for you, you may need to take methotrexate for months or even years.

You might take methotrexate at the same time as other treatments for your Crohn’s or Colitis. Your IBD team will discuss whether you need to take more than one treatment.

You may take methotrexate along with steroids during induction treatment. The steroid dose will go down once your symptoms are under control.

Methotrexate can also be taken along with anti-TNF treatment, such as adalimumab or infliximab. Giving methotrexate with an anti-TNF can increase the length of time you will be in remission.

Methotrexate can cause blood disorders. These include low white blood cells (leukopenia), low neutrophils (neutropenia) and low platelets (thrombocytopenia). Having low white blood cells or low neutrophils means you are more likely to get infections. Signs of infection include:

• A sore throat
• A high temperature
• Feeling very tired
• Mouth ulcers
• Muscle aches and pains

Having low platelets means your blood will not be able to clot easily. This means you might bleed or bruise more easily than usual. Keep an eye out for any unexplained bleeding or bruising.

Methotrexate can also affect your lungs. Let your IBD team know immediately if you have any:

• Shortness of breath or trouble breathing
• A dry cough that does not go away
• Chest pain

Methotrexate treatment may make your skin more sensitive to the sun. Exposure to the sun can cause a severe reaction that looks and feels like sunburn. Exposed skin may develop a rash, redness, swelling, blisters, red bumps or oozing wounds. If the reaction is severe the skin can become infected.

Infections

Methotrexate can weaken your immune system. This means your body can struggle to fight off infections. Be cautious around other people with infections. This includes chicken pox, shingles and COVID-19.

Bleeding or bruising

Methotrexate can lower the platelets in your blood. Platelets help your blood stick together and form a clot when you bleed. When you have low platelets, you are at risk of bleeding or bruising easily.

Common side effects

Common side effects can affect between 1 in 10 people to 1 in 100 people. The common side effects of methotrexate include:

• Tiredness
• Headaches
• Diarrhoea
• Feeling sick (nausea)
• Ulcers in the mouth
• Stomach pain
• Losing your appetite
• Heartburn
• Itchy skin or rash

These side effects can be temporary and go away with time. If they cause too much discomfort, speak to your doctor.

Less common side effects

Less common side effects can affect less than 1 in 100 people. The less common side effects of methotrexate include:

• Mood changes, such as depression
• Feeling confused
• Dizziness
• Being sick (vomiting)
• Hair loss

If these side effects do not disappear, speak to your IBD team.

This is not a full list of side effects. For more information see the Patient Information Leaflet provided with your medicine. Or visit medicines.org.uk/emc/. 

The safety of any new medicine will continue to be monitored after it has become available for use. This is done through longer term clinical studies and reporting of side effects. We encourage you to report any side effects to the Medicines and Healthcare Products Regulatory Agency (MHRA). You can do this through the Yellow Card scheme online. Or by downloading the MHRA Yellow Card app (yellowcard.mhra.gov.uk). This helps collect important safety information about medicines.

Live vaccines are made using weakened versions of living viruses or bacteria. If you have a lowered immune system, there is a possibility they might cause infections. Live vaccines used in the UK include:

• TB vaccine.
• Shingles vaccine – but a non-live version is also available.
• Chickenpox vaccine.
• Measles, mumps and rubella vaccines.
• Nasal flu vaccine used in children – but the injected flu vaccine used in adults is not live.
• Rotavirus vaccine.
• Yellow fever vaccine.
• Oral typhoid vaccine – but the injected typhoid vaccine is not live.

If someone you live with is due to have a live vaccine, ask your IBD team whether you need to take any precautions.

The adult flu vaccine is an inactivated vaccine. This is safe to use when taking methotrexate. The nasal flu vaccine used in children contains the weakened live virus. Speak to your child’s doctor or IBD team to discuss how they can be protected from the flu.

The annual flu jab and the pneumococcal and COVID-19 vaccines are not live vaccines. They are safe to have while you are taking methotrexate.

If you have Crohn’s or Colitis, you are more at risk of getting serious complications if you get the flu. It’s important to get your flu vaccine each year when it becomes available.

All types of the COVID-19 vaccine do not contain a live virus. These vaccines are currently recommended if you have a weakened immune system.

Speak to your IBD team if you are unsure about having any vaccines.

Methotrexate can harm an unborn baby or cause a miscarriage. Your doctor will make sure you are not pregnant before you start treatment. If you stop methotrexate treatment, try to avoid getting pregnant for 6 months after. This is because the medicine can still be in your blood.

If you could get pregnant, you will be advised to use reliable contraception while taking methotrexate. Methotrexate does not interact with the morning after pill (emergency contraceptive pill) or other contraceptive pills.

Speak to your IBD team if you are planning on becoming pregnant while on methotrexate. They’ll help you go through your possible options of treatment. Speak to your specialist if you become pregnant while taking methotrexate.

In the past, men were advised not to try and start a family while taking methotrexate or for 3 months after stopping. There are now several studies that show no increase in harm to babies born where the father was taking methotrexate at conception. Some healthcare professionals still advise waiting for 3 months after you have stopped methotrexate. If your condition is under control and you are worried about stopping treatment, discuss your options with your IBD team.

We have separate information about Reproductive health and  Pregnancy and birth.

We follow strict processes to make sure our information is based on up-to-date evidence and easy to understand.

Please email us at evidence@crohnsandcolitis.org.uk if:

• You have any comments or suggestions for improvements
• You would like more information about the sources of evidence we use
• You would like details of any conflicts of interest

You can also write to us at Crohn’s & Colitis UK, 1 Bishop Square, Hatfield, AL10 9NE, or contact us through our Helpline: 0300 222 5700