What is methotrexate?

Methotrexate is a type of disease-modifying anti-rheumatic drug (DMARD). It’s used to reduce activity of the immune system for people who have certain conditions.

The immune system normally protects the body from infections by causing inflammation to fight them. Inflammation can cause swelling, heat, redness and pain.

But in some conditions, the immune system can attack parts of the body, such as the joints, by mistake causing illness.

How is methotrexate used?

Methotrexate can be given to people with various types of arthritis and related conditions, including:

It can also be given to children who have:

Methotrexate treats the symptoms of your condition and reduces the risk of uncontrolled inflammation causing long-term damage to your  joints.

It can take a while to start working, so it could be up to 12 weeks before you start to notice any difference, but you should still keep taking it. You will need to carry on taking methotrexate even when your symptoms improve and you are feeling better.

Methotrexate is also used by doctors to treat other conditions, such as cancer, but the dose used for cancer is usually much higher than for arthritis and related conditions.

Is methotrexate suitable for me?

Before you can start methotrexate, your doctor will need to make sure it is the right drug for you by checking if:

  • you’re pregnant or planning a family
  • you’re breastfeeding
  • you have an infection
  • you have a liver or kidney disease
  • you’ve had a recent vaccination
  • you've had severe mouth ulcers
  • you’ve had ulcers in the stomach or bowel.

If you have side effects from taking methotrexate, speak to your doctor as you might not be able to carry on taking it. Side effects can happen immediately or after you have taken methotrexate for a long time, but mild ones often settle over time.

How and when is methotrexate taken?

Methotrexate can be taken as a tablet, liquid or injection.

Methotrexate should be taken on the same day once a week. You’ll be given a starting dose of methotrexate while your rheumatologist tries to bring your condition under control, but this might be increased if it isn’t helping your symptoms.

Methotrexate tablets come in two strengths: 2.5 mg and 10 mg. To avoid confusion, it’s recommended you only be given one strength, usually 2.5mg. If you are prescribed both tablet strengths be very careful not to confuse them, as they can look quite similar.

If you are starting methotrexate injections, you'll usually be given your methotrexate injection by a health professional. They will often show you how to inject yourself using either a syringe or injector pen, so you can do it at home. Let them know if you think you will have difficulty injecting yourself.

You must always wash your hands before and after handling methotrexate.

Side effects and risks

Methotrexate can sometimes cause side effects, which may include:

  • feeling sick
  • headaches
  • vomiting
  • diarrhoea
  • shortness of breath
  • mouth ulcers
  • minor hair loss and hair thinning
  • rashes.

If you're concerned by any side effects, contact a health professional for advice.

It’s very important that you have blood tests to check your blood count, kidney and liver function before starting methotrexate. You will have regular blood tests while you’re taking it, as methotrexate can affect your liver and cause your body to make fewer blood cells.

At first, you'll need to have blood tests every two weeks. Once you are on a stable dose of methotrexate you should only need tests every two to three months for as long as you are taking it.

Before starting treatment, you may have a chest x-ray and breathing tests to check your lung function. Depending on your general health, your doctor may want to run some other tests to make sure you can take methotrexate.

If you smoke, it’s worth cutting down or preferably giving up, as smoking increases your risk of complications with your condition and its treatments.

Because your condition and methotrexate affect the immune system, you may be more likely to get infections. If you get an infection, or you're taking antibiotics, ask your nurse specialist or doctor for advice about whether it will affect your weekly dose of methotrexate.

Tell your doctor or nurse specialist straight away if you start to feel really unwell or if you experience any of the following:

  • a sore throat
  • raised temperature or fever
  • flushing or sweating
  • sores in your mouth
  • tummy ache
  • feeling or being sick
  • changes to your urine and how often you pee
  • a cough
  • loss of appetite
  • unexplained bruising or bleeding
  • yellowing of the skin or eyes, known as jaundice
  • any new symptoms or anything else that concerns you.

Methotrexate can cause breathlessness. If this happens to you, see your doctor, as in rare cases it can cause inflammation of the lungs.

You should also contact your doctor urgently if you develop chickenpox or shingles, or come into contact with someone who has chickenpox or shingles. These infections can sometimes be very serious in people who are taking methotrexate.

You might need treatment against chickenpox or shingles, and you might be told to stop taking methotrexate until you’re better.

If you think you may have an infection a healthcare professional will be able to advise you on how best to treat it when you're taking methotrexate.

Tips to reduce your risk of infection

  • Try to avoid close contact with people you know have an infection.
  • Wash your hands regularly and carry around a small bottle of antibacterial hand gel.
  • Keep your mouth clean by brushing your teeth regularly.
  • Stop smoking if you’re a smoker.
  • Make sure your food is stored and prepared properly.
  • Try to keep your house clean and hygienic, especially the kitchen, bathrooms and toilets.

Often, people say methotrexate upsets their tummy or makes them sick. Your doctor will probably give you folic acid tablets to help reduce any unpleasant effects caused by your weekly dose of methotrexate. They will tell you when to take the folic acid. Generally, you should avoid taking it on the same day as methotrexate, because it can affect how well the methotrexate works.

If you are still having problems speak to your doctor about any additional treatments that could help reduce these effects. You should not use over-the-counter drugs to treat them yourself.

Taking other medicines

Methotrexate can sometimes be given along with other drugs to treat your condition. You can usually carry on taking painkillers like paracetamol if needed, unless your doctor advises otherwise.

Avoid taking non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin or ibuprofen, or medicines containing NSAIDs, such as over-the-counter cold medication, without first speaking to your doctor.

Check with your doctor before taking any new drugs, and remember to mention you’re on methotrexate if you’re treated by anyone other than your usual doctor or nurse specialist.

There are several types of drugs that react with methotrexate and should be avoided if possible. These include:

  • some antibiotics such as those containing trimethoprim, co-trimoxazole, tetracyclines, ciprofloxacin, and some forms of penicillin
  • some asthma medications including theophylline
  • some epilepsy medicines such as phenytoin and levetiracetam
  • some medicines used to treat indigestion, known as proton pump inhibitors (PPI), such as omeprazole
  • diuretics, used to help you pee more, such as indapamide and benroflumenthiazide
  • over-the-counter preparations or herbal remedies.

You should always check whether any medication or over-the-counter preparation you intend to take could affect your methotrexate treatment.


Depending on the dose of methotrexate and what other drugs you’re taking, you may need to avoid live vaccines.

Speak to your doctor if you think you might need a live vaccine against illnesses such as Bacillus Calmette-Guérin (BCG), typhoid, yellow fever, or the mumps, measles and rubella (MMR) vaccine.

The pneumonia vaccine and yearly flu vaccines, usually given to adults, are not live vaccines and don’t affect methotrexate, so it’s recommended that you have these.

If you haven't had chickenpox,  you may be offered a vaccine against it before you start treatment. The chickenpox vaccine may also be offered to people living with you before you start treatment, if they haven't had the virus.

You should stay away from anyone who has had the live oral polio vaccine, for six weeks, if you’re taking methotrexate. If you have a baby and you’re taking methotrexate ask your doctor whether your child should have the inactive version of the vaccine.

If you’re offered a shingles vaccination you should speak to your rheumatology team before having it, as even though this is a live vaccine, you might still be able to have it if you’re on a low dose of methotrexate.

However, other treatments that affect your immune system, such as steroids, may prevent you from having these vaccines. Check with your rheumatology team if you’re unsure.

Children and vaccines

It’s generally recommended that children who are taking methotrexate avoid live vaccines. Many of the vaccines in the routine childhood immunisation programme, as well as the annual flu vaccine, can be given as inactivated, or non-live, vaccines. If you are unsure about whether your child can have a vaccination if they are taking methotrexate, ask a healthcare professional for advice.

Having an operation

If you’re due to have surgery, ask your doctor whether it will affect your routine methotrexate treatment.


Alcohol and methotrexate can both affect your liver, so it’s important you don’t drink more alcohol than the government’s recommended limits.

The government guidelines say both men and women should have no more than 14 units of alcohol a week, and that you should spread these through the week rather than having them all in one go.

You can find out more about units of alcohol at drinkaware.

Some rheumatologists may suggest stricter limits. If you’re concerned, discuss your alcohol intake with your healthcare team.

Fertility, pregnancy and breastfeeding

Women using this drug should use contraception or encourage their partner to. Talk to your doctor as soon as possible if you’re planning to start a family.

You shouldn't take methotrexate if you're pregnant or trying for a baby, as it can affect how an unborn baby develops.

Methotrexate should be stopped three months before you become pregnant. If you become pregnant while taking methotrexate or if you've had less than a three-month break from the drug, it's important to speak to your doctor as soon as possible.

It used to be recommended that men stop methotrexate three months before trying for a baby, but research now shows it's fine for men to continue taking methotrexate when trying for a baby with their partner.

If you are planning to try for a baby it's important to take folic acid to support the health of you and your baby.

You shouldn’t breastfeed if you’re on methotrexate, as the drug could pass into breast milk, and we yet don’t know what effects this could have on a baby.

Your doctors will usually recommend going straight back onto methotrexate once you’ve finished breastfeeding. This is because the sooner you can get back onto your medication, the lower the risk of having a flare.