Methotrexate is a type of chemotherapy. It's a treatment for a number of different types of cancer.

How does methotrexate work?

Methotrexate works by destroying quickly dividing cells, such as cancer cells.

How you have methotrexate

How you have methotrexate depends on what type of cancer you have. You can have it as: 

  • an injection into your bloodstream (intravenous)
  • a tablet or a liquid you can drink (solution)
  • an injection into your muscle 
  • an injection into your spinal fluid (intrathecal injection)

You might have another drug called folinic acid after methotrexate. It helps normal cells recover and reduces side effects.

Into your bloodstream

You might have treatment through a long plastic tube that goes into a large vein in your chest. The tube stays in place throughout the course of treatment. This can be a:

  • central line
  • PICC line
  • portacath

Taking your tablets or liquid

You must take tablets and liquid according to the instructions your doctor or pharmacist gives you. 

You should take the right dose, not more or less.

Never stop taking a cancer drug without talking to your specialist first.

Injection into your muscle (intramuscular)

You have the injection into a muscle, usually into your buttock or upper thigh.

Injection into your spinal fluid

Your doctor injects the drug into the fluid around your spinal cord Open a glossary item during a lumbar puncture Open a glossary item. The side effects may be less with this way of having methotrexate. Side effects include:

  • a headache
  • high temperature (fever)
  • stiff neck
  • back or shoulder pain
  • sleepiness
  • temporary muscle weakness
  • temporary loss of movement in some parts of your body 
  • temporary shaking (tremor)
  • irritability and confusion
  • difficult or unclear speech
  • confusion and loss of memory
  • problems with walking and balance
  • drowsiness
  • fits (seizures)
  • swelling in the brain
Contact your advice line, doctor or nurse if you have any of these side effects.

How often do you have methotrexate?

You usually have it as a course of several cycles of treatment Open a glossary item. Each cycle varies depending on what type of cancer you have. Your doctor or nurse will tell you more about this. 


You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver and kidneys are working.

What are the side effects of methotrexate?

Side effects of treatment will depend on the amount you have (the dose) and how you have the drug.

We haven't listed all the side effects. Your doctor or nurse will talk to you about the possible side effects. Tell them if you notice anything unusual or different during and after treatment.

When to contact your team

Your doctor and nurse will monitor you closely for any side effects. Let them know as soon as possible if:

  • you have severe side effects 
  • your side effects aren’t getting any better
  • your side effects are getting worse

Early treatment can help manage side effects better. 

Contact your doctor or nurse immediately if you have signs of infection, including a temperature above 37.5C.

Common side effects

These side effects happen in more than 10 in 100 people (more than 10%). You might have one or more of them. They include:

Increased risk of infection

Increased risk of getting an infection is due to a drop in white blood cells. Symptoms include a change in temperature, aching muscles, headaches, feeling cold and shivery and generally unwell. You might have other symptoms depending on where the infection is.

Infections can sometimes be life threatening. You should contact your advice line urgently if you think you have an infection. 

Bruising, bleeding gums and nosebleeds

This is due to a drop in the number of platelets in your blood. These blood cells help the blood to clot when we cut ourselves. You may have nosebleeds or bleeding gums after brushing your teeth. Or you may have lots of tiny red spots or bruises on your arms or legs (known as petechiae).

Allergic reaction

An allergic reaction that can cause a rash, shortness of breath, redness or swelling of the face and dizziness. Some allergic reactions can be life threatening. Alert your nurse or doctor if notice any of these symptoms.

Mouth sores and ulcers

Mouth sores and ulcers can be painful. It helps to keep your mouth and teeth clean, drink plenty of fluids and avoid acidic foods such as lemons. Chewing gum can help to keep your mouth moist. Tell your doctor or nurse if you have ulcers.

Liver changes

You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes. You have regular blood tests to check for any changes in the way your liver is working.

Rarely, you might have inflammation or scarring of the liver needing treatment.

Indigestion or heartburn

Contact your doctor or pharmacist if you have indigestion or heartburn. They can prescribe medicines to help.

Tummy (abdominal) pain

Tell your treatment team if you have this. They can check the cause and give you medicine to help. 

Feeling or being sick

Feeling or being sick is usually well controlled with anti sickness medicines. It might help to avoid fatty or fried foods, eat small meals and snacks and take regular sips of water. Relaxation techniques might also help.

It is important to take anti sickness medicines as prescribed even if you don’t feel sick. It is easier to prevent sickness rather than treat it once it has started.

Loss of appetite

You might not feel like eating and may lose weight. Eating several small meals and snacks throughout the day can be easier to manage. You can talk to a dietitian if you are concerned about your appetite or weight loss. 

Kidney changes

You might have some changes in the way your kidneys work. You have regular blood tests to check how well they are working.

Occasional side effects

These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%). You might have one or more of them. They include:

  • breathlessness and looking pale due to a drop in red blood cells (anaemia)
  • tiredness (fatigue) or drowsiness
  • headaches
  • dizziness – do not drive or operate machinery if you are drowsy or dizzy
  • diarrhoea
  • skin changes such as a rash, itching or reddening of the skin
  • thickening and scarring of the lung tissue causing a cough and shortness of breath
  • hair loss - usually with higher doses of methotrexate, for example lymphoma or acute lymphoblastic leukaemia (ALL)

Rare side effects

These side effects happen in fewer than 1 in 100 people (fewer than 1%). You might have one or more of them. They include:

  • confusion
  • shifts in your mood (mood swings) or feeling very low (depression)
  • high blood sugar levels (diabetes)
  • your skin and eyes being very sensitive to sunlight
  • muscle and joint pain
  • weakening of the bones (osteoporosis)
  • heart problems such as build up of fluid around the heart
  • ulcers and swelling (inflammation) of the stomach, bowel, bladder or vagina
  • fits (seizures)
  • feeling like the room is spinning (vertigo)
  • weakness on one side of your body
  • a severe skin reaction that may start as tender red patches which leads to peeling or blistering of the skin. You might also feel feverish and your eyes may be more sensitive to light. This is serious and could be life threatening
  • a second cancer called lymphoma
  • low blood pressure
  • blood clots that can be life threatening; signs are pain, redness and swelling where the clot is. Feeling breathless can be a sign of a blood clot in the lung. Contact your advice line or doctor straight away if you have any of these symptoms
  • inflammation of the pancreas (pancreatitis) – symptoms include severe tummy pain, feeling or being sick, a high temperature or you may have loose poo
  • slow wound healing
  • changes to the levels of chemicals in your blood due to the breakdown of tumour cells (tumour lysis syndrome) - you have regular blood tests to check for this
  • skin sensitive to sunlight (photosensitivity). Cover up, wear a hat and use sunscreen when you go out in the sun

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do I need to know?

Other medicines, foods and drink 

Cancer drugs can interact with some other medicines and herbal products. Tell your doctor or pharmacist about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies.

It is important to drink plenty during treatment for methotrexate. If you become dehydrated you may increase the side effects of the drug. 


Avoid drinking alcohol while having methotrexate.

Pregnancy and contraception

This treatment might harm a baby developing in the womb. It is important not to become pregnant or father a child while you're having treatment and for up to 6 months afterwards. Talk to your doctor or nurse about effective contraception before starting treatment.


Don’t breastfeed during this treatment because the drug may come through into your breast milk.

Loss of fertility

You may not be able to become pregnant or get someone pregnant after treatment with this drug. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Men might be able to store sperm before starting treatment. And women might be able to store eggs or ovarian tissue. But these services are not available in every hospital, so you would need to ask your doctor about this.    

Treatment for other conditions

If you are having tests or treatment for anything else, always mention your cancer treatment. For example, if you are visiting your dentist.


Don’t have immunisations with live vaccines while you’re having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having. Ask your doctor or pharmacist how long you should avoid live vaccinations.

In the UK, live vaccines include rubella, mumps, measles, BCG, yellow fever and one of the shingles vaccines called Zostavax.

You can have:

  • other vaccines, but they might not give you as much protection as usual
  • the flu vaccine (as an injection)
  • the coronavirus (COVID-19) vaccine - talk to your doctor or pharmacist about the best time to have it in relation to your cancer treatment

Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine. This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system Open a glossary item recovers from treatment.

Contact with others who have had immunisations - You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If this happens they should keep the area covered.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray as this is a live vaccine. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn't possible, wash your hands well after changing their nappy.

More information about this treatment

For further information about this treatment and possible side effects go to the electronic Medicines Compendium (eMC) website. You can find the patient information leaflet on this website.

You can report any side effect you have to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.

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