Methotrexate is a chemotherapy drug used to treat many different cancers.

It is best to read this information with our general information about chemotherapy and the type of cancer you have.

Methotrexate is usually given into a vein but can also be given in other ways. You may have it as an outpatient or during a stay in hospital. Your cancer doctor or nurse will tell you how often you will have it.

Like all chemotherapy drugs, methotrexate can cause side effects. Some of the side effects can be serious, so it is important to read the detailed information below.

Your healthcare team can give you advice on how to manage any side effects. Tell your doctor or nurse straight away if you:

  • have a temperature
  • feel unwell
  • have severe side effects, including any we do not mention here.

Rarely, side effects may be life-threatening. Your cancer doctor or nurse can explain the risk of these side effects to you.

If you need medical attention for any reason other than cancer, always tell the healthcare staff that you are having this treatment.

What is methotrexate?

Methotrexate is a chemotherapy drug used to treat many different cancers.

This information should ideally be read with our general information about chemotherapy and the type of cancer you have.

How methotrexate is given

You will be given methotrexate in the chemotherapy day unit or during a stay in hospital. A chemotherapy nurse will give it to you. Methotrexate can be given in combination with other drugs.

During treatment, you usually see a cancer doctor, a chemotherapy nurse or a specialist nurse. This is who we mean when we mention doctor or nurse in this information.

Before or on the day of treatment, a nurse or a person trained to take blood (phlebotomist) will take a blood sample from you. This is to check that it is okay for you to have chemotherapy.

You will also see a doctor or nurse before you have chemotherapy. They will ask you how you have been feeling. If your blood results are alright on the day of your treatment, the pharmacist will prepare your chemotherapy. Your nurse will tell you when your treatment is likely to be ready.

Before you start, your nurse will give you anti-sickness drugs and sometimes a steroid. Methotrexate is then given in one of the following ways:

  • through a short, thin tube that the nurse puts into a vein in your arm or hand (cannula)
  • through a fine tube that goes under the skin of your chest and into a nearby vein (central line)
  • through a fine tube that is put into a vein in your arm and goes up into a vein in your chest (PICC line).

Your nurse can give you methotrexate as a slow injection or drip (infusion) into your cannula or line. They usually run the drip through a pump, which gives you the treatment over a set time. You will usually have fluids through a drip at the same time.

Methotrexate may also be given:

  • as an injection into a muscle (intramuscular injection)
  • as tablets
  • by injection into the fluid around the spinal cord (intrathecally)
  • by injection into an artery (inter-arterial injection), but this is rare.

Methotrexate by injection into the spinal fluid

Methotrexate can be given into the spinal fluid to allow the drug to reach the spinal cord and brain. This is called intrathecal chemotherapy.

The doctor numbs an area of skin over your spine with local anaesthetic. Then they gently insert a needle between two of the spinal bones. This is called a lumbar puncture. They inject the chemotherapy drug through this needle into the spinal fluid. Your cancer doctor and nurse will explain everything in advance so you know what to expect.

You may get a headache after a lumbar puncture. To help prevent this, you may need to lie flat for a few hours afterwards and drink plenty of fluids.

Your course of chemotherapy

You have chemotherapy as a course of several sessions (or cycles) of treatment over a few months. This will depend on the type of cancer you have. Your doctor or nurse will tell you more about this and the number of cycles you are likely to have.

When methotrexate is being given

Some people might have this side effect while they are having methotrexate:

The drug leaks outside the vein

If this happens when you’re having methotrexate, it can damage the tissue around the vein. This is called extravasation. If you have any stinging, pain, redness or swelling around the vein, tell the nurse straight away. Extravasation is not common but, if it happens, it’s important that it’s dealt with quickly.

Folinic acid rescue

A drug called folinic acid (leucovorin) is usually given 24 hours after starting methotrexate treatment to reduce the side effects. Folinic acid can be given into your cannula or line while you’re attached to a drip. You have it regularly with fluids until the methotrexate is out of your system.

Folinic acid is sometimes given as tablets. It is very important to take the tablets on time and to take them all exactly as explained.

Taking your methotrexate tablets

If you are taking methotrexate as tablets, always take them exactly as explained. This is important to make sure they work as well as possible. You should swallow the tablets whole with a full glass of water. Take them while sitting upright or standing.

If you are sick just after taking the tablets, contact the hospital. You may need to take another dose. If you forget to take a tablet, do not take a double dose. Keep to your regular schedule and let your doctor or nurse know.

Other things to remember about your tablets:

  • Keep them in the original package.
  • Store them at room temperature away from heat and direct sunlight.
  • Keep them safe and out of children’s reach.
  • If your treatment is stopped, return any remaining tablets to the pharmacist.

About side effects

We explain the most common side effects of this treatment here. We also include some less common side effects.

You may get some of the side effects we mention, but you are unlikely to get all of them. If you are also having treatment with other cancer drugs, you may have some side effects that we haven’t listed here. Always tell your doctor, nurse or pharmacist about any side effects you have.

Your doctor can give you drugs to help control some side effects. It is important to take them exactly as your nurse or pharmacist explains. This means they will be more likely to work for you. Your nurse will give you advice about managing your side effects. After your treatment is over, most side effects start to improve.

Serious and life-threatening side effects

Some cancer treatments can cause severe side effects. Rarely, these may be life-threatening. Your cancer doctor or nurse can explain the risk of these side effects to you.

Contact the hospital

Your nurse will give you telephone numbers for the hospital. If you feel unwell or need advice, you can call them at any time of the day or night. Save these numbers in your phone or keep them somewhere safe.

More information

We cannot list every side effect for this treatment. There are some rare side effects that are not listed. You can visit the electronic Medicines Compendium (eMC) for more detailed information.

Possible side effects of methotrexate

Risk of infection

This treatment can reduce the number of white blood cells in your blood. These cells fight infection. If the number of white blood cells is low, you are more likely to get an infection. A low white blood cell count is called neutropenia.

If you have an infection, it is important to treat it as soon as possible. Contact the hospital straight away on the 24-hour contact number you have if:

  • your temperature goes over 37.5°C (99.5F)
  • you suddenly feel unwell, even with a normal temperature
  • you have symptoms of an infection.

Symptoms of an infection include:

  • feeling shivery
  • a sore throat
  • a cough
  • diarrhoea
  • needing to pass urine often.

It is important to follow any specific advice your cancer treatment team gives you.

The number of white blood cells will usually return to normal before your next treatment. You will have a blood test before having more chemotherapy. If your white blood cell count is low, your doctor may delay your treatment for a short time.

Bruising and bleeding

Chemotherapy can reduce the number of platelets in your blood. Platelets are cells that help the blood to clot. Tell your doctor or nurse if you have any bruising or bleeding that you can’t explain. This includes:

  • nosebleeds
  • bleeding gums
  • tiny red or purple spots on the skin that may look like a rash.

Some people may need a drip to give them extra platelets. This is called a platelet transfusion.

Anaemia (low number of red blood cells)

Chemotherapy can reduce the number of red blood cells in your blood. These cells carry oxygen around the body. If the number of red blood cells is low, you may be tired and breathless. Tell your doctor or nurse if you feel like this. If you are very anaemic, you may need a drip to give you extra red blood cells. This is called a blood transfusion.

Feeling sick

You may feel sick in the first few days after chemotherapy. Your doctor will give you anti-sickness drugs to help prevent or control sickness. Take the drugs exactly as your nurse or pharmacist tells you. It is easier to prevent sickness than to treat it after it has started.

If you feel sick, take small sips of fluids and eat small amounts often. If you continue to feel sick, or if you vomit more than once in 24 hours, contact the hospital as soon as possible. They will give you advice and may change the anti-sickness drug to one that works better for you.

Loss of appetite

This treatment can affect your appetite. Do not worry if you don’t eat much for a day or two. But if your appetite does not come back after a few days, tell your nurse or dietitian. They will give you advice. They may give you food or drink supplements.


If you have diarrhoea, contact the hospital for advice. Try to drink at least two litres (three and a half pints) of fluids every day. It can help to avoid alcohol, caffeine, milk products, high-fat foods and high-fibre foods.

Feeling tired

Feeling tired is a common side effect. It is often worse towards the end of treatment and for some weeks after it has finished. Try to pace yourself and plan your day so you have time to rest. Gentle exercise, like short walks, can give you more energy. If you feel sleepy, do not drive or operate machinery.

Hair loss

Hair loss is rare with standard doses of methotrexate. If you are having high-dose treatment with methotrexate, all of the hair from your head will fall out. Your eyelashes, eyebrows and other body hair may also thin or fall out. This usually starts after your first or second cycle of chemotherapy. It is almost always temporary and your hair will grow back after chemotherapy ends. It is important to cover your scalp when you are out in the sun until your hair grows back. Your nurse can give you advice about coping with hair loss.

Scalp cooling is a way of lowering the temperature of the scalp to help reduce hair loss. Your nurse can tell you if this is an option for you.

Sore mouth

You may get a sore mouth or mouth ulcers. This can make you more likely to get a mouth infection. Use a soft toothbrush to clean your teeth or dentures in the morning, at night and after meals.

If your mouth is sore:

  • tell your nurse or doctor – they can give you a mouthwash or medicines to help
  • try to drink plenty of fluids
  • avoid alcohol, tobacco, and foods that irritate your mouth.

Skin changes

Methotrexate may affect your skin. Your doctor or nurse can tell you what to expect. If your skin feels dry, try using an unperfumed moisturising cream every day. During treatment, and for several months afterwards, you'll be more sensitive to the sun and your skin may burn more easily than usual. You can still go out in the sun, but use a suncream with a sun protection factor (SPF) of at least 30. You should also cover up with clothing and a hat. If you’ve had radiotherapy, the area that was treated may become red or sore.

Always tell your doctor or nurse about any skin changes. They can give you advice and may prescribe creams or medicines to help. Any changes to your skin are usually temporary and improve when treatment finishes.

Changes in the way the kidneys work

Methotrexate can affect how your kidneys work, but usually only when it’s given in high doses. You will have blood tests before and during treatment to check this. You will have extra fluids through a drip before and after chemotherapy. This is to protect your kidneys.

If there are any changes in how much urine you are producing, tell your nurse. You may be given sodium bicarbonate as a drip or as tablets during treatment. This is to reduce the risk of kidney problems. The nurses will also test your urine regularly.

Eye problems

Your eyes may become watery and feel sore. They may also become more sensitive to light. Your doctor can prescribe eye drops to help with this. If your eyes get red and inflamed (conjunctivitis), tell your doctor. This is because you may need antibiotic eye drops. Methotrexate may also cause blurry vision or eye pain. Always tell your doctor or nurse if you have eye pain or notice any change in your vision.

Muscle or joint pain

You may get pain in your muscles or joints for a few days after chemotherapy. If this happens, tell your doctor so they can give you painkillers. Tell them if the pain does not get better. Having warm baths and taking regular rests may help.

Tummy pain

You may get pain or discomfort in your tummy (abdomen), feel bloated or have indigestion or wind. Your doctor can prescribe drugs to help improve these symptoms. Tell them if the pain doesn’t improve, or if it gets worse.

Effects on the liver

This treatment can affect how your liver works. This is usually mild and goes back to normal after treatment. You will have blood tests to check how well your liver is working.


This treatment may cause headaches. If this happens, tell your doctor or nurse. They can give you painkillers.

Less common side effects of methotrexate

Effects on the nervous system

High doses of methotrexate can affect the nervous system. You may feel drowsy or confused. If you notice these symptoms, tell your doctor or nurse straight away. It is important not to drive or operate machinery if you notice these effects. Rarely, methotrexate can cause seizures (fits). You doctor or nurse will explain more about this.

Effects on the lungs

This treatment can cause changes to the lungs. Tell your doctor if you develop: 

  • a cough
  • wheezing
  • a fever (high temperature)
  • breathlessness.

You should also tell them if any existing breathing problems get worse. You may have tests to check your lungs.

Raised levels of uric acid in the blood

This treatment may cause the cancer/leukaemia cells to break down quickly. This releases uric acid (a waste product) into the blood. The kidneys usually get rid of uric acid but may not be able cope with large amounts. Too much uric acid can cause swelling and pain in the joints, which is called gout.

Your doctor may give you tablets called allopurinol (Zyloric®) to help prevent this. Drinking at least two litres of fluid a day will also help. You will have regular blood tests to check the uric acid levels.

Intrathecal chemotherapy

If you have intrathecal chemotherapy, the side effects you have may be different from the ones listed above. Intrathecal methotrexate can cause headaches, dizziness, tiredness, blurred vision and loss of balance for a few hours. If you have any of these effects, tell your doctor.

Other information about methotrexate

Blood clot risk

Cancer and some cancer treatments can increase the risk of a blood clot. Symptoms of a blood clot include:

  • pain, redness or swelling in a leg or arm
  • breathlessness
  • chest pain. 

If you have any of these symptoms, contact a doctor straight away. 

A blood clot is serious, but can be treated with drugs that thin the blood. Your doctor or nurse can give you more information.

Other medicines

Some medicines can affect chemotherapy or be harmful when you are having it. This includes medicines you can buy in a shop or chemist. Tell your cancer doctor about any drugs you are taking, including vitamins, herbal drugs and complementary therapies.


Your doctor will advise you not to drink alcohol while you're having methotrexate, as it can interact with the drug.


Some cancer drugs can affect whether you can get pregnant or father a child. If you are worried about this, it is important to talk with your doctor before you start treatment.


Your doctor will advise you not to get pregnant or father a child while having this treatment. The drugs may harm the developing baby. It is important to use effective contraception during your treatment.


If you have sex in the first few days after chemotherapy, you need to use a condom. This is to protect your partner in case there is any chemotherapy in semen or vaginal fluids.

Changes to your periods

Chemotherapy can sometimes stop the ovaries working. You may not get a period every month and they may eventually stop. In some women, this is temporary, but for others it is permanent and they start the menopause.


Women are advised not to breastfeed while having this treatment and for some time afterwards. This is because the drugs could be passed to the baby through breast milk.

Medical and dental treatment

If you need medical treatment for any reason other than cancer, always tell the doctors and nurses that you are having cancer treatment. Give them the contact details for your cancer doctor so they can ask for advice.

If you think you need dental treatment, talk to your cancer doctor or nurse. Always tell your dentist you are having cancer treatment.