What is methotrexate?

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.

Your doctor will talk to you about this treatment and its possible side effects before you agree (consent) to have treatment.

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.

Sometimes, methotrexate is given as tablets or a liquid at home. 

Methotrexate can be given in combination with other cancer drugs. 

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

You will have regular blood tests during treatment. A nurse or person trained to take blood (phlebotomist) will take a blood sample from you. This is to check that your blood cells are at a safe level to have chemotherapy. 

You will see a doctor or nurse before you have chemotherapy. They will talk to you about your blood results and ask you how you have been feeling. If your blood results are okay, the pharmacist will prepare your chemotherapy. Your nurse will tell you when your treatment is likely to be ready.

Your nurse usually gives you anti-sickness (anti-emetic) drugs before the chemotherapy. 

If you will be taking methotrexate as tablets or a liquid at home, your nurse or pharmacist will give you anti-sickness (anti-emetic) drugs and other medicines to take with you. Take all your tablets exactly as they have been explained to you.

You may have the chemotherapy drugs through: 

  • a cannula – a short, thin tube the nurse puts into a vein in your arm or hand
  • a central line – a fine tube that goes under the skin of your chest and ito a vein close by
  • a PICC line – a fine tube that is put into a vein in your arm and goes up into a vein in your chest
  • an implantable port (portacath) – a disc that is put under the skin on your chest or arm and goes into a vein in your chest.

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 usually have fluids through the drip at the same time.

Methotrexate can also be given:

  • as tablets or a liquid to swallow 
  • by injection into the fluid around the spinal cord (intrathecal chemotherapy)
  • as an injection into a muscle (intramuscular injection)
  • by injection into an artery (inter-arterial injection), but this is rare.

Folinic acid rescue

A drug called folinic acid (also called leucovorin or calcium folinate) is sometimes given after methotrexate. It is mainly used with higher doses of methotrexate to help reduce the side effects. This is sometimes called folinic acid rescue or leucovorin rescue.

Folinic acid can be given into your cannula or line. You have it regularly through a drip until the methotrexate is out of your system. You will have fluids through the drip at the same time.

Folinic acid is sometimes given as tablets. It is very important to take the tablets exactly as explained.

Taking your methotrexate tablets or liquid

If you are taking methotrexate as tablets or a liquid, always take it exactly as explained. This is important to make sure the treatment works as well as possible.

You should swallow the tablets whole with a full glass of water. They should not be chewed, broken or crushed. 

If you have the liquid, measure out the dose carefully. Drink a glass of water after the methotrexate to rinse your mouth.

If you are sick just after taking methotrexate, contact the hospital for advice. Do not take another dose. If you forget to take methotrexate, do not take a double dose. Keep to your regular schedule and let your doctor or nurse know.

Other things to remember about this drug are:

  • wash your hands after taking your tablets or liquid
  • other people should avoid direct contact with the chemotherapy drugs
  • keep it in the original package and at room temperature, away from heat and direct sunlight
  • keep it safe and out of sight and reach of children
  • if your treatment is stopped, return any unused drug to the pharmacist.

Lactose

Methotrexate tablets contain a small amount of lactose. If you have a lactose intolerance, talk to your doctor before taking methotrexate tablets.

Methotrexate by injection into the spinal fluid

In some cancers, such as some types of leukaemia or lymphoma, cancer cells can pass into the cerebrospinal fluid (CSF). You may be given intrathecal chemotherapy if a cancer has spread to the CSF, or there is a risk it could.

Only certain chemotherapy drugs, including methotrexate, can be given in this way. You will have a lumbar puncture if you need to have methotrexate by injection into the spinal fluid.
You need to lie flat for at least 30 minutes after the lumbar puncture. Your doctor or nurse will tell you how long you should stay like this for. They will check your blood pressure and pulse during this time.

A lumbar puncture is usually a very safe procedure. But you may have a headache for a few days afterwards. If this happens, tell your doctor. They can give you painkillers to help. Drinking plenty of fluids (3 litres a day) for 2 days afterwards can help to reduce headaches.

Your course of chemotherapy

You usually have a course of several cycles of treatment over a few months. Your doctor, nurse or pharmacist will discuss your treatment plan with you.

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 have not listed here.

You may have some rarer side effects that we have not listed here. Always tell your doctor, nurse or pharmacist about any side effects you have.

Your doctor, nurse or pharmacist can give you drugs to help control some side effects. It is important to take them exactly as they tell you. This means the drugs will be more likely to work for you. Your doctor, nurse or pharmacist 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.

Side effects while methotrexate is being given

Some people may have side effects while they are being given the chemotherapy or shortly after they have it:

Allergic reaction

Some people have an allergic reaction while having this treatment. Signs of a reaction can include:

  • feeling hot or flushed
  • shivering
  • itching
  • a skin rash
  • feeling dizzy
  • a headache
  • feeling breathless or wheezy
  • swelling of your face or mouth
  • pain in your back, tummy or chest.

Your nurse will check you for signs of a reaction during your treatment. If you feel unwell or have any of these signs, tell them straight away. If you do have a reaction, it can be treated quickly.

Sometimes a reaction happens a few hours after treatment. If you develop any signs or feel unwell after you get home, contact the hospital straight away.

The drug leaks outside the vein

The drug may leak outside the vein. If this happens it can damage the tissue around the vein. This is called extravasation. Extravasation is not common but if it happens it is important that it is treated quickly. Tell your nurse straight away if you have any stinging, pain, redness or swelling around the vein.

Common side effects

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 sometimes called neutropenia.

An infection can be very serious when the number of white blood cells is low. It is important to get any infection treated as soon as possible. Contact the hospital straight away on the 24-hour contact number you have been given if:

  • your temperature goes over 37.5°C (99.5°F) 
  • you suddenly feel unwell, even with a normal temperature
  • you have symptoms of an infection
  • your temperature goes below 36°C (96.8°F). 

Symptoms of an infection include:

  • feeling shivery and shaking
  • a sore throat
  • a cough 
  • breathlessness
  • diarrhoea
  • needing to pass urine (pee) a lot, or discomfort when you pass urine.

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 regular blood tests during treatment. If needed, your doctor may reduce or delay your treatment for a short time, until your cell count increases.

Bruising and bleeding

This treatment can reduce the number of platelets in your blood. Platelets are cells that help the blood to clot.

If the number of platelets is low, you may bruise or bleed easily. You may have:

  • nosebleeds
  • bleeding gums
  • heavy periods
  • blood in your urine (pee) or stools (poo)
  • tiny red or purple spots on the skin that may look like a rash.

Tell your doctor if you have any unexplained bruising or bleeding. You may need a drip to give you extra platelets. This is called a platelet transfusion.

Anaemia (low number of red blood cells)

This treatment can reduce the number of red blood cells in your blood. Red blood cells carry oxygen around the body. If the number of red blood cells is low, this is called anaemia. You may have symptoms such as:

  • pale skin
  • lack of energy
  • feeling breathless
  • feeling dizzy and light-headed.

Tell your doctor or nurse if you have these symptoms.

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 will be given anti-sickness drugs to help prevent or control sickness during your treatment. If you feel sick or are sick (vomit), tell your nurse or doctor. They may change the anti-sickness drug to one that works better for you.

Loss of appetite

This treatment can affect your appetite. Don't worry if you do not eat much for a day or 2. But if your appetite does not come back after a few days, or if you are losing weight, tell your nurse or dietitian. They can give you advice. They may give you food or drink supplements. Or they may suggest changes to your diet or eating habits to help.

Sore mouth and throat

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

If your mouth or throat 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 and throat.

Sucking ice chips may sometimes help relieve mouth or throat pain. But if you are having radiotherapy to the head or neck, do not suck on ice. It can cause damage.

Diarrhoea

This treatment may cause severe diarrhoea. Diarrhoea means passing more stools (poo) than is usual for you, or having watery or loose stools. If you have a stoma, it will be more active than usual.

Your hospital team may give you anti-diarrhoea drugs to take at home.

If you have diarrhoea or a mild increase in stoma activity:

  • follow any advice from your cancer team about taking anti-diarrhoea drugs
  • drink at least 2 litres (3½ pints) of fluids each day
  • avoid alcohol, caffeine, milk products, high-fat foods and high-fibre foods.

Contact the hospital straight away if:

  • you have diarrhoea at night
  • you have diarrhoea more than 4 times in a day
  • you have a moderate or severe increase in stoma activity
  • the anti-diarrhoea drugs do not work within 24 hours.

You may need to go to hospital to have fluids through a drip.

Tummy pain

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

Skin changes

This treatment may cause skin changes, including:

  • a rash
  • itching
  • dry skin
  • patches of white or paler skin.

During treatment and for several months afterwards, you may be more sensitive to the sun. Your skin may burn more easily than usual. You can still go out in the sun, but use a sun cream with a sun protection factor (SPF) of at least 30, and cover up with clothing and a hat.

If you notice any skin changes during treatment or after it finishes, always tell your doctor or nurse straight away. You may need creams, steroids or other medicines. Your doctor may stop your treatment until the skin changes improve.

Rarely, a much more serious skin condition can develop. You may have:

  • a skin rash which then blisters
  • peeling skin
  • flu-like symptoms, such as a high temperature and joint pain.

If you have any of these symptoms, contact your doctor or hospital straight away.

Hair loss

Hair loss is rare with standard doses of methotrexate. If you are having high-dose treatment with methotrexate, you usually lose all the hair from your head. You may also lose your eyelashes and eyebrows, as well as other body hair.

Scalp cooling is a way of lowering the temperature of your scalp to help reduce hair loss. Your nurse can tell you if this is an option for you.
Hair loss is almost always temporary. Your hair will usually grow back after treatment finishes.

Effects on the kidneys

Methotrexate can affect how your kidneys work, but usually only when it is given in high doses. This will go back to normal when your treatment finishes. You will have blood tests to check how well your kidneys are working. Tell your doctor or nurse if you have blood in your urine (pee) or you are passing urine less than usual.

It is important to drink at least 2 litres (3½ pints) of non-alcoholic fluid each day to help protect your kidneys. 

Effects on the liver

This treatment may affect how your liver works. This is usually mild. You will have blood tests to check how well your liver is working.

Effects on the nervous system

High doses of this treatment can affect the nervous system. You may:

  • have headaches
  • feel dizzy
  • 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, this treatment can cause seizures (fits). Your doctor or nurse will explain more about this.

Eye problems

This treatment may make your eyes feel sore, red and itchy (conjunctivitis). Your doctor will usually prescribe eye drops to help with this. It is important to use these exactly as you are told to.

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.

Feeling tired

Feeling tired is a common side effect of this treatment. 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 use machinery.

Muscle or joint pain

You may get pain in your muscles or joints for a few days after treatment. 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.

Less common side effects of methotrexate

Effects on the lungs

This treatment can cause changes to the lungs. Contact the hospital straight away if you notice any of these changes during treatment or after it finishes:

  • breathlessness
  • a cough
  • wheezing
  • a fever, with a temperature over 37.5°C (99.5°F).

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

Tumour lysis syndrome (TLS)

This treatment may cause cancer cells to die and break down quickly. When cancer cells break down very quickly, it can cause a sudden release of large amounts of chemicals into the blood. This is called tumour lysis syndrome (TLS).

Your kidneys can usually keep these chemicals balanced. But they might not be able to cope with very large amounts. The chemical imbalance can affect how well your kidneys work and cause problems with your heart rhythm.

You will have regular blood tests to check the levels of these chemicals.

If you are at risk of TLS, your doctor can give you treatment to help prevent it. You may have:

  • extra fluids through a drip
  • medicines such as rasburicase or allopurinol.

Drinking at least 2 litres (3½ pints) of fluid a day will also help.

Hepatitis B reactivation

If you have had Hepatitis B (a liver infection) in the past, this treatment can make it active again. Your doctor or nurse will talk to you about this and may test you for Hepatitis B before, during, and after treatment.

Second cancer

This treatment can increase the risk of developing lymphoma. This is rare. The benefits of treatment usually far outweigh this risk. Your doctor can talk to you about this.

Side effects of 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
  • loss of balance.

These side effects can last for a few hours. If you have any of these, tell your doctor.

Other information

Blood clot risk

Cancer and some cancer treatments can increase the risk of a blood clot. Contact the hospital straight away on the 24-hour number if you have any of these symptoms during or after treatment:

  • throbbing pain or swelling in a leg or arm
  • reddening of the skin in the area – if you have black or brown skin, this can be harder to notice, but the skin might become darker
  • suddenly feeling breathless or coughing.

Always call 999 if you have:

  • chest pain
  • difficulty breathing.

A blood clot is serious, but it can be treated with drugs called anticoagulants. These thin the blood. Your doctor, nurse or pharmacist can give you more information about preventing and treating blood clots.

Other medicines

Some medicines can affect how this treatment works or be harmful while you are having it. Always tell your cancer doctor, nurse or pharmacist about any drugs you are taking or planning to take, such as: 

Alcohol

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

Changes to periods

If you have a period, these may become irregular or stop while you are having this treatment. This may be temporary, but it can sometimes be permanent. Your menopause may start sooner than it would have done. Your doctor or nurse can give you more information.

Fertility

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

Contraception

Your doctor will advise you not to get pregnant or make someone pregnant while having this treatment. The drugs may harm a developing baby. It is important to use contraception during your treatment and for a while after treatment finishes. Your doctor, nurse or pharmacist can tell you more about this.

Sex

If you have sex in the first few days after this treatment, you should use barrier protection such as a condom or dental dam. This will protect your partner if any of the drug is in your semen or vaginal fluids.

Breastfeeding

You are advised not to breastfeed while having this treatment, or for some time after treatment finishes. This is because the drugs could be passed to the baby through breast milk.

Your doctor or nurse can give you more information.

Medical and dental treatment

If you need medical treatment for any reason other than cancer, always tell the doctors and nurses 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.

About our information

  • Reviewers

    This information has been written, revised and edited by Macmillan Cancer Support’s Cancer Information Development team. It has been reviewed by expert health professionals and people living with cancer.

    Our cancer information has been awarded the PIF TICK. Created by the Patient Information Forum, this quality mark shows we meet PIF’s 10 criteria for trustworthy health information.

Date reviewed

Reviewed: 01 January 2023
|
Next review: 01 January 2025
Trusted Information Creator - Patient Information Forum
Trusted Information Creator - Patient Information Forum

Our cancer information meets the PIF TICK quality mark.

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