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.

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.

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.

Chemotherapy

This video provides a brief overview of chemotherapy treatment, how it can be given, how it works and possible side effects.

About our cancer information videos

Chemotherapy

This video provides a brief overview of chemotherapy treatment, how it can be given, how it works and possible side effects.

About our cancer information videos


How methotrexate is given

You can have methotrexate in the chemotherapy day unit or during a stay in hospital. A chemotherapy nurse will give it to you. Sometimes methotrexate can be taken as tablets or a liquid at home. Methotrexate can be given in combination with other 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.

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 your blood cells are at a safe level 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 okay, 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 can be given into a vein 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 can also be given:

  • as tablets or a liquid (oral drug)
  • 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 (leucovorin or calcium folinate) can be given after methotrexate treatment. This is to reduce the side effects. Folinic acid can be given into your cannula or line. You have it regularly with fluids through a drip 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

Methotrexate by injection into the spinal fluid

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

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.

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. Take them while sitting upright or standing. If you have the liquid, measure out the dose carefully. Have a glass of water after the methotrexate to rinse your mouth.

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

Other things to remember about your drug:

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

Your course of chemotherapy

You usually have a course of several cycles of treatment over a few months. Your nurse or doctor will discuss your treatment plan with you. This will depend on the type of cancer you have.

PICC lines and central lines playlist

Watch our short animated videos about having PICC lines and central lines put in.

PICC lines and central lines playlist

Watch our short animated videos about having PICC lines and central lines put in.


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.

Tips for talking to your doctor

Find out how to get the most out of your appointments with a GP or doctor.

About our cancer information videos

Tips for talking to your doctor

Find out how to get the most out of your appointments with a GP or doctor.

About our cancer information videos


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 
  • a skin rash
  • itching
  • shivering
  • feeling dizzy
  • a headache
  • feeling breathless 
  • 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 can happen a few hours after treatment. If you get any signs or feel unwell after you get home, contact the hospital straight away.

The drug leaks 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 dealt with quickly. Tell your nurse straight away if you have any stinging, pain, redness or swelling around the vein.

If you get any of these symptoms after you get home, contact the doctor or nurse straight away. You should use the number they gave you.


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 (99.5°F)
  • 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 treatment. If your white blood cell count is low, your doctor may delay your treatment for a short time.

Bruising and bleeding

This treatment can reduce the number of platelets in your blood. Platelets are cells that help the blood to clot. Tell your doctor if you have any bruising or bleeding that you cannot 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)

This treatment 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 of your chemotherapy. The nurses will give you anti-sickness drugs regularly. If you still feel sick, tell your nurse or doctor. They can 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 do not 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.

Diarrhoea

This treatment may cause severe diarrhoea. Your nurse or doctor may give you anti-diarrhoea drugs to take at home.

If you have diarrhoea:

  • follow any advice you have been given 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 6 times in a day
  • the anti-diarrhoea drugs do not work within 24 hours.

Some people may need to go to hospital to have fluids through a drip. You may need to take antibiotics.

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, eye-brows and other body hair may also thin or fall out. Hair loss is usually temporary, and your hair will usually grow back after treatment ends. 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.

Always tell your doctor or nurse about any skin changes such as a rash or itch. 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.

Very rarely, a much more serious skin condition can occur. You may have a skin rash which then blisters and your skin can peel. You may also feel unwell with flu-like symptoms such as a high temperature and joint pain. If you have these symptoms, you must stop taking the methotrexate and contact your doctors immediately.

Sun sensitivity

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

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. Before and after each treatment, your nurses will give you extra fluids through a drip. This is to protect your kidneys. It is also important to drink at least 2 litres (3½ pints) of fluids each day.

If you pass less urine (pee) than usual, tell your nurse.

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.

Headaches

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

A photo of Stuart talking about neutropenic sepsis

Neutropenic sepsis

Stuart talks about he how coped with neutropenic sepsis, an infection which can be a side effect of chemotherapy.

About our cancer information videos

Neutropenic sepsis

Stuart talks about he how coped with neutropenic sepsis, an infection which can be a side effect of chemotherapy.

About our cancer information videos

Coping with fatigue

Denton describes how he coped with fatigue (tiredness) during his treatment for prostate cancer.

About our cancer information videos

Coping with fatigue

Denton describes how he coped with fatigue (tiredness) during his treatment for prostate cancer.

About our cancer information videos


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 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 (gout).

Your doctor may give you drugs to help prevent this. Drinking at least 2 litres (3½ pints) 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
  • loss of balance

These side effects can last for a few hours. If you have any of these, 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 over-the-counter drugs, complementary therapies and herbal drugs.

Alcohol

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

Fertility

Some chemotherapy drugs can affect whether you can get pregnant or father a child.

If you are a woman, your periods may become irregular or stop. This may be temporary, but for some women it is permanent. Your menopause may start sooner than it would have done.

There may be ways to preserve fertility for men and women. If you are worried about fertility, it is important to talk with your doctor before you start chemotherapy treatment.

Contraception

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.

Sex

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.

Breastfeeding

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.