Methotrexate is a chemotherapy drug used to treat many different cancers.
This information should ideally be read with our general information about chemotherapy and your type of cancer.
How methotrexate is given
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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 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 about how you have been. 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.
Your nurse will give you anti-sickness drugs and sometimes a steroid before you start. Methotrexate is then given in one of the following ways:
through a short thin tube (cannula) that the nurse puts into a vein in your arm or hand
through a fine tube that goes under the skin of your chest and into a vein close by (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)
by injection into the fluid around the spinal cord (intrathecally)
rarely by injection into an artery (inter-arterial injection).
When the chemotherapy is being given
Some people might have side effects while they are having the chemotherapy.
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. Tell the nurse straight away if you have any stinging, pain, redness or swelling around the vein. Extravasation is not common but if it happens it’s important that it’s dealt with quickly.
If you get any of these symptoms after you get home, contact the doctor or nurse straight away on the number they gave you.
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's 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 the reach of children.
Return any remaining tablets to the pharmacist if your treatment is stopped.
Chemotherapy 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. 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 need to lie flat for a few hours afterwards and drink plenty of fluids.
Your course of methotrexate
You have chemotherapy as a course of several sessions (or cycles) of treatment over a few months. Your doctor or nurse will tell you the number of cycles you are likely to have.
Possible side effects of methotrexate
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We explain the most common side effects of methotrexate here. But we don’t include all the rare ones that are unlikely to affect you.
You may get some of the side effects we mention, but you are very unlikely to get all of them. If you are having other chemotherapy drugs as well, you may have some side effects that we don’t list here. Always tell your doctor or nurse about the side effects you have.
Your doctor can prescribe drugs to help control some side effects. It is very important to take them exactly as your nurse or pharmacist has explained. This means they will be more likely to work better for you. Your nurse will give you advice about managing your side effects. After your treatment is over, the side effects will start to improve.
Contact the hospital
Your nurse will give you telephone numbers for the hospital. You can call them if you feel unwell or need advice any time of day or night. Save these numbers in your phone or keep them somewhere safe.
Risk of infection
Chemotherapy can reduce the number of white blood cells in your blood. This will make you more likely to get an infection. When the number of white blood cells is low, it’s called neutropenia.
Contact the hospital straight away on the contact number you’ve been given if:
your temperature goes over 37.5°C (99.5°F) or over 38°C (100.4°F), depending on the advice given by your chemotherapy team
you suddenly feel unwell, even with a normal temperature
you have symptoms of an infection – this can include feeling shaky, a sore throat, a cough, diarrhoea or needing to pass urine a lot.
The number of white blood cells usually increases steadily and returns to normal before your next treatment. You will have a blood test before having more chemotherapy. If your white blood cells are still low, your doctor may delay your treatment for a short time.
Bruising and bleeding
Methotrexate 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 you can’t explain. This includes nosebleeds, bleeding gums, blood spots or rashes on the skin. Some people may need a drip to give them extra platelets.
Anaemia (low number of red blood cells)
Methotrexate 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 (blood transfusion).
This may happen in the first few days after chemotherapy. Your doctor will prescribe anti-sickness (anti-emetic) drugs to help prevent or control sickness. Take the drugs exactly as your nurse or pharmacist explains to you. It’s easier to prevent sickness than to treat it after it has started.
If you still feel sick or are vomiting, contact the hospital as soon as possible. They can give you advice and change the anti-sickness drug to one that works better for you. Some anti-sickness drugs can make you constipated. Tell your doctor or nurse if this is a problem.
Loss of appetite
You may lose your appetite during your treatment. Try to eat small meals regularly. Don’t worry if you don’t eat much for a day or two. If your appetite doesn’t improve after a few days, let your nurse or dietitian know. They can give you advice on getting more calories and protein in your diet. They may give you food supplements or meal replacement drinks to try. Your doctor can prescribe some of these and you can buy them from chemists.
Your doctor can prescribe drugs to control diarrhoea. Let them know if it is severe or if it doesn’t get better. Make sure you drink at least two litres (three and a half pints) of fluids every day if you have diarrhoea.
Feeling very tired is a common side effect. It’s often worse towards the end of treatment and for some weeks after. Try to pace yourself and get as much rest as you need. It helps to balance this with taking some gentle exercise, such as short walks. If you feel sleepy, don’t drive or operate machinery.
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.
Your mouth may become sore and you may get ulcers. This can make you more likely to get an infection in your mouth. Gently clean your teeth and/or dentures morning and night and after meals. Use a soft-bristled or children’s toothbrush. Your nurse might ask you to rinse your mouth regularly or use mouthwashes. It’s important to follow any advice you are given and to drink plenty of fluids.
Tell your nurse or doctor if you have any problems with your mouth. They can prescribe medicines to prevent or treat mouth infections and reduce any soreness.
Chemotherapy 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, and 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 only usually when it’s given in high doses. You will have blood tests before and during treatment to check this. You’ll have extra fluids through a drip before and after chemotherapy. This is to protect your kidneys.
Tell your nurse if there are any changes in how much urine you are producing. 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.
Your eyes may become watery and feel sore and may 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 and joint pain
You may get pain in your joints or muscles for a few days after chemotherapy. Tell your doctor if this happens so they can prescribe painkillers. Let them know if the pain does not get better. Try to get plenty of rest. Taking regular warm baths may help.
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 gets worse.
Changes in the way the liver works
Methotrexate may 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.
Methotrexate may cause headaches. If this happens, let your doctor or nurse know. They can give you painkillers.
Less common side effects of methotrexate
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Effects on the nervous system
High doses of methotrexate can affect the nervous system. You may feel drowsy or confused. Tell your doctor or nurse straight away if you notice any of these symptoms. It’s 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
Methotrexate can cause changes to the lungs. Always tell your doctor if you develop wheezing, a cough, a fever or feel breathless. You should also let them know if any existing breathing problems get worse. If necessary, they can arrange for you to have tests to check your lungs.
If you have intrathecal chemotherapy, the side effects you have may be different from those mentioned already. Intrathecal methotrexate can cause headaches, dizziness, tiredness, blurred vision and loss of balance for a few hours. Tell your doctor if you have any of these effects.
Other information about methotrexate
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Blood clot risk
Cancer increases the chance of a blood clot (thrombosis) and chemotherapy can add to this. A clot can cause symptoms such as pain, redness and swelling in a leg, breathlessness and chest pain. Contact your doctor straight away if you have any of these symptoms. A blood clot is serious but your doctor can treat it with drugs that thin the blood. Your doctor or nurse can give you more information.
Some medicines can interact with chemotherapy or be harmful when you are having chemotherapy. This includes ones you can buy in a shop or chemist. Tell your doctor about any medicines you are taking, including over-the-counter drugs, complementary therapies and herbal drugs. Some medicines such as ibuprofen and aspirin can make the side effects of methotrexate worse. Before taking any medicines, check with your pharmacist, nurse or doctor.
Your doctor will advise you not to drink alcohol while you're having methotrexate, as it can interact with the drug.
Methotrexate may affect your fertility (being able to get pregnant or father a child). If you are worried about this, you can talk to your doctor or nurse before treatment starts.
Your doctor will advise you not to become pregnant or to father a child during treatment. This is because the drugs may harm a developing baby. It’s important to use effective contraception during and for a few months after chemotherapy. You can talk to your doctor or nurse about this.
If you have sex within the first couple of days of having chemotherapy, you need to use a condom. This is to protect your partner in case there is any chemotherapy in semen or vaginal fluid.
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 during treatment and for a few months after. This is in case there is chemotherapy in their breast milk.
Medical and dental treatment
If you need to go into hospital for any reason other than cancer, always tell the doctors and nurses that you are having chemotherapy. Explain you are taking chemotherapy tablets that no one should stop or restart without advice from your cancer doctor. Give them contact details for your cancer doctor.
Talk to your cancer doctor or nurse if you think you need dental treatment. Always tell your dentist you are having chemotherapy.
This section has been compiled using information from a number of reliable sources including:
electronic Medicines Compendium (eMC). medicines.org.uk (accessed July 2013).
Perry MC. The Chemotherapy Source Book. 5th edition. 2012. Lippincott Williams and Wilkins.
With thanks to Elin Gwyn, Macmillan Pharmacist, who reviewed this edition.
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