Methotrexate is a chemotherapy drug used to treat many different cancers.
Your doctor will talk to you about this treatment and its possible side effects before you agree (consent) to have treatment.
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.
Your nurse usually gives you anti-sickness (anti-emetic) drugs before the chemotherapy. You may also be given a steroid.
The chemotherapy drugs can be given through:
- a short, thin tube that the nurse puts into a vein in your arm or hand (cannula)
- a fine tube that goes under the skin of your chest and into a nearby vein (central line)
- 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 the 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:
- Wash your hands after taking your tablets and capsules.
- 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.
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.
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. 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.
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.
Some people have an allergic reaction while having this treatment. Signs of a reaction can include:
- feeling hot or flushed
- 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 surrounding tissue. This is called extravasation. Extravasation is not common but if it happens it is important to treat it quickly. Tell your nurse straight away if you have any stinging, pain, redness or swelling around the vein.
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
- 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 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, 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:
- 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.
The nurses will give you anti-sickness drugs regularly 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. 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.
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.
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.
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. 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 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.
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.
Sensitivity to the sun
During treatment and for several months afterwards, you will be more sensitive to the sun. Your skin may burn more easily than usual.
If you are going out in the sun, here are some tips for protecting yourself:
- Wear a wide-brimmed hat.
- Use a sun cream with a high sun protection factor (at least SPF 30).
- Wear clothing made of cotton or natural fibres.
- Avoid the sun between 11am and 3pm.
Changes in the way the kidneys work
This treatment 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.
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 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.
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 gets worse.
Effects on the liver
This treatment 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.
This treatment may cause headaches. If you have headaches, tell your doctor. They may give you painkillers to help.
Effects on the nervous system
Effects on the lungs
This treatment can cause changes to the lungs. Tell your doctor if you develop:
- a cough
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 (tumour lysis syndrome)
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 to 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 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.
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:
- blurred vision
- loss of balance.
These side effects can last for a few hours. If you have any of these, tell your doctor.
Blood clot risk
Cancer and some cancer treatments can increase the risk of a blood clot. Symptoms of a blood clot include:
- throbbing pain, redness or swelling in a leg or arm
- suddenly feeling breathless or coughing
- sharp chest pain, which may be worse when you cough or take a deep breath.
If you have any of these symptoms, contact the hospital straight away on the 24-hour contact number you have been given. If you cannot get through to your doctor, call the NHS urgent advice number on 111.
A blood clot is serious, but it can be treated with drugs that thin the blood (anticoagulants). Your doctor or nurse can give you more information.
You can help reduce the risk of developing a blood clot by:
- staying active during treatment
- drinking plenty of fluids, especially water.
You may be given anticoagulants to help prevent a clot.
Some medicines can affect how this treatment works or be harmful when you are having it. Always tell your cancer doctor about any drugs you are taking or planning to take, such as:
- medicines you have been prescribed
- medicines you buy in a shop or chemist
- vitamins, herbal drugs and complementary therapies.
Tell other doctors, pharmacists or dentists who prescribe or give you medicines that you are having this cancer treatment.
You can visit the electronic Medicines Compendium (eMC) for more detailed information about your treatment.
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.
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.
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.
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.