Methotrexate is a chemotherapy drug that is given as a treatment for many types of cancer. This information should ideally be read with our general information about chemotherapy and your type of cancer.
What methotrexate looks like
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Methotrexate is a yellow fluid. It's also available as 2.5mg and 10mg yellow tablets.
Methotrexate may be given in one of the following ways:
as an injection through a fine tube (cannula) inserted into a vein (intravenously), usually in the back of your hand
through a fine, plastic tube inserted under the skin into and a vein near your collarbone (central line)
into a fine tube inserted into a vein in the crook of your arm (PICC line) as a drip (infusion) into the vein through a cannula or line.
Methotrexate can also be given:
by injection under the skin (subcutaneously)
by injection into a muscle (intramuscularly)
by injection into an artery (intra-arterially)
by injection into the fluid around the spinal cord through a lumbar puncture (intrathecally)
by injection through a device called an ommaya reservoir, that has been inserted into an area beneath the scalp (intraventricularly)
as tablets that you should swallow whole with plenty of water - it's important to take them as directed by your doctor.
Only certain specially-trained staff are able to give intrathecal methotrexate, so it may be given in a different part of your hospital and by different staff from the rest of your chemotherapy. In some situations, you may have to travel to a different hospital to have intrathecal methotrexate.
Chemotherapy is usually given as a course of several sessions (cycles) of treatment over a few months. The length of your treatment and the number of cycles you have will depend on the type of cancer you are being treated for. Your nurse or doctor will discuss your treatment plan with you.
Before you begin your treatment your doctor will arrange for you to have blood tests. You'll usually be given anti-sickness drugs before and/or during your treatment.
Each person’s reaction to chemotherapy is different. Some people have very few side effects while others may experience more. The side effects described below won't affect everyone who has methotrexate and may be different if you're having more than one type of chemotherapy drug.
We have outlined the most common side effects but haven't included those that are rare and unlikely to affect you. If you notice any side effects that aren't listed below, discuss them with your doctor, chemotherapy nurse or pharmacist.
Risk of infection
Methotrexate can reduce the number of white blood cells, which help fight infection. White cells blood are produced by the bone marrow. If the number of your white blood cells is low you will be more prone to infections. A low white blood cell count is called neutropenia.
Neutropenia can begin seven days after treatment, and your resistance to infection usually reaches its lowest point 10-14 days after chemotherapy. Your blood cells will then increase steadily and usually return to normal before your next cycle of chemotherapy is due.
Contact your doctor or the hospital straight away if:
your temperature goes above 38ºC (100.4ºF)
you suddenly feel unwell even with a normal temperature.
You'll have a blood test before having more chemotherapy to check the number of white cells in your blood. Occasionally, it may be necessary to delay your treatment if the number of blood cells (blood count) is still low.
If you're having methotrexate as a course of tablets, you may be given them every week for a number of weeks. Your blood cell count will be monitored throughout the course of treatment to make sure the number of your white blood cells does not get too low.
Bruising or bleeding
Methotrexate can reduce the production of platelets, which help the blood to clot. Tell your doctor if you have any unexplained bruising or bleeding, such as nosebleeds, bleeding gums, blood spots or rashes on the skin. You may need to have a platelet transfusion if your platelet count is low.If you have black or tarry stools let your doctor know straight away.
Methotrexate can reduce the number of red blood cells, which carry oxygen around the body. A low red blood cell count is called anaemia. This may make you feel tired and breathless. Tell your doctor or nurse if you have these symptoms. You may need to have a blood transfusion if the number of red blood cells becomes too low.
Your mouth may become sore or dry, or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help reduce the risk of this happening. Some people may find sucking on ice soothing. Tell your nurse or doctor if you have any of these problems, as they can prescribe mouthwashes and medicine to prevent or clear mouth infections.
You may notice that food tastes different. Normal taste usually comes back after treatment finishes. A dietitian or specialist nurse at your hospital can give you advice about ways of coping with this side effect. You may find our section about eating well helpful.
Methotrexate can cause diarrhoea. This can usually be easily controlled with medicine, but tell your doctor if it's severe or continues. It's important to drink plenty of fluids if you have diarrhoea.
Feeling tired is a common side effect of chemotherapy, especially towards the end of treatment and for some weeks after it’s over. It’s important to try to pace yourself and get as much rest as you need. Try to balance this with some gentle exercise, such as short walks, which will help. If tiredness is making you feel sleepy, don’t operate or drive machinery. You might like to read our section about ways of coping with fatigue.
Your skin may darken due to excess production of pigment. If it does, it usually goes back to normal a few months after the treatment has finished.
During treatment and for several months afterwards, you'll be more sensitive to the sun, and your skin may burn more easily than normal. You can still go out in the sun, but should wear a sun cream with a high sun protection factor (SPF) and cover up with clothing and a hat.
Your kidneys may be affected
Very high doses of methotrexate can damage the kidneys, but it’s rare for this to happen when standard doses are given. To prevent this you may be given sodium bicarbonate, either as tablets or capsules, or as an infusion into the vein, before and during the methotrexate treatment. You'll have a blood test before each methotrexate treatment to check your kidneys are working normally.
Methotrexate may cause an inflammation of the lining of the eyelids (conjunctiva) that makes your eyes feel sore, red and itchy (conjunctivitis). Let your doctor know if you develop eye problems as they can prescribe soothing eye drops if necessary.
Less common side effects
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Feeling sick (nausea) and being sick (vomiting)
Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent or greatly reduce nausea and vomiting. If the sickness isn't controlled, or if it continues tell your doctor; they can prescribe other anti-sickness drugs that may be more effective.
Some anti-sickness drugs can cause constipation. Let your doctor or nurse know if this is a problem.
Fever and chills
These may occur from the time your treatment is given, but they don’t usually last long. Your doctor may prescribe medicines to reduce these effects.
Pain in joints or muscles
You may have these symptoms a few days after treatment with methotrexate. This doesn't usually last long and your doctor can prescribe mild painkillers to help.
Methotrexate may affect your eyesight, however this is very rare. Let your doctor know if you notice any change in your vision.
This is very rare at low doses but often happens when high doses are given. Hair may become thinner or occasionally fall out completely. If this happens, it usually begins about 3-4 weeks after starting treatment, although it may occur earlier. You may also have thinning and loss of eyelashes, eyebrows and hair in other areas of the body.
This is temporary, and your hair will start to grow back once the treatment has finished. You may find that your hair grows back straighter, curlier, finer, or a slightly different colour than it was before treatment. Your nurse can give you advice about coping with hair loss.
Methotrexate can cause a rash or dry skin, which may be itchy.
Your doctor can prescribe medicine to help with this. Areas of skin that have previously been treated with radiotherapy may become red and sore. Let your doctor know if this happens.
Changes to the lungs
The chemotherapy may cause some changes to the lungs. Tell your doctor if you smoke or if you notice any coughing or breathlessness.
Your liver may be temporarily affected
Treatment with methotrexate may cause changes in the way your liver works, although it will return to normal when the treatment finishes. You're very unlikely to notice any problems, but your doctor will take regular blood samples to check your liver is working properly.
Signs of an allergic reaction include skin rashes and itching, a high temperature (fever), shivering, reddening of the face, dizziness, a headache, breathlessness, anxiety, and a feeling that you want to pass urine. You'll be monitored for any signs of an allergic reaction during the treatment.
It’s important to let your doctor know straight away if you feel unwell or have any severe side effects, even if they’re not mentioned here.
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When methotrexate is given in high doses into the fluid around the spinal cord, or into the brain, it 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.
A drug called folinic acid may be given 24 hours after starting methotrexate treatment to reduce the side effects. While you're attached to a drip, the folinic acid can be given into the vein (intravenously), otherwise it is given as tablets. It's very important you take the folinic acid on time and that you take all the tablets as directed by your doctor. It's often called ‘folinic acid rescue’ when given in this way after methotrexate treatment.
Conditions other than cancer
Methotrexate may be prescribed for conditions other than cancer. The drug dosage will be much lower, and so the side effects mentioned in this section will probably not occur. You should discuss the treatment and any possible side effects with your relevant specialist.
Risk of developing a blood clot
Cancer can increase the risk of developing a blood clot (thrombosis), and chemotherapy may increase this risk further.
A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious, so it’s important to tell your doctor straight away if you notice any of these symptoms. Most clots can be treated with drugs that thin the blood. The doctor or nurse can give you more information.
Some medicines, including those you can buy in a shop or chemist, can be harmful to take when you're having chemotherapy.
Tell your doctor about any medicines you're taking, including over-the-counter drugs, complementary therapies and herbal drugs.
Some painkillers, such as ibuprofen, can make the side effects of methotrexate worse. Before taking any painkillers, check with your chemotherapy nurse, pharmacist or doctor.
Methotrexate may interact with alcohol. It's advisable not to drink alcohol while you're having treatment.
Your ability to become pregnant or father a child may be affected by having this treatment. It's important to discuss fertility with your doctor before starting treatment.
It's not advisable to become pregnant or father a child while having methotrexate as it may harm the developing baby. It’s important to use effective contraception while having this drug and for at least a few months afterwards. You can discuss this with your doctor.
It’s not known whether chemotherapy drugs can be present in semen or vaginal fluids. To protect your partner, it’s safest to either avoid sex or use a barrier form of contraception for about 48 hours after chemotherapy.
There's a potential risk that chemotherapy drugs may be present in breast milk. Women are advised not to breastfeed during chemotherapy and for a few months afterwards.
It’s a good idea to know who you should contact if you have any problems or troublesome side effects when you’re at home. Your chemotherapy nurse or doctor will give you details of who to contact for advice. This should include ‘out-of hours’ contact details if you need to call someone at evenings, overnight or at the weekend.
If you’re admitted to hospital for a reason not related to the cancer, it’s important to tell the doctors and nurses looking after you that you're having chemotherapy treatment. You should tell them the name of your cancer specialist so that they can ask for advice.
Things to remember about methotrexate tablets
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Swallow your tablets whole with a glass of water.
It's important to take your tablets at the right times as directed by your doctor, nurse or pharmacist.
Always tell any doctors treating you for non-cancerous conditions that you're taking a course of chemotherapy tablets that shouldn't be stopped without the advice of your cancer specialist.
Keep the tablets in their original packaging and store them at room temperature away from heat and direct sunlight.
Keep your tablets in a safe place and out of the reach of children.
If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist. Don't flush them down the toilet or throw them away.
If you're sick just after taking the tablet tell your doctor as you may need to take another dose. Don't take another tablet without telling your doctor first.
If you forget to take a tablet, don't take a double dose. Inform your doctor and keep to your regular dose schedule.
This section is based on our methotrexate fact sheet, which has been compiled using information from a number of reliable sources, including:
Sweetman, et al. Martindale: The Complete Drug Reference. 37th edition. 2011. Pharmaceutical Press.
British National Formulary. 62nd edition. 2011. British Medical Association and Royal Pharmaceutical Society of Great Britain.
electronic Medicines Compendium (eMC). www.medicines.org.uk (accessed October 2011).