Methotrexate is a medicine that damps down the immune system. It is taken once a week only — as tablets or as an injection under the skin — and never every day.

Why you are taking it

It is used mainly in Crohn’s disease, to bring a flare under control, keep the disease settled and help you stop or avoid steroids — often when azathioprine or mercaptopurine has not suited you. It is also given at a lower dose alongside an anti-TNF medicine such as infliximab or adalimumab, to stop the body making antibodies against it, which helps the anti-TNF keep working. It is not usually used on its own in ulcerative colitis, because it did not work well enough in trials. It works slowly, and the trade-off is regular blood tests and avoiding alcohol completely.

How to take it

Take methotrexate once a week only, on the same day each week. Choose a day you will remember and write it on your calendar and your medicine box; taking it every day by mistake can cause a dangerous overdose. A common schedule in Crohn’s disease is 25 mg once a week as an injection for the first three to four months, then 15 mg once a week; alongside an anti-TNF a lower dose is often used. Injections are absorbed more reliably than tablets, especially at higher doses. Tablets come in more than one strength, so check every time that the strength and the number of tablets match your prescription; swallow them whole with water and wash your hands afterwards. You will also take folic acid, usually 5 mg once a week on the day after your methotrexate — never on the same day — to reduce side effects such as nausea and mouth ulcers. If you miss a dose and remember within two days, take it then; if more than two days have passed, contact your doctor for advice. Never take two doses together. Before the first dose we check your blood count and liver and kidney tests, check for hepatitis B and C, HIV, previous chickenpox and, if needed, tuberculosis, and sometimes arrange a chest X-ray. Women who could become pregnant have a pregnancy test before starting.

How long it takes to work

Methotrexate works slowly. Some people notice benefit after six to eight weeks, but the full effect can take three to four months, so we usually assess the response at about sixteen weeks. Keep taking it during this time, even if you do not yet feel a difference.

Blood tests and monitoring

We check your blood count and liver and kidney tests every two weeks after starting, until you have been on a steady dose for six weeks, then every month for three months, and then every three months for as long as you take it. The closer checks are repeated after any increase in dose. These tests pick up effects on the blood and liver before they cause harm, which is why methotrexate cannot be continued if they are missed.

Side effects

Important precautions

• Methotrexate is taken once a week only. Keep it apart from your daily medicines, and if you have taken more than prescribed, or taken it daily by mistake, go to the Emergency Department straight away.
• Avoid alcohol completely while you take methotrexate, as together they can damage the liver.
• Tell every doctor, dentist and pharmacist that you take methotrexate, and check before taking any new medicine, including those bought without a prescription. Never take trimethoprim or co-trimoxazole (Septrin, Bactrim), antibiotics often used for urine and chest infections: with methotrexate they can dangerously lower the blood count. Avoid anti-inflammatory painkillers such as ibuprofen, diclofenac and naproxen, which raise the methotrexate level and can trigger a flare; paracetamol is safe. Some other antibiotics, such as penicillins, can also raise the level.
• Do not take your dose if you have an active infection or a fever, or diarrhoea or vomiting that is making you dehydrated — contact your doctor first.
• No live vaccines (for example yellow fever, MMR, live chickenpox vaccine or BCG) during treatment; if one is needed it is given at least four weeks before you start, or at least three months after stopping. Non-live vaccines are recommended, including the shingles vaccine Shingrix — see sheets PE-IBD-04 and PE-IBD-18.
• Injections come as ready-filled pens or syringes. We will teach you to inject under the skin of the thigh or abdomen, changing the site each time; put used pens straight into the sharps bin. Store methotrexate below 25 °C, away from light and out of the reach of children — check the label. Anyone who is pregnant or planning a pregnancy should not handle the tablets or injections. Wash off any splash on the skin, or in the eyes, with plenty of water.
• Do not stop methotrexate yourself, even when you feel well. Tell your doctor if you have missed more than one dose or have run out.
• For a repeat prescription, message the clinic. If there is no reply after 48 hours send the message again, and if there is still no reply, come to the clinic.

Pregnancy and breastfeeding

Methotrexate can cause miscarriage and harm an unborn baby, so it must not be taken in pregnancy. Women who could become pregnant must use effective contraception during treatment and for at least six months after the last dose. Men taking methotrexate, or their partners, should use reliable contraception during treatment and for at least three months after the last dose, and men should not donate semen during this time. If you are planning a pregnancy, talk to your doctor well in advance so they can change your medicine. If you become pregnant, stop methotrexate and phone your doctor the same day — do not wait for a reply to a message. If your partner becomes pregnant while you are taking it, tell your doctor; the evidence for fathers taking low-dose methotrexate is reassuring. Do not breastfeed while taking methotrexate.

This leaflet is general information and does not replace advice from your own doctor.