Methotrexate

Methotrexate is the most widely used disease-modifying anti-rheumatic drug (DMARD) in rheumatology, and for most people with rheumatoid arthritis it is the first treatment offered. It is also used in psoriatic arthritis, in juvenile idiopathic arthritis continuing into adult life, and in a range of other inflammatory conditions, including some forms of vasculitis and connective tissue disease. If rheumatology has an anchor medicine, this is it.

It earns that place by treating the disease rather than just the symptoms. Inflammatory arthritis is driven by an overactive immune system, and methotrexate calms that overactivity: it eases pain and swelling and, more importantly, protects the joints from the damage that uncontrolled inflammation causes over time. It is not a painkiller, and it works slowly. Most people begin to notice benefit after several weeks, and the full effect can take two to three months, so a steroid is sometimes used as a bridge while it takes hold. How methotrexate sits alongside the other medicines in its family is covered in our guide to DMARDs in rheumatology, and the options if it is not enough on its own in biologics and JAK inhibitors.

This is one of the most common worries about methotrexate, and it deserves a straight answer. Methotrexate is the same molecule that is used, at doses many times higher, to treat some cancers, and the printed leaflet in the box describes those uses, which alarms many people at the very start of treatment. In rheumatology it is used entirely differently: a small dose, once a week, with the aim of calming immune overactivity rather than destroying cells. At these low weekly doses it does not behave like chemotherapy and is not experienced like chemotherapy, and the effects people associate with cancer treatment are not what methotrexate treatment is like. What it shares with its higher-dose relative is the name, not the experience.

Methotrexate is taken once a week, on the same day each week. It must never be taken daily. Most regular medicines are daily, which is exactly why this rule is stated so firmly everywhere methotrexate is prescribed: taking it every day by mistake is dangerous. Choose a fixed day, build a routine around it, and if you are ever unsure whether you have taken a dose, or think an extra one may have been taken, do not guess and do not double up: contact your prescribing team, a pharmacist or NHS 111 for advice.

Folic acid, a vitamin, is usually prescribed alongside methotrexate. Its job is to reduce side effects such as nausea and mouth ulcers without blunting the benefit, and your prescriber will set out how and when to take it as part of the same weekly routine.

Methotrexate comes as tablets and as a once-weekly injection under the skin from a pre-filled pen, which most people quickly learn to give themselves. Tablets are the usual starting point. The injection is a useful alternative when tablets cause nausea or when the response to them is incomplete, because the injected form reaches the body more reliably. Whichever form you use, the once-a-week rule is the same.

Most people take methotrexate with few problems, but side effects are common in the early months and it is honest to say so. Nausea, or a washed-out, fragile feeling on the day after the dose, is the one people mention most; tiredness, mouth ulcers, mild headaches and slight thinning of the hair also occur. These often ease as the body adjusts and the folic acid does its work. If they persist, there is usually something that can be done: the timing, the folic acid arrangements and the form of methotrexate can all be adjusted, and a switch from tablets to the injection settles nausea for many. Those adjustments are your prescriber's to make, so raise them at a review rather than changing anything yourself.

The rare but serious side effects are the reason methotrexate is supervised, and knowing them makes you safer, not more anxious. Rarely, and usually in the first months of treatment, methotrexate can trigger an allergic-type inflammation of the lungs called pneumonitis, which typically settles once the medicine is stopped, so a new or worsening dry cough or breathlessness needs prompt medical review. This is a different thing from the longer-term lung scarring that some inflammatory conditions can themselves cause: the old belief that methotrexate drives that scarring has not held up in modern studies, which find no increased risk, so it is not a reason to avoid the medicine. Methotrexate can also suppress the bone marrow where blood cells are made, so a persistent sore throat, fever, or unexplained bruising or bleeding needs an urgent blood test. It can strain the liver too, which usually causes no symptoms at all, and is precisely what the routine blood tests watch.

That is why regular blood monitoring is part of the treatment rather than an optional extra. The tests check the blood counts, the liver and the kidneys: frequently when starting or changing treatment, then at longer intervals once things are stable. Problems picked up this way are usually mild and reversible, often needing no more than a pause or an adjustment; it is unmonitored problems that cause harm. Our guide to rheumatology blood tests explains what is measured and why.

Alcohol deserves a plain word here, because alcohol and methotrexate can each affect the liver. The UK position is pragmatic rather than absolute: drinking within the national guideline of no more than 14 units a week, spread out rather than saved up, is considered acceptable for most people on methotrexate, and many choose to drink less. Heavy or binge drinking does not mix with it. Be honest with your team about what you drink; the monitoring only protects you if it reflects reality.

Because methotrexate quietens the immune system, infections are somewhat more likely and can run harder than they otherwise would. That calls for sense rather than fear: seek advice early rather than late when you are unwell, and make sure whoever treats you knows you take methotrexate. Live vaccines are generally avoided while you are on it, whereas the injected flu vaccine and the COVID-19, pneumococcal and shingles vaccines are not live and are actively recommended. The shingles vaccine is worth asking about specifically, because an older version was live and best avoided on methotrexate, whereas the one now used is not, and is offered to those who are eligible. Our guide to infections and arthritis medicines covers this ground properly, including what happens to the medicine itself when you are ill.

The other habit worth building is simple: tell every prescriber, dentist and pharmacist that you take methotrexate, every time. Some antibiotics must not be combined with methotrexate, and the safest approach is to treat any new medicine, including anything bought over the counter, as worth a quick check with a pharmacist first. Many people keep their monitoring booklet or an up-to-date medicines list with them for exactly this reason.

Methotrexate is not safe in pregnancy. It must be stopped well before trying to conceive, with a planned switch to a treatment that is compatible with pregnancy, and that timing needs specialist planning rather than a decision made alone: please do not stop or change it yourself. If you are taking methotrexate and think you may already be pregnant, contact your rheumatology team straight away. Breastfeeding while on methotrexate is also not recommended. For men, current UK guidance is reassuring: low-dose weekly methotrexate is not thought to affect a man's ability to father a healthy child, though it is still worth raising when a family is being planned. The wider picture, including the treatments that can safely continue through pregnancy, is covered in our guide to arthritis, autoimmune conditions and pregnancy.

Contact your rheumatology team or GP the same day if you develop:

• New, persistent or worsening breathlessness, or a dry cough that does not settle
• Fever, a persistent sore throat, or signs of infection that are not settling
• Unexplained bruising or bleeding
• Yellowing of the skin or eyes, or dark urine
• Severe mouth ulcers, or vomiting that stops you keeping anything down

If you think methotrexate may have been taken daily rather than weekly, contact your prescribing team, a pharmacist or NHS 111 promptly rather than waiting to see how you feel.

A hot, swollen joint together with fever needs same-day emergency assessment, never a routine appointment, because a joint infection must be excluded quickly, and that holds whether or not you take methotrexate.

Call 999 or go to A&E for true emergencies only: becoming severely unwell with suspected sepsis, for example a high fever with shaking, confusion, rapid breathing or feeling dramatically worse over hours. For urgent but less dramatic problems, NHS 111 or your GP is the right first call. And if it is the arthritis flaring rather than the medicine misbehaving, our guide to managing flares sets out how to respond.

Methotrexate carries a reputation harsher than its record. It has been used in rheumatology for decades, it remains the standard against which newer treatments are measured, and most people who take it settle into an uneventful weekly routine that keeps their arthritis quiet for years. The conditions of that success are not mysterious: one day a week, folic acid as prescribed, blood tests kept up, and a low threshold for asking questions. Reviews are also where the treatment proves itself in the other direction: examination, blood results and, where helpful, point-of-care ultrasound can show whether joint inflammation is genuinely controlled, so decisions to continue, adjust or add treatment rest on evidence rather than guesswork. A medicine understood is a medicine taken with confidence, and with methotrexate that confidence is well founded.

Is methotrexate a type of chemotherapy?

It is the same molecule that is used, at far higher doses, to treat some cancers, which is why the packet leaflet mentions cancer and why this worry is so common. In rheumatology it is used at a small dose once a week for a completely different purpose: calming an overactive immune system rather than destroying cells. At these doses it does not behave or feel like chemotherapy, and taking it bears little resemblance to what people picture when they hear the word.

How long does methotrexate take to work?

Methotrexate is slow to act. Most people begin to notice benefit after several weeks, and the full effect can take two to three months. Because of this, a steroid is sometimes used as a bridge to settle symptoms while methotrexate takes hold; our guide to steroids in rheumatology explains how. It is worth persevering through the early weeks rather than concluding too soon that it is not working.

Why have I been given folic acid as well?

Folic acid is a vitamin that is usually prescribed alongside methotrexate because it reduces side effects such as nausea and mouth ulcers without stopping methotrexate from working. How and when to take it is set by your prescriber as part of your weekly routine, so follow the prescription rather than adjusting it yourself, and ask your team if anything about the routine is unclear.

Can I drink alcohol while I am taking methotrexate?

In moderation, usually yes. Both alcohol and methotrexate can affect the liver, so UK advice is to stay within the national guideline of 14 units a week at most, spaced through the week rather than kept for one occasion, and plenty of people choose to drink less than that. Heavy drinking and binge drinking, on the other hand, should be avoided. Be honest with your team about what you drink, because your liver is checked at every monitoring blood test.

I want to try for a baby. What happens with my methotrexate?

Methotrexate is not safe in pregnancy and must be stopped well before trying to conceive, with a planned switch to a treatment that is compatible with pregnancy. Do not stop it on your own: speak to your rheumatology team so the timing and the alternative can be planned properly. If you think you may already be pregnant while taking it, contact your team straight away. Our guide to arthritis, autoimmune conditions and pregnancy covers the wider picture.