Medication

Methotrexate

An old, inexpensive tablet or injection for severe psoriasis and psoriatic arthritis. It is taken once a week, not daily, and it needs regular blood tests.
Dr. Schwarz, MD · Board-certified dermatologistLast reviewed September 8, 2026
16:9 hero for Methotrexate. Never cropped: the tone strip and the corner logo depend on the full frame.

Start here

The most important thing here is the schedule: methotrexate for psoriasis is once a week, and people have died from taking it daily by mistake. A dose you should not have taken is an emergency, not a wait-and-see. Beyond that it is genuinely useful, cheap, it treats joints as well as skin, and slow, so give it three months before judging. Take the folic acid, and know that this drug cannot be taken around a pregnancy by either partner, so contraception is part of the conversation from the first appointment.

— Dr. Schwarz, Board Certified Dermatologist

Key Facts

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Also calledTrexall, Otrexup, Rasuvo, Xatmep, MTX, amethopterin
Drug classAntimetabolite and folate antagonist, a conventional systemic immunosuppressant
Taken asTablet once weekly, or an injection under the skin once weekly
Typical courseLong term, often years, while it keeps working and blood tests stay normal
Time to workFirst change at 4 to 8 weeks, judged at about 3 months
Prescription onlyYes

What It Is

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Methotrexate is a tablet or injection used for severe psoriasis, psoriatic arthritis and rheumatoid arthritis, among other conditions. It has been used for psoriasis since the 1950s and was one of the first systemic treatments for it. It comes from cancer medicine, where the doses are much higher. Psoriasis doses are a small fraction, and at that level it acts as an immune-calming drug rather than chemotherapy. It is taken once a week — the most important fact about it and the source of its most serious errors. It is cheap, generic, and it treats joint disease as well as skin, which is why it is still widely used even though newer injectable drugs clear skin better.

How It Works

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Methotrexate blocks dihydrofolate reductase, an enzyme cells need to recycle folate into the form used to build DNA. Rapidly dividing cells feel it first, which is why it slows the runaway skin-cell turnover in psoriasis plaques.

At the low weekly doses used for skin disease, a second effect matters more. Methotrexate makes adenosine build up outside cells, and adenosine damps down inflammatory immune cells. That quiets the overactive T-cell response behind psoriasis and psoriatic arthritis.

The same folate blocking causes the side effects. Mouth ulcers, nausea and low blood counts happen when normal fast-dividing cells, in the mouth lining, the gut and the bone marrow, run short of active folate. Folic acid restores enough folate for those tissues without undoing the treatment.

The drug is cleared by the kidneys. Poor kidney function means it stays in the body longer and toxicity rises sharply, which is why kidney tests are part of the monitoring.

Here is where Methotrexate acts in the skin, and what the others do instead.

About Methotrexate
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Skin basics
BARRIEREPIDERMISDERMIS28 daysQUIETS THE IMMUNE SIGNALARRIVES BY BLOODSLOWS SKIN CELLS DOWN

Methotrexate works on the immune signal throughout the body, not just where the rash is. That is what makes it powerful in widespread disease, and why it needs monitoring. Slows the fast-dividing cells and the immune signal together, taken once a week with folic acid. It needs regular blood tests.

Methotrexate arrives from the inside, carried to the skin by the blood, rather than crossing the barrier from outside. That is why it works everywhere at once, and why it needs monitoring.

In a plaque, skin cells travel from the bottom of the epidermis to the surface in four to six days instead of a month, and pile up as scale. This slows them back down, so the plaque thins.

The outer film of dead cells and oil. It holds water in and keeps irritants out, and it is thinner than a sheet of paper. Almost every dry, itchy, stinging skin problem starts here.

The outer layer, and the only one anything in a jar reaches. It renews itself constantly: a cell made at the bottom takes about a month to reach the surface and flake off. Most of what a skincare product does, it does here.

The living layer underneath, holding the blood vessels, the nerves and the collagen. It is where lasting change happens and it is hard to reach: most of what is sold for the skin never gets this far.

What It Treats

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Psoriasis
Psoriasis
Strong evidence
A long-established once-weekly tablet that damps down the immune overactivity, and it treats psoriatic arthritis at the same time, which is often why it is chosen. It needs regular blood tests for the liver and blood count, and folic acid alongside it. Alcohol is limited, and it is not used in pregnancy — ask your doctor.
Eczema
Eczema
Moderate evidence
A weekly tablet for long-running eczema. Cheaper than the injections and slower to work, with blood tests every few months. Ask your doctor about it before trying to conceive, and if you are pregnant or breastfeeding.
Scalp Psoriasis
Scalp Psoriasis
Moderate evidence
A long-established weekly tablet for psoriasis that is widespread, or scalp disease that has not budged on foams and solutions. It also treats psoriatic arthritis, which makes it a sensible choice when the joints are involved too. It needs regular blood tests, and it must not be taken in pregnancy.
Nail Psoriasis
Moderate evidence
An old, cheap weekly tablet that helps nails and also helps psoriatic arthritis, which is why it is often chosen when the joints are involved too. It needs regular blood tests, folic acid alongside it, and no alcohol excess. It is not used in pregnancy, and it must be stopped well before trying to conceive.

Not the Best For

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Alopecia Areata
Alopecia Areata
Limited evidence
An older immune-suppressing tablet used for extensive alopecia areata, sometimes with a low dose of steroid alongside. It has been overtaken by the JAK inhibitors for most people, and it stays useful where those are not available, not affordable or not suitable. It takes months to judge, needs regular blood tests, and must not be taken in pregnancy.
Contact Dermatitis
Contact Dermatitis
Limited evidence
A weekly tablet sometimes used for chronic hand dermatitis when avoidance and creams have genuinely failed. The evidence in contact dermatitis specifically is thin, mostly borrowed from eczema. It needs regular blood tests, and it is a specialist decision rather than a next step.
Completely clear skin
Doesn't work
Complete clearing is uncommon, and methotrexate clears less completely than the newer biologic injections. It stays in use because it is cheap, it treats joints, and it is taken at home.
The mark left where a plaque was
Doesn't work
The darker or lighter patch left behind is pigment change rather than psoriasis, and the drug does not act on it. It fades over months.

Forms

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Tablet:

Injection under the skin:

Oral liquid:

For those who cannot swallow tablets
Oral liquid
A solution exists, used mainly in children.

Strengths

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Almost all oral methotrexate comes as one small tablet strength, and the weekly dose is several tablets taken together on the same day. Count your tablets against the number on the label.

WeakestStrongest
2.5 mg tabletWeekly auto-injector25 mg per mL vial
The standard tablet
2.5 mg tablet
Nearly every oral prescription is written in multiples of this. A 15 mg weekly dose means six tablets, taken together, once a week.
The pre-filled pen
Weekly auto-injector
A fixed weekly dose in a single-use injector, so no question of how many to take.
The injectable liquid
25 mg per mL vial
Drawn up into a syringe when a pen is not used.

Dose

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This drug is taken once a week
Taking it every day can cause fatal bone marrow failure. Pick one day of the week, write it down, and keep to it.
Test dose
A single small dose, often 2.5 mg to 5 mg, with blood counts checked about a week later before going further. A safety check, not the treatment dose.
Starting dose
Commonly 7.5 mg to 15 mg once weekly, adjusted for age, weight, kidney function and other illnesses. Lower in older people and in reduced kidney function.
Going up
Small steps, usually 2.5 mg to 5 mg every few weeks with blood tests in between, until the psoriasis responds or side effects set the ceiling.
Usual dose
Most people settle between 15 mg and 25 mg once weekly. Above about 15 mg tablet absorption gets unreliable, a common point to switch to the injection.
Folic acid alongside it
It reduces nausea, mouth ulcers and blood count problems. Usually a daily dose on the days you are not taking methotrexate, or one larger weekly dose on a different day. It does not stop the drug working.
Total course
No fixed course. It continues as long as it works and blood tests stay normal, which for some people is years.

How to Take It

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When to take it: Once a week, on the same day every week. Choose a day you will remember and write it somewhere visible. Some people take the whole dose at once; some split it into two portions about twelve hours apart on the same day to reduce nausea. Do not spread it across different days unless you were told to. Take tablets with water, and with food if they upset your stomach. An evening dose means the tiredness and mild nausea happen while you are asleep. Folic acid goes on the other days, as prescribed. It is not a substitute for a missed methotrexate dose. With the weekly injection, keep to the same day and rotate the site.

If you miss a dose: Take it as soon as you remember if it is within about two days of your usual day. If longer, skip it and take the next on your usual day. Never take two weekly doses close together to catch up, and never take a daily dose to make up for a missed week. If you have taken more than one weekly dose, or taken it several days in a row, contact a doctor or a poison center straight away. Do not wait to see how you feel. This overdose is treatable caught early and dangerous when it is not.

What to Expect

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First dose | Taking it
Once a week, not daily, with folic acid on the other days. Nausea, tiredness or mouth soreness in the day or two after each dose is common early on; folic acid usually blunts it.
Weeks 1 to 2 | Settling in
Nothing visible in the skin yet.
Weeks 4 to 8 | Working
Plaques thin and spread less, thickness and scale first. Joint pain from psoriatic arthritis often improves in the same window, one reason it is chosen over a skin-only treatment.
About 3 months | Judge it here
Substantial improvement is the realistic target.
Beyond 3 months | Long term
Where it suits, the result holds while the dose continues, with regular blood tests. Some stay on it for years.
Many months | Nails
Nail psoriasis can improve, but slowly. Nails always lag behind the skin.

Side Effects

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This is a once-a-week drug, and the once-a-week part is the most important thing on the page. Taking it daily by mistake causes serious harm. Folic acid handles most of the everyday side effects.

Common — expected, and they settle

  • Nausea on dosing day Often better taken at night, or split over the day.
  • Tiredness for a day or two after Sometimes called the methotrexate hangover.
  • Mouth sores Folic acid usually prevents them.
  • Hair thinning Mild, and it reverses.

Tell your doctor — worth a call, not an emergency

  • Mouth sores that keep coming back Your folic acid may need changing.
  • A new cough or shortness of breath Get it checked rather than waiting.
  • Rising liver enzymes or a falling blood count: From your routine blood tests.
  • Any new medicine Especially trimethoprim, some antibiotics, and regular anti-inflammatories.
  • How much alcohol is reasonable Ask your doctor. It is a liver question, and the answer is personal.

Stop and get care

  • Fever with mouth ulcers and feeling very ill: Can mean your blood counts have dropped.
  • Shortness of breath with a dry cough
  • Black stools, or vomiting blood
  • Taking it more than once in a week Call right away, even if you feel fine.

What to Avoid

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  • Taking it more than once a week This is the error that has killed people. There is no daily psoriasis dose. If you have taken extra doses, get advice the same day.
  • Skipping the folic acid Not optional. It reduces nausea, mouth ulcers and blood count problems without reducing how well methotrexate works.
  • Missing your blood tests The problems this drug causes show up in blood results before you feel them. Missed tests are the main way avoidable harm happens.
  • Regular or heavy drinking Alcohol and methotrexate both stress the liver. Most doctors ask people on it to keep alcohol low or stop, so agree an actual limit.
  • Trimethoprim antibiotics These block folate the same way methotrexate does, and together they can cause severe bone marrow failure. Make sure every prescriber knows you take methotrexate.
  • Starting new medicines without checking Over-the-counter ones count. Regular anti-inflammatory painkillers, some stomach acid drugs and several antibiotics raise methotrexate levels. Make it a decision rather than an accident.
  • Live vaccines Live-virus vaccines are generally avoided. Non-live vaccines, including the usual flu vaccine, are encouraged.
  • Sunbeds and burning Old sunburn can flare back up on methotrexate, and the drug adds to sun sensitivity.
  • Pregnancy while taking it Getting pregnant, or fathering a pregnancy, is covered in Ask Your Doctor, and applies to both partners.

Monitoring

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Methotrexate is watched by blood test, and the schedule is not optional. The problems it causes are silent until they are advanced.

Before starting: Full blood count, liver tests, kidney function, and a pregnancy test where relevant. Hepatitis B, hepatitis C, HIV and tuberculosis screening is standard, because the drug damps the immune system. A chest x-ray if there is any history of lung disease.

Early on: Blood counts and liver tests within a week or two of starting, and again after each dose increase. This is when a sudden drop in blood counts would show.

Once stable: Full blood count, liver tests and kidney function every one to three months, depending on the dose and what else you take, for as long as you are on the drug.

The liver over the long term: Years of methotrexate can scar the liver, and the risk rises with total lifetime dose, heavy alcohol use, obesity, diabetes and fatty liver disease. Biopsy used to be the check; most clinics now use a blood marker of scarring and a scan of liver stiffness.

The lungs: A rare but serious lung inflammation can occur. A new dry cough, breathlessness or fever means being seen, not waiting for the next appointment.

What to report between tests: Mouth ulcers, unexplained bruising or bleeding, sore throat or fever, dark urine, yellowing of the eyes or skin, severe nausea, any new cough or breathlessness.

If You Stop

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No taper, no physical withdrawal. It is stopped outright for serious infections, before some surgery, and whenever a pregnancy is being considered. Psoriasis generally returns over weeks to a few months. Joint symptoms often come back faster than the skin, which catches people out. The drug leaves the body within days, but the pregnancy advice runs far longer, for both partners, and the interval should come from your own doctor. If it is stopped because it stopped working rather than for side effects, it is usually replaced, since severe psoriasis rarely stays quiet on its own.

Cost

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Generic methotrexate tablets are among the least expensive systemic treatments in dermatology. Folic acid is cheap too. The weekly auto-injector pens cost considerably more, and coverage usually requires showing that tablets caused nausea or did not work well enough. Plain injectable vials are cheaper than the pens. The real cost is the monitoring, repeated blood tests and periodically a liver scan or blood marker. Usually covered, but they are appointments and not optional. Insurers frequently require a trial of methotrexate before approving a biologic, one reason it is still so often the first systemic drug tried.

Ask Your Doctor

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If you are pregnant, might be pregnant, or are planning a pregnancy: Methotrexate must not be taken in pregnancy. It causes miscarriage and serious birth defects. The advice covers both partners, and it must be stopped well in advance — ask the doctor managing your care how long.
If you are breastfeeding
It passes into breast milk and is not used while breastfeeding. Ask the doctor managing your care.
If you have a liver problem
Liver disease, fatty liver, hepatitis B or C, and regular drinking all count. Each raises the risk of liver damage.
If you have kidney disease
Reduced kidney function raises levels and toxicity sharply, so the dose is lowered or another drug chosen.
If you take a trimethoprim antibiotic
Trimethoprim and trimethoprim-sulfamethoxazole with methotrexate can cause severe bone marrow failure, so the combination is generally avoided.
If you start any new medicine
Regular anti-inflammatory painkillers and stomach acid tablets count. Several common drugs raise methotrexate levels, so every prescriber should know you are on it.
If you develop a cough or fever
A new dry cough or breathlessness counts too. A rare lung inflammation can occur, and fever may mean an infection you cannot fight as well.
If you develop mouth ulcers or bruising
Unusual bleeding or yellowing of the eyes counts too. These are the blood count and liver problems the monitoring exists to catch.
If you are due surgery or a vaccination
Methotrexate is sometimes paused around surgery, and live vaccines are generally avoided.

How It Compares

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Acitretin
Worse
an oral retinoid, not an immunosuppressant, so no infection risk and no blood count problems. It works less well alone for plaque psoriasis, dries the lips and skin badly, and cannot be used by anyone who might become pregnant for years afterwards.
Ciclosporin
Different job
works much faster than methotrexate and is used for severe flares, but it raises blood pressure and damages the kidneys over time, so it is a short-term drug rather than a years-long one.
An amber pill bottle labeled Otezla tipped over with white tablets spilling out16:9 hero for Apremilast (Otezla). Never cropped: the tone strip and the corner logo depend on the full frame.
Apremilast
Worse
a tablet with a much lighter monitoring burden and no blood tests, and better tolerated, but generally less effective for skin than methotrexate and considerably more expensive.
Biologic injections
Better
clear skin far more completely than methotrexate and are usually better tolerated. They cost far more, and most insurers ask for methotrexate to be tried first.
Phototherapy16:9 hero for Narrowband UVB Phototherapy. Never cropped: the tone strip and the corner logo depend on the full frame.
Phototherapy
Different job
no systemic risk at all and good evidence for plaque psoriasis, but it means repeated visits to a clinic, and it does nothing for psoriatic arthritis.
Methotrexate's case
Different job
It is cheap, taken at home, treats skin and joints together, and is well understood after seventy years of use. Its cost is the monitoring and the pregnancy restrictions.

Myths

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  • "It is taken every day like other tablets." It is not, and this is the most dangerous belief about this drug. It is once a week. Daily dosing by mistake has caused bone marrow failure and deaths. If you have taken it on more than one day in a week, get medical help the same day.
  • "It is chemotherapy." It is chemotherapy at doses many times higher than these. At psoriasis doses it is an immune-calming drug, and it does not cause the hair loss and severe illness people picture from cancer treatment, though mild thinning happens to some.
  • "Folic acid cancels it out." It does not. Folic acid is prescribed deliberately to reduce nausea, mouth ulcers and blood count problems, without meaningfully reducing how well methotrexate works.
  • "Blood tests are just a formality once you are stable." They are the only warning system this drug has. Liver damage and falling blood counts are silent until they are serious.
  • "Only women need to worry about pregnancy on it." The advice covers both partners. Men are asked to stop for a period before trying to conceive too. Ask your own doctor rather than assuming it does not apply.
  • "One drink will hurt you." The concern is regular and heavy drinking, not a single glass, because alcohol and methotrexate both stress the liver. Even so, agree a limit with your doctor rather than setting it yourself.

Questions Patients Ask

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How often do I take it?

Once a week, on the same day. Never daily. Daily dosing by mistake is the most dangerous error with this drug and it has been fatal. Get medical help the same day if it happens.

Why do I also have to take folic acid?

Methotrexate blocks folate, and the mouth ulcers, nausea and low blood counts come from that. Folic acid on the other days restores enough folate to reduce them without stopping the treatment working.

Do I really need all the blood tests?

Yes. Liver damage and falling blood counts cause no symptoms until they are advanced. The tests are the only early warning.

Can I drink alcohol?

The concern is regular drinking, not a single glass, because alcohol and methotrexate both stress the liver. Agree an actual limit with your doctor.

Can I take it if I want to have a baby?

No. It must be stopped well before trying to conceive, and the advice covers both partners. It causes miscarriage and serious birth defects. Ask your own doctor how far in advance.

How long before I know if it is working?

Give it about three months. First changes often show at four to eight weeks, but three months on a tolerated dose is the fair point to judge.

Is it chemotherapy?

It is chemotherapy at much higher doses. At psoriasis doses it acts as an immune-calming drug, and the experience is not comparable.

References

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