Methotrexate: what it treats, how to take it, side effects
Last updated September 3, 2026.
Methotrexate is an antimetabolite - it slows the overactive cell growth and immune activity behind rheumatoid arthritis, psoriasis, and certain cancers. It is one of the most effective and most closely monitored drugs in the arthritis world, and it carries a rule that has saved lives: for arthritis and psoriasis, it is taken once a week, never once a day.
What does it treat?
Severe psoriasis; rheumatoid arthritis; polyarticular juvenile idiopathic arthritis in children; and, in combination with other chemotherapy, certain leukemias and lymphomas. It treats cancer by slowing cancer-cell growth, psoriasis by slowing skin-cell growth, and arthritis by calming immune-system activity.
How do you take it?
Exactly as directed, on the schedule your doctor sets - and for psoriasis, rheumatoid arthritis, and juvenile arthritis, that schedule is once a week. MedlinePlus states it without softening: some people who mistakenly took methotrexate once daily instead of once weekly experienced very severe side effects or died. The label's arthritis starting dose is 7.5 mg once weekly, or 2.5 mg at 12-hour intervals for 3 doses given as a once-weekly course; your doctor increases gradually. Most people also take folic acid to blunt the side effects - take it exactly as prescribed. Improvement takes 3 to 6 weeks, full benefit 12 weeks or longer. Expect regular lab tests before, during, and after treatment - they are how problems get caught early. Never stop without your doctor. If you use the liquid, measure with the supplied syringe, wear disposable gloves, and never use a kitchen spoon.
Side effects to know
- Common: dizziness, drowsiness, headache, swollen or tender gums, reddened eyes, and hair loss.
- Serious - the warning list: blurred vision or sudden loss of vision and seizures mean calling immediately. The boxed warning adds the organ list: signs of infection or unusual bruising or bleeding (bone marrow); nausea, extreme tiredness, yellowing of skin or eyes, or pain in the upper right stomach (liver); dry cough, fever, or shortness of breath (lungs); mouth sores, severe stomach pain, or black or bloody stools (stomach and intestines); fever with rash, blisters, or peeling skin; and decreased urination or swelling of the face, arms, or legs (kidneys). All of these mean calling your doctor immediately.
Who should not take it?
Pregnancy is the first rule: methotrexate can cause life-threatening birth defects or death of the unborn baby. If you can become pregnant, you take a pregnancy test before starting and use birth control during treatment and for 6 months after the final dose; if your partner can become pregnant, birth control continues during treatment and for 3 months after. A pregnancy during treatment means calling immediately. Do not breastfeed during treatment or for 1 week after the final dose. Flag past allergic reactions to methotrexate, liver disease, lung disease, kidney disease or dialysis, stomach ulcers or ulcerative colitis, immune conditions and past hepatitis B, shingles, or tuberculosis, and heavy alcohol use - alcohol plus methotrexate compounds the liver risk, so ask your doctor for the explicit rule. Proton pump inhibitors like omeprazole and esomeprazole interact. No vaccinations without your doctor's go-ahead. Sun: your skin will be more sensitive, so protective clothing and sunscreen. It may also cause permanent infertility in men and women - a real conversation to have before starting.
When is it an emergency?
Trouble breathing, wheezing, or swelling of the face, tongue, or throat is a 911 call. So is a seizure. Fever with chills, vomiting blood, or black tarry stools mean immediate care. For an overdose, call Poison Control at 1-800-222-1222. Pymander's escalation routing is built and tested specifically for this class of decision; see the safety architecture working paper.
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Common questions
Why is methotrexate taken once a week instead of every day?
Because it is powerful, and the weekly spacing is the safety margin. MedlinePlus states it plainly: people who mistakenly took methotrexate once daily instead of once weekly experienced very severe side effects or died. For arthritis and psoriasis, the weekly schedule is the prescription - set a phone alarm, anchor it to a day, and if you are ever unsure whether you took it, call your pharmacist before taking more.
Why do I take folic acid with methotrexate?
Methotrexate works by interfering with folate - that is the mechanism - and the interference is what causes many of its side effects, like mouth sores and stomach upset. MedlinePlus says your doctor will probably have you take folic acid to decrease the side effects. It does not cancel the benefit; it shields the healthy cells. Take it exactly as prescribed, usually on the non-methotrexate days.
Why does methotrexate need so many blood tests?
Because its serious effects are silent at first. Methotrexate can affect the bone marrow, liver, lungs, and kidneys before you feel anything - MedlinePlus says your doctor orders lab tests before, during, and after treatment to catch side effects early. Every skipped appointment is a blind spot on a drug where early detection is the whole game.
Can I drink alcohol while taking methotrexate?
Ask your doctor, and expect the answer to be little or none. MedlinePlus warns that methotrexate can cause severe liver damage, especially over long periods, and specifically tells you to ask about the safe use of alcoholic beverages while taking it - alcohol stresses the same liver the drug does. Disclose your drinking history honestly at the start; it changes the risk math.
Why did my doctor make me take a pregnancy test before starting?
Because methotrexate can cause life-threatening birth defects or death of the unborn baby. The rules are explicit: a pregnancy test before starting if you can become pregnant, birth control during treatment and for 6 months after the final dose, and - if your partner can become pregnant - birth control during treatment and for 3 months after. This is a plan-ahead drug for both men and women.
Can I get my flu shot while on methotrexate?
Not without asking first. MedlinePlus says do not have any vaccinations during methotrexate treatment without talking to your doctor - the drug suppresses the immune system, which changes both how you respond to a vaccine and which vaccines are safe for you. Your doctor will map which shots, and when, fit your treatment.