Methotrexate
Pronunciation: meth-oh-TREX-ate.
- Generic name
- methotrexate
- Brand names
- Trexall (United States, verified from its current DailyMed label), Jylamvo, Maxtrex, Methofill, Metoject, Nordimet, Zlatal (United Kingdom, verified from the NHS medicines page)
- Drug class
- Antifolate — dihydrofolate reductase inhibitor, used as an antineoplastic agent and as a disease-modifying antirheumatic drug (DMARD)
- Form
- Tablet, oral solution, pre-filled pen or syringe, and injection vial depending on product and country
- Route
- Oral (tablet, oral solution) and injection (subcutaneous, intramuscular, intravenous, intrathecal), depending on product and indication
- Legal status
- Prescription-only medicine, specialist-initiated and specialist-monitored
Availability and supply rules vary by country
Trade names by country: United States · United Kingdom · Canada
Australia: · Full directory
What methotrexate is and how it works
Methotrexate is an antifolate medicine. It blocks dihydrofolate reductase, an enzyme cells need to make DNA, and at the lower doses used in inflammatory disease it also alters adenosine signalling, which damps down immune activity. That gives it two very different working lives: as chemotherapy for certain cancers, and as a disease-modifying treatment for rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe psoriasis. The single most important safety point is the schedule. For those inflammatory conditions, and for the oral maintenance regimens on the label, methotrexate is taken ONCE EVERY WEEK on one named day — never every day. (1) (2) (3) (7) (4)
Taking methotrexate daily when a weekly dose was prescribed has caused severe injury and death, so the dosing day matters as much as the dose itself. Most people on weekly methotrexate are also prescribed folic acid, taken on a different day, to reduce side effects. Methotrexate must not be used in pregnancy for non-cancer conditions, and effective contraception is required by both women and men taking it. It needs regular blood tests covering blood counts, liver function and kidney function for as long as it is prescribed. Every decision about the dose, the schedule, the folic acid plan and the monitoring belongs to the prescribing specialist team.
Mechanism of action: how methotrexate works
Methotrexate is a folate analogue that competitively inhibits dihydrofolate reductase, depleting reduced folates needed for thymidylate and purine synthesis and thereby arresting DNA synthesis in rapidly dividing cells — the basis of its antineoplastic effect. At the lower weekly doses used in inflammatory disease, its anti-inflammatory action is attributed largely to inhibition of aminoimidazole carboxamide ribonucleotide transformylase with consequent adenosine accumulation, producing T-cell suppression and reduced inflammatory signalling. It is renally cleared, so renal function is the dominant determinant of exposure and of toxicity risk. (1) (5) (4)
What methotrexate is used for
Rheumatoid arthritis in adults
Methotrexate is labelled for rheumatoid arthritis in adults, where it acts as a disease-modifying antirheumatic drug rather than a painkiller. In this setting it is a ONCE-WEEKLY medicine and benefit builds over weeks to months. Your rheumatology team sets the dose, the weekly day, and the blood-test schedule. (1) (2) (7)
Polyarticular juvenile idiopathic arthritis
Methotrexate is labelled for polyarticular juvenile idiopathic arthritis in children. Paediatric dosing is weight-based and once weekly, and it is set and reviewed by the paediatric specialist team. Adult doses must never be applied to a child. (1) (2) (3)
Severe psoriasis in adults
Methotrexate is labelled for severe, disabling psoriasis in adults that has not responded adequately to other therapy. Like the arthritis indications, this is ONCE-WEEKLY treatment with regular blood, liver and kidney monitoring arranged by the prescribing team. (1) (2) (3)
Acute lymphoblastic leukaemia (maintenance therapy)
Methotrexate is labelled as part of a combination chemotherapy maintenance regimen for acute lymphoblastic leukaemia in adults and children. Oncology regimens differ from inflammatory-disease use in dose, route and schedule, and are governed entirely by the treating oncology protocol. (1) (2)
Mycosis fungoides and relapsed or refractory non-Hodgkin lymphoma
The US labels cover mycosis fungoides (a cutaneous T-cell lymphoma) in adults and relapsed or refractory non-Hodgkin lymphoma in adults. These are specialist oncology indications with protocol-defined dosing. (1) (2) (3)
Other autoimmune conditions, including Crohn's disease
Beyond the labelled indications, methotrexate is used in some other immune-mediated conditions such as Crohn's disease and multiple sclerosis. MedlinePlus records these as off-label uses, and the NHS describes methotrexate as a treatment for Crohn's disease and other autoimmune conditions. Where it is used this way it remains a once-weekly specialist medicine, prescribed on an individual assessment of benefit and risk. (3) (6)
Before taking methotrexate
Do not take / not appropriate for
- Methotrexate is contraindicated in pregnancy when it is being used for a non-cancer condition such as rheumatoid arthritis or psoriasis, because it can cause embryo-fetal toxicity including fetal death. A pregnancy test is required before treatment starts. Tell the prescriber straight away if you are pregnant, think you may be pregnant, or become pregnant during treatment. (non-neoplastic indications) (1) (2) (10)
- Methotrexate is contraindicated in anyone who has had a severe hypersensitivity reaction, including anaphylaxis, to methotrexate. (all products) (1) (2)
- Methotrexate for arthritis or psoriasis is never a daily medicine. If any label, packet, chart or verbal instruction seems to describe daily use for one of these conditions, treat that as an error and contact the prescriber, clinic or pharmacist before the next dose is due, because daily administration has resulted in death. (weekly-dosed indications) (1) (2) (3)
Tell your clinician about
- Whether you are pregnant, might become pregnant, are trying to conceive, or are breastfeeding — and what contraception you and your partner are using.
- Any liver problem, hepatitis, fatty liver disease, diabetes, obesity, or heavy alcohol use, because these raise the risk of liver injury.
- Any kidney problem or recent change in kidney function, because reduced kidney function slows the removal of methotrexate from the body.
- Any lung disease, or a persistent cough or breathlessness, because methotrexate can cause inflammation of the lungs.
- Any active or recent infection, or a weakened immune system.
- Every other medicine, vitamin, herbal product and supplement you take — especially NSAIDs such as ibuprofen, trimethoprim or co-trimoxazole, proton pump inhibitors such as omeprazole, probenecid, and any folic acid or folate-containing supplement.
- Any vaccination that has been offered to you or your child, because live vaccines are not recommended during methotrexate treatment.
How to take methotrexate
- For rheumatoid arthritis, juvenile idiopathic arthritis and severe psoriasis, methotrexate is taken ONCE A WEEK, on the same named day each week. It is not a daily medicine for these conditions.
- Know your day. The NHS advises taking it on the same day every week, and product packs usually carry a reminder of the correct day. Writing the day on a calendar or a phone reminder is a recognised way to keep it right.
- Keep weekly methotrexate physically separate from any daily medicines you take, so the two cannot be confused — the NHS gives this specific storage advice because daily mix-ups have caused serious harm.
- Swallow tablets whole with a drink of water, and wash your hands afterwards. If you have been given an oral liquid, measure it only with the oral syringe supplied, never a kitchen spoon.
- If folic acid has been prescribed alongside methotrexate, the NHS describes taking it on a different day from the methotrexate dose, because taking it on the same day can stop the methotrexate working properly. Your prescriber sets which day and which strength.
- Attend every blood test appointment for as long as you are on methotrexate. The tests are how the team checks your blood counts, liver and kidneys, and they are part of the treatment rather than an optional extra.
- Speak to your prescriber, clinic or pharmacist before making any change to the dose, the day, the form, or the folic acid plan — and before starting any new medicine, including ones bought without a prescription.
Procedures and treatment changes
Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (5) (6) (7) (8) (9) (10)
Missed dose
Methotrexate is not an ordinary missed-dose situation. MedlinePlus advises contacting your doctor right away if a dose is missed, and never taking two doses to make up for one. The NHS advises contacting your doctor or clinic for advice if a weekly dose is more than two days late. Ring the prescribing clinic or your pharmacist for instructions rather than working out a catch-up plan at home.
Overdose
Too much methotrexate — including a weekly medicine taken on consecutive days by mistake — is a medical emergency. In the United States, contact Poison Control on 1-800-222-1222, or call 911 if the person has collapsed, is having a seizure, cannot be woken, or is having trouble breathing. In the United Kingdom, contact 111 urgently, and the NHS specifically names accidentally taking daily doses instead of weekly as a reason to make that call. Take the medicine packet with you if you go for assessment. (3) (7)
Side effects
Many people take weekly methotrexate for years with manageable side effects, but the medicine can also injure the bone marrow, liver, lungs, kidneys and the lining of the gut and mouth. That is why regular blood monitoring is mandatory and why some symptoms need same-day medical attention rather than a wait-and-see approach.
Nausea, vomiting, loss of appetite or stomach pain
What to notice: Feeling sick, being sick, poor appetite or abdominal discomfort, often in the day or two after the weekly dose.
What to do: The NHS suggests simple foods, small frequent meals and sipping fluids to prevent dehydration. Tell your clinic if it is persistent or getting worse — the team can review the timing, the folic acid plan, or anti-sickness support. (8) (4)
Diarrhoea
What to notice: Loose or more frequent stools.
What to do: Keep fluids up. The NHS advises against taking other anti-diarrhoea medicines without checking with a healthcare professional first. Report diarrhoea that is severe, bloody or persistent to your clinic promptly. (8)
Mouth soreness and ulcers (stomatitis)
What to notice: Sore mouth, ulcers, or discomfort with eating and drinking.
What to do: Report mouth ulcers to the prescribing team promptly. Mucositis is a recognised methotrexate toxicity and the team will want to check your blood counts and review your folic acid arrangements. (1) (2) (3)
Tiredness, headache, hair thinning and sun sensitivity
What to notice: Feeling drained, headaches, some hair loss, or skin that burns unusually easily.
What to do: The NHS advises resting and staying hydrated for headaches and using paracetamol rather than NSAIDs, using SPF 30 or higher sunscreen and covering up in the sun, and avoiding driving if you feel affected. Hair thinning is usually temporary; raise it with your clinician if it troubles you. (8)
Signs of a low blood count or infection
What to notice: High temperature, chills, muscle aches, sore throat, mouth ulcers, unusual bruising, bleeding gums, blood in your urine, or vomiting blood.
What to do: Contact your specialist team, out-of-hours service or NHS 111 the same day for urgent assessment and an urgent blood count. Methotrexate suppresses the bone marrow, and these can be the first signs of it. (1) (8)
Signs of liver injury
What to notice: Yellowing of the whites of the eyes or of the skin, dark urine, pale stools, persistent nausea, or pain over the upper right abdomen.
What to do: Contact your prescribing team or NHS 111 urgently for assessment and liver blood tests. Your clinician will decide what happens to the medicine. (1) (5) (8)
Signs of lung inflammation (pneumonitis)
What to notice: A new or persistent dry cough, chest pain, or breathlessness, which can appear at any point during treatment.
What to do: Contact your specialist team or NHS 111 urgently on the same day. Methotrexate pneumonitis can develop at any dose and needs prompt medical assessment; the clinician you speak to will advise on the medicine itself. (1) (8) (4)
Signs of kidney problems
What to notice: Swelling of the ankles, feet or hands, passing much less urine than usual, or a marked change in urination.
What to do: Contact your prescribing team urgently for kidney blood tests. Reduced kidney function slows the clearance of methotrexate and raises the risk of toxicity. (1) (8) (4)
Serious warnings
Fatal harm from taking methotrexate daily instead of weekly — emergency
Symptoms: There may be no warning at first. Within days, a daily-dosing error can produce severe mouth ulcers, sore throat, fever, bleeding or bruising, profuse diarrhoea, and collapse from bone-marrow failure.
Action: If methotrexate prescribed as a weekly dose has been taken on more than one day, treat it as an emergency: contact Poison Control on 1-800-222-1222 in the United States, contact 111 urgently in the United Kingdom, or attend emergency care. The US label states that inadvertent once-daily administration has resulted in death, and antidote treatment exists but is time-critical. (1) (2) (3) (7)
Embryo-fetal toxicity — harm to an unborn baby — emergency
Symptoms: A missed period, a positive pregnancy test, or any suspicion of pregnancy during treatment or in the months after the last dose.
Action: Contact the prescribing team the same day. Methotrexate can cause severe birth defects and fetal death, is contraindicated in pregnancy for non-cancer conditions, and requires a pregnancy test before treatment starts. The label directs females of reproductive potential to use effective contraception during treatment and for 6 months after the final dose, and males to use effective contraception during treatment and for 3 months after the final dose. (1) (2) (3) (10)
Myelosuppression (bone-marrow suppression) — urgent
Symptoms: Fever, sore throat, mouth ulcers, unusual bruising or bleeding, extreme fatigue or breathlessness.
Action: Seek urgent medical assessment and an urgent full blood count. Methotrexate can cause severe pancytopenia, anaemia and leukopenia, which is why scheduled blood-count monitoring is a condition of treatment. (1) (2) (4)
Hepatotoxicity — liver injury, fibrosis and cirrhosis — urgent
Symptoms: Jaundice, dark urine, pale stools, persistent nausea, or right-sided upper abdominal pain. Liver injury can also progress quietly, with no symptoms at all.
Action: Attend all scheduled liver blood tests and seek urgent assessment for any of these symptoms. The label records severe and potentially irreversible hepatotoxicity including fibrosis, cirrhosis and fatal liver failure. LiverTox notes that enzyme results alone are poorly predictive of fibrosis, so normal results do not remove the need for ongoing monitoring; risk is raised by heavy alcohol use, obesity, diabetes, other liver-toxic medicines, older age and higher cumulative dose. (1) (5)
Pulmonary toxicity — interstitial pneumonitis — urgent
Symptoms: New or worsening dry cough, breathlessness, chest pain, or fever without an obvious infection.
Action: Seek urgent medical assessment the same day. The label records acute or chronic interstitial pneumonitis, including irreversible and fatal cases, and it can occur at any dose and at any stage of treatment. (1) (2) (4)
Renal toxicity and reduced clearance in kidney impairment — urgent
Symptoms: Passing much less urine, swelling of ankles or hands, or a rapid change in kidney blood-test results.
Action: Seek urgent assessment and keep every kidney blood test appointment. Methotrexate can cause renal toxicity including irreversible acute renal failure, and because the kidneys clear the drug, impaired kidney function raises drug levels and toxicity. Dosage decisions in kidney impairment belong to the prescriber, guided by measured kidney function. (1) (2) (4)
Gastrointestinal toxicity, mucositis and severe skin reactions — urgent
Symptoms: Severe mouth or throat ulceration, severe or bloody diarrhoea, severe abdominal pain, or a spreading painful rash with blistering or peeling of the skin, mouth, eyes or genitals.
Action: Seek urgent medical assessment; go to emergency care for blistering or peeling rash. The label records stomatitis, diarrhoea, haemorrhagic enteritis and fatal intestinal perforation, and severe dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. (1) (2)
Severe hypersensitivity, including anaphylaxis — emergency
Symptoms: Sudden swelling of the lips, tongue or throat, difficulty breathing, wheezing, widespread hives, confusion, fainting, or skin turning blue, grey or very pale.
Action: Seek emergency medical help immediately — call 911 in the United States or 999 in the United Kingdom. A prior severe hypersensitivity reaction to methotrexate is a contraindication recorded in the boxed warning. (1) (2) (8)
Live vaccines and infection risk — important
Symptoms: This is a planning risk rather than a symptom: it arises whenever a vaccination is offered to you or to a child taking methotrexate.
Action: Tell any vaccinating clinician that methotrexate is being taken. Immunisation with live vaccines is not recommended during treatment, and the NHS specifies that children on methotrexate must not have the live nasal children's flu vaccine, with an inactivated vaccine used instead. Your prescriber and vaccination service will agree the right schedule. (1) (9)
Secondary malignancy — important
Symptoms: No specific early symptom; this is a long-term risk discussed as part of the decision to treat.
Action: Discuss long-term risks and the planned duration of treatment with your specialist. New cancers, including lymphoproliferative disease, are recorded in the label as a risk of methotrexate use. (1) (2)
Interactions
| Medicine or test | Effect | Action |
|---|---|---|
| NSAIDs — including ibuprofen, naproxen, diclofenac, aspirin at anti-inflammatory doses, and cold remedies containing an NSAID | NSAIDs increase methotrexate exposure by reducing its renal clearance, raising the risk of myelosuppression, mucositis and kidney injury. | Give the prescriber and pharmacist a full list of prescribed and over-the-counter painkillers before starting, and check with the pharmacist before buying any painkiller or cold remedy. For headaches, the NHS suggests paracetamol rather than an NSAID. Some rheumatology patients are deliberately prescribed both with monitoring — that is a prescriber decision, not a self-service one. (1) (8) (9) (4) |
| Trimethoprim and trimethoprim-sulfamethoxazole (co-trimoxazole) | Both are antifolates, so combining them with methotrexate adds folate blockade and markedly raises the risk of severe myelosuppression. | Make sure every prescriber and pharmacist who might treat an infection knows you take methotrexate, including out-of-hours and walk-in services. The prescriber will choose an alternative antibiotic or arrange specific monitoring. (1) (9) (4) |
| Proton pump inhibitors — omeprazole, esomeprazole, lansoprazole | Proton pump inhibitors can increase methotrexate levels by slowing its elimination, increasing toxicity risk. | Tell the prescriber and pharmacist about any indigestion or reflux medicine, including ones bought over the counter, so the combination can be reviewed and monitored. (1) (3) (9) |
| Probenecid | Probenecid reduces the renal clearance of methotrexate, raising blood levels and toxicity risk. | Tell the prescriber if probenecid is prescribed or being considered, so the combination and its monitoring can be planned. (1) |
| Folic acid, folinic acid and folate-containing supplements | Folate interacts with methotrexate by design. In inflammatory disease, prescribed folic acid reduces side effects; in cancer treatment, folate and folinic acid can decrease methotrexate's effectiveness. The NHS also advises taking prescribed folic acid on a different day from methotrexate, because same-day dosing can stop the methotrexate working properly. | Follow the exact folic acid plan your prescriber has written, including the strength and the day. Check with the prescriber or pharmacist before taking any multivitamin or supplement containing folate on top of it. (1) (3) (7) (9) |
| Live vaccines | Methotrexate suppresses immune function, so live vaccines carry a risk of vaccine-derived infection and are not recommended during treatment. | Tell the vaccinating clinician about methotrexate before any immunisation, for adults and children alike. Inactivated vaccines such as the standard influenza vaccine are normally used instead, on the prescriber's advice. (1) (9) |
| Alcohol and other medicines that can injure the liver | LiverTox identifies excessive alcohol intake, obesity, diabetes, concurrent hepatotoxic medicines, older age and higher cumulative methotrexate dose as risk factors for methotrexate liver injury. | Discuss your usual alcohol intake honestly with the prescribing team so they can advise a safe limit for you and set the right monitoring interval. (5) |
Pregnancy, breastfeeding, kidney/liver function, age
People who are pregnant, planning pregnancy, or breastfeeding
Methotrexate is contraindicated in pregnancy for non-cancer conditions and can cause birth defects and fetal death. A pregnancy test is required before starting. The label directs effective contraception during treatment and for 6 months after the last dose for females of reproductive potential, and for 3 months after the last dose for males. The NHS advises planning any pregnancy with your doctor well in advance, and states that if you become pregnant while taking methotrexate you should contact your doctor immediately for guidance rather than acting alone. For breastfeeding, the NHS describes weekly doses of 25 mg or less as potentially compatible with avoiding feeding for 24 hours after a dose and with infant blood monitoring — an individual assessment your clinician must make. (1) (2) (10)
Men taking methotrexate
The label directs males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the final dose. The NHS also records that methotrexate may reduce fertility and may damage sperm. Discuss family planning with the specialist team before any attempt to conceive. (1) (10)
Children and young people
Methotrexate is labelled for polyarticular juvenile idiopathic arthritis and for acute lymphoblastic leukaemia maintenance in children. Paediatric dosing is weight-based, specialist-set and, for arthritis, once weekly. Families are given a specific weekly day and a monitoring schedule; the NHS notes children taking methotrexate must not receive the live children's flu vaccine. (1) (2) (9)
People with reduced kidney function
The kidneys remove methotrexate from the body, so reduced kidney function leaves more of the drug circulating and increases toxicity. The current US label indicates dosage reduction or discontinuation, decided by the prescriber, for creatinine clearance below 90 mL/min, with close monitoring for adverse reactions. Kidney function is checked before treatment and repeatedly during it, and dehydration or a new kidney problem is a reason to contact the prescribing team. (1) (2) (4)
People with liver disease or higher liver risk
Existing liver disease, hepatitis, fatty liver, diabetes, obesity and heavy alcohol use all raise the risk of methotrexate liver injury. LiverTox records mild enzyme rises in a substantial minority of people on long-term therapy, and fibrosis in a smaller proportion, with clinically apparent liver disease now rare on modern weekly regimens compared with the historic daily regimens. Regular liver blood tests are a condition of treatment. (5)
Older adults
Older age is listed by LiverTox among the factors raising methotrexate liver risk, and kidney function commonly declines with age, which slows clearance of the drug. Prescribers take both into account when setting the dose and the monitoring interval. (5) (4)
Monitoring
Before starting
- Confirm the indication, the intended route and the weekly schedule in writing, and confirm the patient and any carer can state the correct dosing day.
- Pregnancy test in females of reproductive potential, and a documented contraception plan for females and males as directed by the label.
- Baseline full blood count, liver function tests and renal function including creatinine clearance.
- Review alcohol intake, body weight, diabetes, viral hepatitis status and any other hepatotoxic medicine.
- Assess baseline respiratory symptoms and lung disease before treatment starts.
- Take a complete medicines history covering NSAIDs, trimethoprim/co-trimoxazole, proton pump inhibitors, probenecid and folate-containing supplements.
- Agree the folic acid plan, including strength and the day it is taken relative to the methotrexate day.
- Review vaccination status and complete any needed live vaccines before treatment begins where feasible.
During treatment
- Scheduled full blood count, liver function tests and renal function at the interval set by the specialist protocol.
- LiverTox describes aminotransferase monitoring monthly for at least the first 6 months and roughly every 3 months thereafter, with more intensive monitoring if values exceed about three times the upper limit of normal.
- Recognise that normal liver enzymes do not exclude fibrosis — LiverTox notes enzyme monitoring is poorly predictive of fibrosis, so monitoring is combined with clinical assessment rather than relied on alone.
- Watch actively for cough, breathlessness, mouth ulceration, fever, infection, bruising or bleeding at every review.
- Recheck renal function after any dehydrating illness or any new interacting medicine, since clearance changes drive toxicity.
- Re-confirm at each review that the patient is taking the dose weekly, on the correct day, and that folic acid is being taken as planned.
- Reassess pregnancy status and contraception in patients of reproductive potential.
Storage
Keep methotrexate in its original container at room temperature, away from excess heat, light and moisture, and out of the sight and reach of children and pets. MedlinePlus records that methotrexate oral solutions expire 90 days after the container is first opened. The NHS gives one further storage instruction specific to this medicine: keep your weekly methotrexate physically apart from any medicines you take every day, so the two cannot be picked up by mistake. Return unwanted or expired methotrexate to a pharmacy for disposal rather than putting it in household waste.
Professional information
Clinician-facing context only. Apply the current local product labelling, the disease-specific protocol, and measured renal and hepatic function. Methotrexate dosing is not interchangeable between indications, routes or products.
United States
Indication: Rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and severe psoriasis
Dose summary: Oral methotrexate for these indications is administered ONCE WEEKLY; the boxed warning states that inadvertent once-daily administration has resulted in death. Paediatric dosing in pJIA is weight-based. The prescriber sets the weekly dose from the current label, titrating on response and tolerance, and co-prescribes folate supplementation per practice. StatPearls describes a typical weekly range of about 7.5–25 mg depending on the condition; the label remains the controlling document.
Renal context: Renal context: methotrexate is renally cleared and elimination is reduced in renal impairment. The current US label indicates dosage reduction or discontinuation for creatinine clearance below 90 mL/min, with close monitoring for adverse reactions; StatPearls describes dose reduction at GFR below 60 mL/min/1.73 m². Assess renal function at baseline, at each monitoring interval, and after any dehydrating illness or newly added interacting drug (NSAIDs, probenecid, proton pump inhibitors, trimethoprim-sulfamethoxazole). (1) (2) (4)
United States
Indication: Oncology — ALL maintenance, mycosis fungoides, relapsed/refractory non-Hodgkin lymphoma
Dose summary: Oncology dosing is protocol-defined and differs from inflammatory-disease dosing in dose, route and schedule; it is not once-weekly by default and must follow the treating regimen and the current label rather than being generalised from rheumatology practice. Folate and folinic acid can decrease methotrexate effectiveness in neoplastic disease, so supplementation decisions differ from the rheumatology setting.
Renal context: Renal context: renal clearance governs exposure and the same reduced-elimination principle applies; the label directs dosage reduction or discontinuation as appropriate for impaired renal function with close monitoring. High-dose regimens additionally depend on hydration, urinary alkalinisation and level monitoring as specified by the protocol, which the label and protocol define — not this page. (1) (2)
United Kingdom
Indication: Rheumatoid arthritis, psoriasis, Crohn's disease and other autoimmune indications
Dose summary: NHS patient guidance describes methotrexate for these conditions as a once-a-week medicine taken on the same day each week, available as tablets, oral liquid, and pre-filled pen or syringe injections, with prescribed folic acid taken on a different day from the methotrexate dose. Specific UK dose figures were not verified in this pass: the BNF monograph returned HTTP 403 to the fetcher and is therefore not cited, so UK numeric dosing is unresolved here and must be taken from the current UK SmPC or BNF directly.
Renal context: Renal context: not separately verified from a UK source in this pass — the BNF monograph was not retrievable. Apply the current UK SmPC for the specific product; the underlying pharmacology is unchanged, in that reduced renal clearance raises methotrexate exposure and toxicity risk, and renal function must be monitored throughout treatment. (6) (7) (4)
All other regions
Indication: Any methotrexate use
Renal context: Renal context: unresolved for regions outside the US in this pass. The renal-clearance principle applies universally, but numeric thresholds and adjustment rules must come from the applicable national label. (1)
Hepatic guidance
Hepatotoxicity is dual-pattern. High-dose intravenous therapy can produce marked, rapidly resolving aminotransferase elevations within 12–48 hours; chronic low-to-moderate weekly dosing produces mild elevations in roughly 15–50% of patients, with histological abnormality in about 30% and some degree of fibrosis in about 2–20% in the cited series. Historic daily regimens produced cirrhosis rates above 20% at 5–10 years, whereas clinically apparent liver disease is rare on modern weekly regimens. Serum enzymes are poorly predictive of fibrosis, so enzyme-only surveillance is insufficient; combine with risk-factor assessment (alcohol, obesity, diabetes, other hepatotoxic drugs, age, cumulative dose) and specialist hepatology input where indicated.
Overdose note
Leucovorin (folinic acid) rescue is the standard antidote and is time-critical; glucarpidase is used for severe toxicity accompanied by renal dysfunction. Supportive care includes hydration, urinary alkalinisation where the protocol specifies, haematological support, and serial methotrexate level and renal function measurement. Accidental daily administration of a weekly dose should be managed as a potentially fatal overdose, not as a minor dosing error — contact a poison centre for current, case-specific guidance. (1) (5) (4)
Frequently asked questions
How often do I take methotrexate — is it a daily tablet?
For rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis and other inflammatory conditions, methotrexate is taken ONCE A WEEK, on the same day each week. It is not a daily tablet for these conditions. The US prescribing information carries a boxed warning that inadvertent once-daily administration has resulted in death, and MedlinePlus records that people who mistakenly took it daily instead of weekly suffered very severe harm or died. If there is any doubt at all about your schedule, confirm it with your prescriber, clinic or pharmacist before the next dose is due. Oncology regimens use different, protocol-defined schedules set by the treating team. (1) (2) (3) (7)
What should happen if methotrexate was taken on the wrong day, or on several days in a row?
Treat repeated doses as an emergency rather than a minor slip. In the United States, contact Poison Control on 1-800-222-1222, or call 911 if the person is seriously unwell. In the United Kingdom, contact 111 urgently — the NHS names accidentally taking daily doses instead of weekly as a specific reason to call. Effective antidote treatment exists but works best early, so making the call quickly matters. For a single missed weekly dose, MedlinePlus advises contacting your doctor right away and never taking two doses to make up for one; the NHS advises contacting your doctor or clinic if the dose is more than two days late. (3) (7) (4)
Why have I been given folic acid as well, and when do I take it?
Folic acid is commonly prescribed alongside weekly methotrexate to reduce side effects such as nausea and mouth ulcers. The NHS describes a typical arrangement of one 5 mg folic acid tablet weekly taken on a different day from the methotrexate, and states plainly that folic acid should not be taken on the same day as methotrexate because it can stop the medicine working properly. The exact strength and day are set by your prescriber, and in cancer treatment the folate rules are different again — so follow the written plan you were given and ask the prescriber or pharmacist before adding any supplement that contains folate. (1) (3) (7) (9)
Can I take methotrexate if I am pregnant or trying for a baby?
No. Methotrexate is contraindicated in pregnancy for non-cancer conditions because it can cause severe birth defects and fetal death, and a pregnancy test is required before treatment starts. The label directs females of reproductive potential to use effective contraception during treatment and for 6 months after the final dose, and males to use effective contraception during treatment and for 3 months after the final dose. The NHS advises planning any pregnancy with your doctor well in advance, and says that if you do become pregnant while taking methotrexate you should contact your doctor immediately for advice rather than making changes on your own. Methotrexate may also reduce fertility in both men and women. (1) (2) (3) (10)
Can I take ibuprofen or buy medicines from the pharmacy while on methotrexate?
Check first. NSAIDs such as ibuprofen, and cold remedies containing them, increase methotrexate exposure and toxicity risk, and the NHS suggests paracetamol rather than an NSAID for methotrexate headaches. Indigestion medicines such as omeprazole and antibiotics such as trimethoprim or co-trimoxazole also interact and can be dangerous in combination. Tell every pharmacist and prescriber you deal with that you take weekly methotrexate — including out-of-hours and walk-in services — and let them choose what is safe for you. (1) (3) (8) (9) (4)
Why do I need blood tests all the time?
Because methotrexate's most serious harms can begin silently. The blood tests track your full blood count for bone-marrow suppression, your liver function for hepatotoxicity, and your kidney function because the kidneys clear the drug. LiverTox notes that liver enzyme results are poorly predictive of fibrosis, which is why monitoring continues even when results look normal. Keeping every appointment is part of the treatment, and your team will tell you how often testing is needed. (1) (5) (3)
Can I have my vaccinations while taking methotrexate?
Tell the vaccinating clinician you take methotrexate before any immunisation. Live vaccines are not recommended during treatment because methotrexate suppresses immune function, and the NHS specifies that children taking methotrexate must not have the live nasal children's flu vaccine. Inactivated vaccines, such as the standard adult flu vaccine, are normally used instead. Your prescriber and vaccination service will agree what is appropriate and when. (1) (9)
What symptoms mean I should get medical help urgently?
Get urgent medical assessment the same day for: a new or persistent cough, chest pain or breathlessness (possible lung inflammation); yellowing of the eyes or skin (possible liver injury); fever, sore throat, mouth ulcers, unusual bruising or bleeding (possible bone-marrow suppression); or much reduced urine output and swollen ankles (possible kidney problems). Call 911 in the United States or 999 in the United Kingdom for sudden throat or tongue swelling, severe breathing difficulty, confusion, fainting, or skin turning blue, grey or pale. (1) (8)
What is the mechanism of action of methotrexate?
Methotrexate is a folate analogue that competitively inhibits dihydrofolate reductase, depleting reduced folates needed for thymidylate and purine synthesis and thereby arresting DNA synthesis in rapidly dividing cells — the basis of its antineoplastic effect. At the lower weekly doses used in inflammatory disease, its anti-inflammatory action is attributed largely to inhibition of aminoimidazole carboxamide ribonucleotide transformylase with consequent adenosine accumulation, producing T-cell suppression and reduced inflammatory signalling. It is renally cleared, so renal function is the dominant determinant of exposure and of toxicity risk. (1) (5) (4)
What is the generic name of Methotrexate?
The generic name is methotrexate. It is sold under brand names including Trexall (United States, verified from its current DailyMed label), Jylamvo, Maxtrex, Methofill, Metoject, Nordimet, Zlatal (United Kingdom, verified from the NHS medicines page). (1) (2) (6) (4)
References
- METHOTREXATE tablet — full prescribing information (Alembic Pharmaceuticals Inc.)U.S. National Library of Medicine, DailyMed · United States · dated 2026-05 · accessed 2026-08-14 · source 1
- TREXALL (methotrexate tablet, film coated) — full prescribing information (Teva Pharmaceuticals, Rev. C 6/2026)U.S. National Library of Medicine, DailyMed · United States · dated 2026-06 · accessed 2026-08-14 · source 2
- Methotrexate — patient drug information (MedlinePlus)U.S. National Library of Medicine (MedlinePlus) · United States · accessed 2026-08-14 · source 3
- Methotrexate (StatPearls)NCBI Bookshelf — StatPearls · International · accessed 2026-08-14 · source 4
- Methotrexate — LiverTox: Clinical and Research Information on Drug-Induced Liver InjuryNCBI Bookshelf — LiverTox (NIDDK/NLM) · United States · accessed 2026-08-14 · source 5
- Methotrexate — NHS medicines overviewNational Health Service (UK) · United Kingdom · accessed 2026-08-14 · source 6
- How and when to take methotrexate — NHSNational Health Service (UK) · United Kingdom · accessed 2026-08-14 · source 7
- Side effects of methotrexate — NHSNational Health Service (UK) · United Kingdom · accessed 2026-08-14 · source 8
- Taking methotrexate with other medicines and herbal supplements — NHSNational Health Service (UK) · United Kingdom · accessed 2026-08-14 · source 9
- Pregnancy, breastfeeding and fertility while taking methotrexate — NHSNational Health Service (UK) · United Kingdom · accessed 2026-08-14 · source 10
Brand names by country
Single-ingredient methotrexate names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.
Priority countries
United States
- Rasuvo20 mg/.4mL, 10 mg/.2mL, 15 mg/.3mL, 12.5 mg/.25mL, 17.5 mg/.35mL, 22.5 mg/.45mL, 30 mg/.6mL, 7.5 mg/.15mL · medexus pharma inc.
- Otrexup12.5 mg/.4mL, 20 mg/.4mL, 10 mg/.4mL, 17.5 mg/.4mL, 15 mg/.4mL, 25 mg/.4mL, 22.5 mg/.4mL · antares pharma, inc.
- Trexall15 mg, 5 mg, 10 mg, 7.5 mg · teva women's health llc
- JYLAMVO2 mg/mL · shorla oncology inc.
- Xatmep2.5 mg/mL · azurity pharmaceuticals, inc.
United Kingdom
- Jylamvo (6)listed on nhs medicines page · not verified in this pass — see the current UK product information · Not verified in this pass; see the current UK product information
- Maxtrex (6)listed on nhs medicines page · not verified in this pass — see the current UK product information · Not verified in this pass; see the current UK product information
- Metoject (6)listed on nhs medicines page · not verified in this pass — see the current UK product information · Not verified in this pass; see the current UK product information
- Nordimet (6)listed on nhs medicines page · not verified in this pass — see the current UK product information · Not verified in this pass; see the current UK product information
- Methofill (6)listed on nhs medicines page · not verified in this pass — see the current UK product information · Not verified in this pass; see the current UK product information
- Zlatal (6)listed on nhs medicines page · not verified in this pass — see the current UK product information · Not verified in this pass; see the current UK product information
Canada
- METOJECT SUBCUTANEOUS
- METOJECT