Folate antagonist / DMARD / antineoplastic Pregnancy: Contraindicated in pregnancy and breast-feeding in non-oncological indications. Methotrexate is a powerful human teratogen — increased risk of spontaneous abortion, intrauterine growth restriction and congenital malformations. Women must not become pregnant during therapy; effective contraception is required during treatment and for at least 6 months afterwards, and pregnancy must be excluded before starting. Sexually active male patients or their female partners should use reliable contraception during treatment and for at least 6 months after, and men should not donate semen during that period. Methotrexate may decrease fertility (oligospermia, menstrual dysfunction, amenorrhoea), usually reversible on discontinuation.

Methotrexate

Brand names: Maxtrex, Metoject, Nordimet, Zlatal

Methotrexate is the anchor disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis and other inflammatory arthropathies, given as a once-weekly oral or subcutaneous dose at the low doses used in rheumatology.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Rheumatoid arthritis: usual dose 7.5–15 mg ONCE WEEKLY orally; the schedule may be adjusted gradually to achieve an optimal response but should not exceed a total weekly dose of 20 mg, after which the dose should be reduced to the lowest possible effective dose (achieved in most cases within 6 weeks)

Route: Oral (methotrexate 10 mg tablets)

Frequency: ONCE WEEKLY — in rheumatoid arthritis and psoriasis methotrexate must only be taken once a week and the prescriber should specify the day of intake on the prescription

Max: Rheumatoid arthritis: total weekly dose must not exceed 20 mg. Psoriasis: the total weekly dose can be increased up to 25 mg.

SOURCE: UK SPC (eMC) for Methotrexate 10 mg Tablets, §4.2 (https://www.medicines.org.uk/emc/product/11723/smpc). SAFETY: dosage errors can result in serious adverse reactions including death — mistaken daily use of the recommended dose has led to fatal toxicity; methotrexate should only be prescribed by physicians with expertise in its use, and the prescriber should ensure the patient or carer can comply with the once-weekly regimen. PSORIASIS: before starting, give a test dose of 2.5–5.0 mg to exclude unexpected toxic effects; if appropriate laboratory tests are normal one week later, treatment may be initiated at the usual dose of 7.5–15 mg once weekly, increased as necessary up to a total weekly dose of 25 mg, then reduced to the lowest effective dose according to therapeutic response (most cases within 4 to 8 weeks). Liver function tests before starting and every 2 to 4 months during therapy. ELDERLY: use with extreme caution; consider a dose reduction because of reduced liver and kidney function and lower folate reserves. HEPATIC IMPAIRMENT: administer with great caution, if at all, in significant current or previous liver disease, especially alcohol-related. THIRD SPACE (pleural effusion, ascites): the half-life can be prolonged up to 4 times — dose reduction or discontinuation may be required. ROUTE CHANGE: if changing from oral to parenteral administration a dose reduction may be required due to the variable bioavailability of oral methotrexate — this SPC is for oral tablets only and does not state SC, IM, IV or intrathecal regimens, so the parenteral doses shown on this page must be sourced from a parenteral methotrexate SPC. FOLATE: the fetched UK SPC text does not state a folic acid supplementation regimen (the page's 'folic acid 5 mg weekly' is not supported by this source); US labelling advises folic or folinic acid supplementation without a UK dose. PAEDIATRIC: the fetched §4.2 contains no paediatric posology; the US label states a polyarticular juvenile idiopathic arthritis starting dosage of 10 mg/m² orally once weekly (US labelling — not per-kg, and not verified against a UK source). ONCOLOGY: high-dose oncology regimens are not in the fetched §4.2 — treatment with doses >100 mg/m² should not be initiated at urinary pH <7.0 (see §4.4).

Dose adjustments

Renal

Dose adjustments for methotrexate doses <100 mg/m² in renal impairment: creatinine clearance >60 ml/min — administer 100% of the dose; 30–59 ml/min — administer 50% of the dose; <30 ml/min — methotrexate must not be administered. Dosing may need further adjustment due to wide intersubject pharmacokinetic variability; if serum creatinine rises the dose should be reduced.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Significantly impaired hepatic function
Significantly impaired renal function (creatinine clearance less than 30 ml/min)
Pre-existing blood dyscrasias such as bone marrow hypoplasia, leukopaenia, thrombocytopaenia or significant anaemia
Alcoholism
Severe acute or chronic infections and immunodeficiency syndrome
Stomatitis, ulcers of the oral cavity and known active gastrointestinal ulcer disease
Pregnancy and breast-feeding
Hypersensitivity to methotrexate or to any of the excipients
Concurrent vaccination with live vaccines
Concomitant use with drugs with antifolate properties (e.g. co-trimoxazole)

Side effects

Bone marrow suppression — leukopaenia, thrombocytopaenia, anaemia
Ulcerative stomatitis, gingivitis, nausea, vomiting, diarrhoea, anorexia; gastrointestinal ulceration and haemorrhage
Elevated transaminases and hepatotoxicity (periportal fibrosis, cirrhosis, acute hepatitis with prolonged use)
Pneumonitis / interstitial pneumonitis (can be fatal) and interstitial fibrosis, dyspnoea, dry cough
Headache, dizziness, fatigue; erythematous rash, alopecia, pruritus
Infections and opportunistic infections; rarely Stevens-Johnson syndrome and toxic epidermal necrolysis

Interactions

Drugs with antifolate properties (e.g. co-trimoxazole) — must not be used concomitantly (§4.3)
Live vaccines — concurrent vaccination must not be carried out during methotrexate therapy (§4.3)
NSAIDs and other nephrotoxic medicines — affect methotrexate elimination or cause kidney damage; monitor renal function at shorter intervals (§4.4)
Oral antibiotics, penicillins, sulfonamides, probenecid, proton pump inhibitors, salicylates and other highly protein-bound drugs (oral anticoagulants, phenytoin, sulfonylureas, tetracyclines) — may increase methotrexate exposure and toxicity (US label §7)
Nitrous oxide anaesthesia — potentiates the effect of methotrexate (US label §7)

Clinical monograph

How it works

It inhibits dihydrofolate reductase and other folate-dependent enzymes; at low weekly doses its anti-inflammatory action is attributed largely to adenosine-mediated immunomodulation.

Prescribing in practice

It is dosed ONCE WEEKLY and inadvertent daily dosing causes severe, potentially fatal toxicity, so the weekly schedule must be reinforced at every step.
Bone marrow suppression, hepatotoxicity and pneumonitis are key risks requiring regular monitoring and prompt response to symptoms.
It is contraindicated in pregnancy and significant renal or hepatic impairment, and interacts dangerously with trimethoprim and other antifolates.

Monitoring

Monitor full blood count, renal function and liver function regularly per shared-care protocols, with folic acid co-prescribed to reduce toxicity as advised in the SPC.

Counselling the patient

Take it only once a week on the same chosen day and never daily.
Report sore throat, fever, breathlessness, persistent cough or unusual bruising urgently.
Avoid pregnancy, limit alcohol, and take folic acid as prescribed.

Evidence & guidelines

Decades of randomised trial and registry evidence establish methotrexate as first-line therapy and the backbone of combination DMARD treatment in rheumatoid arthritis.

Reference: NICE NG100; BSR guidelines; NPSA Patient Safety Alert; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways