Disease-Modifying Antirheumatic / Immunosuppressant Pregnancy: Contraindicated in pregnancy (non-oncological indications) and in breast-feeding. Methotrexate is a powerful human teratogen — foetal death, miscarriage and congenital abnormalities (craniofacial, cardiovascular, CNS, limb) have been reported; spontaneous abortion was reported in 42.5% of pregnant women exposed to low-dose methotrexate (<30 mg/week). Women must not become pregnant during therapy; effective contraception is required during treatment and for at least 6 months afterwards, with pregnancy excluded before starting. Sexually active male patients or their female partners are recommended to use reliable contraception during treatment and for at least 6 months after cessation; men should not donate semen during therapy or for 6 months after. Methotrexate may decrease fertility (oligospermia, menstrual dysfunction, amenorrhoea), usually reversible on discontinuation.

Methotrexate (Dermatology — Psoriasis)

Brand names: Methofar, Methofar XL

Methotrexate is a disease-modifying immunosuppressant taken ONCE A WEEK for psoriasis, rheumatoid and other inflammatory arthritis, and other immune-mediated conditions.

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: Psoriasis: test dose of 2.5-5.0 mg first; if laboratory tests are normal one week later, initiate treatment at the usual dose of 7.5-15 mg taken ONCE WEEKLY, increased as necessary up to a total weekly dose of 25 mg

Route: Oral

Frequency: ONCE WEEKLY — the prescriber should specify the day of intake on the prescription

Max: 25 mg total weekly dose in psoriasis (20 mg total weekly dose in rheumatoid arthritis)

CRITICAL DOSING WARNING (SPC §4.2): in the treatment of rheumatoid arthritis and psoriasis, methotrexate must only be taken ONCE A WEEK — dosage errors can result in serious adverse reactions, including death. Should only be prescribed by physicians with expertise in methotrexate and a full understanding of the risks; the prescriber should ensure the patient or carer can comply with the once-weekly regimen. Psoriasis: before starting, a test dose of 2.5-5.0 mg is advisable to exclude unexpected toxic effects. After response, reduce to the lowest effective dose according to therapeutic response, usually achieved within 4 to 8 weeks; aim for the lowest possible dose with the longest possible rest period, and encourage a return to conventional topical therapy where possible. Liver function tests before starting and repeated at 2 to 4 month intervals during therapy. Rheumatoid arthritis (other indication in the same SPC): usual dose 7.5-15 mg once weekly, adjusted gradually, not exceeding a total weekly dose of 20 mg, then reduced to the lowest effective dose (usually within 6 weeks). Elderly: use with extreme caution — consider dose reduction due to reduced liver and kidney function and lower folate reserves. Hepatic impairment: administer with great caution, if at all, to patients with significant current or previous liver disease, especially if alcohol-related. Third distribution space (pleural effusions, ascites): half-life can be prolonged up to 4 times normal — dose reduction or discontinuation may be required. Switching oral to parenteral administration may require a dose reduction due to variable oral bioavailability. Paediatric: no paediatric psoriasis dose is stated in this SPC — verify against a children's formulary before any paediatric use.

Dose adjustments

Renal

Dose adjustments for methotrexate doses <100 mg/m2 in renal impairment (SPC §4.2): creatinine clearance >60 ml/min — administer 100% of dose; 30-59 ml/min — administer 50% of dose; <30 ml/min — methotrexate must not be administered. Dosing may need further adjustment due to wide intersubject pharmacokinetic variability; creatinine clearance <30 ml/min is also a contraindication (§4.3).

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.

US labelling (FDA)

Reference — US labelling, may differ from UK

• Instruct patients and caregivers to take the recommended dosage as directed, because medication errors have led to deaths. (2.1, 5.9) • Verify pregnancy status in females of reproductive potential before starting methotrexate tablets. (4, 5.1) • ALL: The recommended dosage is 20 mg/m 2 orally once weekly as a part of a combination chemotherapy maintenance regimen. (2.2) • Mycosis fungoides: The recommended dosage is 25 to 75 mg orally once weekly as monotherapy; 10 mg/m 2 orally twice weekly as part of combination chemotherapy. (2.2) • Relapsed or refractory non-Hodgkin lymphoma: The recommended dosage is 2.5 mg orally two to four times per week as part of metronomic combination …

Source: US FDA prescribing information (openFDA / DailyMed), label dated 2024-06-04. Accessed 2026-06-12. US dosing and indications can differ from UK practice — use UK sources for prescribing decisions.

Contraindications

Significantly impaired hepatic function
Significantly impaired renal function (creatinine clearance less than 30 ml/min)
Pre-existing blood dyscrasias — bone marrow hypoplasia, leukopenia, thrombocytopenia 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 during methotrexate therapy
Concomitant use with drugs with antifolate properties (e.g. co-trimoxazole)

Side effects

Bone marrow suppression — leukopenia, thrombocytopenia, anaemia, bone marrow depression (most common; generally reversible)
Mucosal damage — ulcerative stomatitis, gingivitis, gastrointestinal ulceration and haemorrhage; nausea, vomiting, diarrhoea, anorexia
Hepatotoxicity — elevated transaminases, periportal fibrosis, cirrhosis, acute hepatitis
Pulmonary — pneumonitis, interstitial pneumonitis (can be fatal), interstitial fibrosis, dyspnoea, dry cough
Infections and reduced immunity, including opportunistic infections, herpes zoster and sepsis
Skin — erythematous rash, alopecia, pruritus, photosensitivity, acne; Stevens-Johnson syndrome and toxic epidermal necrolysis
Malaise, abnormal fatigue, chills and fever, dizziness, headache

Interactions

Antifolate drugs (e.g. co-trimoxazole, dapsone, pemetrexed, pyrimethamine, sulfonamides) — contraindicated/avoid; increased toxicity
NSAIDs and aspirin/salicylates — increase methotrexate exposure and the risk of severe adverse reactions
Oral, intravenous penicillin or sulfonamide antibiotics and oral antibiotics including neomycin — altered methotrexate exposure
Highly protein-bound drugs (oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, tetracyclines) — increased methotrexate plasma concentrations
Proton pump inhibitors and probenecid — increased methotrexate exposure
Hepatotoxic and nephrotoxic products — increased organ-specific adverse reactions
Nitrous oxide anaesthesia — potentiates the effect of methotrexate
Live vaccines — must not be given during methotrexate therapy (SPC §4.3)
NOTE: the UK SPC §4.5 was not captured in this bundle; the list above is drawn from SPC §4.3 plus the US labelling §7 and should be checked against the UK SPC

Clinical monograph

How it works

At these low doses it inhibits dihydrofolate reductase and other folate-dependent enzymes, producing anti-inflammatory and immunomodulatory effects.

Prescribing in practice

It is taken ONCE A WEEK — accidental daily dosing is a recognised cause of fatal toxicity, so the dose, day and tablet strength must be unambiguous and a single low tablet strength used to avoid confusion.
Folic acid is taken on a different day; monitor for bone-marrow suppression, hepatotoxicity and pneumonitis.
It is teratogenic (reliable contraception required) and interacts dangerously with trimethoprim/co-trimoxazole and with NSAIDs in renal impairment.

Monitoring

Monitor FBC, liver and renal function regularly (more frequently at initiation and after dose changes), and ask about new breathlessness or cough (pneumonitis).

Counselling the patient

Take it ONCE A WEEK on the same day — never daily; take folic acid on a different day.
Report sore throat, fever, mouth ulcers, breathlessness or unusual bruising.
Use reliable contraception, avoid pregnancy, and limit alcohol.

Evidence & guidelines

A first-line conventional DMARD for moderate-to-severe psoriasis and inflammatory arthritis, with strict weekly-dosing safety controls (NICE; MHRA/NPSA alerts).

Reference: BAD Methotrexate Dermatology Guidelines; MHRA MTX Safety; 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