Antimetabolite·Musculoskeletal & Rheumatology

Methotrexate

Rheumatoid arthritis, severe psoriasis, Crohn's disease

Authority requiredPBSDMARDTrexall, Methoblastin, Trexject (SC)2.5 mg tablet+2

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At a glance

Max Dose

30 mg/week

Caution: Freq

ONCE WEEKLY

Folic Acid

MANDATORY

High risk: Toxicity

CRITICAL

Cautions

Avoid / Cautions

Severe renal impairment, active liver disease, profound immunodeficiency, active severe infection. Pregnancy Category D. Highly teratogenic (causes neural tube defects/abortion). Both men and women must use strict contraception for 6 months post-cessation.

Where it stands

Rapid Summary

Overview

Folate antimetabolite. The absolute gold-standard, first-line Disease-Modifying Antirheumatic Drug (DMARD) for Rheumatoid Arthritis.

Clinical Focus

Low-dose methotrexate for inflammatory disease is ONCE WEEKLY. Daily dosing errors are a known fatal safety risk.

Bottom Line

Methotrexate is the anchor DMARD for rheumatoid arthritis and psoriasis with proven long-term efficacy, but requires strict folic acid supplementation, regular blood monitoring, and is absolutely teratogenic.

Formulation & Access

Brand Names

Trexall, Methoblastin, Trexject (SC)

Oral Routes

Tablets (2.5 mg, 10 mg).

Parenteral

Pre-filled syringes for SC injection (highly bioavailable, less GI upset).

Prescribing & PBS

Authority Required (PBS).

Indications & Use

Primary

PBSTGA

Rheumatoid arthritis, severe psoriasis, Crohn's disease.

Off-Label

OFF

Ectopic pregnancy termination.

Clinical Place

The anchor drug for RA. Often combined with biological agents.

Quick reference

Class & Role

Antimetabolite — Folate antimetabolite.

Route / Formulation

Tablets (2.5 mg, 10 mg). (Trexall, Methoblastin, Trexject (SC))

Usual Dose & Max

PO / SC 10-25 mg ONCE A WEEK. Usually taken on the same day every week (e.g., 'Methotrexate Mondays'). Max 30 mg/WEEK (For Rheumatology). Oncology doses are massively higher.

Key Indication Doses

Rheumatoid Arthritis: PO / SC 10-25 mg ONCE A WEEK. Usually taken on the same day every week (e.g., 'Methotrexate Mondays'). Folic Acid Rescue: PO 5 mg ONCE A WEEK (MANDATORY — taken 1 to 2 days AFTER the Methotrexate dose to reduce toxicity without blocking efficacy). Renal Impairment: Reduce dose if eGFR < 60. Avoid if eGFR < 30.

Best Uses

Key Risks

Haematological: Severe bone marrow suppression (pancytopenia, agranulocytosis) if overdosed or given daily. Hepatic: Hepatotoxicity, fibrosis, cirrhosis (especially with chronic alcohol use). Respiratory: Methotrexate pneumonitis (acute, potentially fatal hypersensitivity lung reaction). Gastrointestinal: Severe mucositis, mouth ulcers, nausea.

Key Interactions

Trimethoprim (Bactrim). Completely blocks folate synthesis at a different step. Co-administration causes catastrophic bone marrow failure. NEVER combine. NSAIDs, Penicillins, PPIs (Reduce renal clearance of methotrexate, spiking toxicity).

Monitoring

Strict FBC, LFTs, and U&E checking every 1-2 months. Withhold drug if WBC drops or transaminases triple. Warn patient to report any unexplained dry cough, breathlessness, or mouth ulcers instantly.

Clinical Pearl

The most common fatal prescribing error in rheumatology is writing '10 mg Daily' instead of '10 mg Weekly'. Always double-check the script. Consider writing 'Methotrexate MONDAYS' to enforce the weekly concept.

Access

Authority requiredTrexall, Methoblastin, Trexject (SC)2.5 mg tablet

Brand: Trexall, Methoblastin, Trexject (SC)
PBS status: Authority required
Formulation: Tablets (2.5 mg, 10 mg).

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