Last reviewed 2026-04-20 · How we verify

Trexall (methotrexate)

Antifolate that inhibits dihydrofolate reductase (DHFR), blocking DNA synthesis at high doses (oncology) and suppressing inflammation at low doses (autoimmune).

Methotrexate is one of the most important drugs in medicine, serving dual roles in oncology and rheumatology. First approved in 1953, it remains the anchor DMARD for rheumatoid arthritis and a cornerstone of ALL chemotherapy. Available generically worldwide. WHO Essential Medicine.

At a glance

Mechanism of action

Methotrexate was one of the first chemotherapy agents, developed by Sidney Farber who used aminopterin to achieve the first remission in childhood leukemia in 1948. At high doses it kills rapidly dividing cancer cells by blocking folate-dependent DNA synthesis. At low weekly doses, it suppresses inflammation through adenosine-mediated mechanisms and is the anchor drug for rheumatoid arthritis. It is on the WHO Model List of Essential Medicines for both cancer and autoimmune indications.

Approved indications

• Acute lymphoid leukemia
• Burkitt's lymphoma
• Carcinoma of female breast
• Crohn's disease
• Erythrodermic psoriasis
• Gestational trophoblastic neoplasia
• Juvenile idiopathic arthritis
• Juvenile rheumatoid arthritis
• Malignant tumor of head and/or neck
• Malignant tumor of lung
• Meningeal Leukemia
• Mycosis fungoides
• Non-Hodgkin's lymphoma
• Osteosarcoma of bone
• Plaque psoriasis
• Psoriasis
• Psoriatic arthritis
• Pustular psoriasis
• Rheumatoid arthritis

Boxed warnings

• WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, and SEVERE ADVERSE REACTIONS • Methotrexate tablets can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, methotrexate tablets are contraindicated in pregnancy. For neoplastic diseases, advise females and males of reproductive potential to use effective contraception [see Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)]. • Methotrexate tablets are contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis [Contraindications (4), Warnings and Precautions (5.2)]. • Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue methotrexate tablets as appropriate [Warnings and Precautions (5.3, 5.4, 5.5, 5.6, 5.7, 5.8)]. WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, and SEVERE ADVERSE REACTIONS See full prescribing information for complete boxed warning. • Methotrexate tablets can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, Methotrexate tablets are contraindicated in pregnancy. For neoplastic diseases, advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. (4, 5.1, 8.1, 8.3) • Methotrexate tablets are contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis. (4, 5.2) • Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue methotrexate tablets as appropriate. (5.3, 5.4, 5.5, 5.6, 5.7, 5.8)

Common side effects

• Elevated liver tests
• Nausea/vomiting
• Gastrointestinal reactions
• Ulcerative stomatitis
• Leukopenia
• Nausea
• Abdominal distress
• Stomatitis
• Thrombocytopenia
• Rash/pruritus/dermatitis
• Diarrhea
• Alopecia

Serious adverse events

• Interstitial pneumonitis
• Aplastic anemia
• Acute hepatitis
• Cirrhosis
• Fibrosis
• Thromboembolic events
• Intestinal perforation
• Hemorrhagic enteritis
• Anaphylaxis
• Vasculitis

Key clinical trials

• A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Etanercept in Subjects With Moderately Active Rheumatoid Arthritis Despite DMARD Therapy (Phase 4)
• Baricitinib in Patients With Relapsing or naïve Dermatomyositis: a Multicenter Randomized Controlled Trial (BIRD) (Phase 3)
• Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT in JIA) (Phase 4)
• Phase III Randomised Study on Liposomal Cytarabine (DepoCyte®) vs. Intrathecal Triple for CNS-Treatment During Maintenance Therapy in High-Risk Acute Lymphoblastic Leukemia Patients in NOPHO ALL 2008 (Phase 3)
• A PHASE I/II STUDY OF RAPAMYCIN (SIROLIMUS) IN COMBINATION WITH METHOTREXATE (MTX) AND CYCLOSPORINE (CPS) IN PATIENTS UNDERGOING MARROW TRANSPLANTATION FROM RELATED DONORS MISMATCHED FOR ONE HLA ANTIG (Phase 1)
• A Randomised, Double-blind, Parallel Group, Multicentre Clinical Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Immunogenicity of SB2 Compared to Remicade® in Subjects With Moderate to S (Phase 3)
• A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy of Methotrexate as Remission Maintenance Therapy After Remission-Induction Therapy With Tocilizumab and Gl (Phase 2)
• Intralesional Methotrexate Injections for the Treatment of Nail Psoriasis: an Intra-subject Randomized Controlled Trial (Phase 4)

Patents

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Trexall CI brief — competitive landscape report
• Trexall updates RSS · CI watch RSS
• Generic (originally Lederle Laboratories) portfolio CI