Methotrexate

What it is and how it works

Mechanism of Action Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. The mechanism of action in rheumatoid arthritis, pJIA, and in psoriasis is unknown.

Indications

Methotrexate Injection is a folate analog metabolic inhibitor indicated for: • The following neoplastic diseases for the: o Treatment of adult and pediatric patients with acute lymphoblastic leukemia as part of a combination chemotherapy regimen. o Prophylaxis and treatment of adult and pediatric patients with meningeal leukemia. o Treatment of adult and pediatric patients with non-Hodgkin lymphoma. o Treatment of adult and pediatric patients with osteosarcoma as part of a combination chemotherapy regimen. o Treatment of adults with breast cancer as part of a combination chemotherapy regimen. o Treatment of adults with squamous cell carcinoma of the head and neck as a single agent. o Treatment of adults with gestational trophoblastic neoplasia as part of a combination chemotherapy regimen. • Treatment of adults with rheumatoid arthritis (RA). • Treatment of pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA). • Treatment of adults with severe psoriasis.

Dosage and administration (summary)

• Verify pregnancy status in females of reproductive potential before starting Methotrexate Injection. ( 2.1 , 4 , 5.1 ) • Neoplastic diseases: Refer to the prescribing information for disease specific dosing recommendations. Follow guidelines for high-dose regimens. ( 2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 , 2.9 ) • RA: Recommended starting dosage of 7.5 mg once weekly intramuscularly; adjust dose to achieve an optimal response. • pJIA: Recommended starting dosage of 10 mg/m 2 once weekly subcutaneously or intramuscularly; adjust dose to achieve an optimal response. • Psoriasis: Recommended dosage of 10 mg to 25 mg once weekly intramuscularly or intravenously.

Contraindications

Methotrexate Injection is contraindicated in: • Patients with history of severe hypersensitivity to methotrexate . • Pregnancy in patients with non-neoplastic diseases . • History of severe hypersensitivity to methotrexate. • Pregnancy: in patients with non-neoplastic diseases.

Warnings and precautions

• Secondary malignancies can occur. • Tumor lysis syndrome can occur in patients with rapidly growing tumors. • Immunizations and Risks associated with Live Vaccines: Immunizations may be ineffective. Live vaccines are not recommended due to risk of disseminated infection. • Infertility: Can cause impairment of fertility, oligospermia, and menstrual dysfunction. ( 5.16 , 8.3 ) Embryo-Fetal Toxicity Based on published reports and its mechanism of action, methotrexate can cause embryo-fetal toxicity, including fetal death when administered to a pregnant woman.

Pregnancy

Pregnancy Risk Summary Methotrexate Injection is contraindicated in pregnant women with non-neoplastic diseases. Based on published reports and its mechanism of action, methotrexate can cause embryo-fetal toxicity and fetal death when administered to a pregnant woman .

Storage and supply

Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) . Protect from light. After first puncture, store multiple-dose vials at 2°C to 8°C, and use within 30 days. Methotrexate Injection is a hazardous drug. Follow applicable special handling and disposal procedures. 1

Source: Methotrexate (Methotrexate) — US FDA prescribing information, 2025-06-10, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.