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 and in psoriasis is unknown.

TREXALL is a dihydrofolate reductase inhibitor indicated for the:

• Treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen (1.1)
• Treatment of adults with mycosis fungoides (1.1)
• Treatment of adults with relapsed or refractory non-Hodgkin lymphoma as part of a metronomic combination regimen (1.1)
• Treatment of adults with rheumatoid arthritis (1.2)
• Treatment of pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA) (1.3)
• Treatment of adults with severe psoriasis (1.4)

• 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 TREXALL (4, 5.1).
• ALL: The recommended dosage is 20 mg/m orally once weekly as a part of a combination chemotherapy maintenance regimen. (2.2)
• Mycosis fungoides: The recommended dosage is 25 mg to 75 mg orally once weekly as monotherapy; 10 mg/m 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 chemotherapy. (2.2)
• Rheumatoid Arthritis: The recommended starting dosage is 7.5 mg orally once weekly; adjust dose to achieve an optimal response (2.3)
• pJIA: The recommended starting dosage is 10 mg/m orally once weekly; adjust dose to achieve an optimal response (2.4)
• Psoriasis: The recommended dosage is 10 to 25 mg orally once weekly until adequate response is achieved. (2.5)

See package insert for complete information.

Common adverse reactions include ulcerative stomatitis, leukopenia, nausea, abdominal distress.

• In pregnancy for non-neoplastic diseases 
• History of severe hypersensitivity to TREXALL

• Serious Infections: Monitor patients for infection during and after treatment with TREXALL. Withhold or discontinue TREXALL for serious infections as appropriate. (5.11)
• Neurotoxicity: Monitor patients for neurotoxicity and withhold or discontinue TREXALL as appropriate. (5.12)
• Secondary Malignancies: Can occur with methotrexate. (5.13)
• Tumor Lysis Syndrome: Institute appropriate prophylactic measures in patients at risk for tumor lysis syndrome prior to initiation of TREXALL. (5.14)
• Immunizations and Risk Live Vaccines: Immunizations with live vaccines is not recommended. Follow current vaccination practice guidelines. (5.15)
• Infertility: Can cause impairment of fertility, oligospermia, and menstrual dysfunction. (5.16, 8.3)