Methotrexate

• 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).

Boxed Warning                           5/2020

Indications and Usage (1)           5/2020

Dosage and Administration (2)    5/2020

Contraindications (4)                   5/2020

Warnings and Precautions (5)       5/2020

Methotrexate tablets are 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 methotrexate tablets (4, 5.1).
• ALL: The recommended dosage is 20 mg/m² 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/m² 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/m² orally once weekly; adjust dose to achieve an optimal response (2.4)
• Psoriasis: The recommended dosage is 10 mg to 25 mg orally once weekly until adequate response is achieved. (2.5)

Tablets: 2.5 mg methotrexate, yellow, round, uncoated, scored, flat tablets with a diameter of 6 mm and embossed with code "ORN57” on one side.

Lactation: Instruct not to breastfeed. (8.2)