Neoplastic Diseases:

• Methotrax 2.5 mg is indicated for the treatment of gestational choriocarcinoma, chorioadenoma destruens, and hydatidiform mole.
• It is also used in acute lymphoblastic leukemia and, in combination with other chemotherapeutic agents, for advanced non-Hodgkin’s lymphomas.
• Additionally, it is used in the treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T-cell lymphoma), and lung cancers, particularly squamous cell and small cell types.

Rheumatoid Arthritis (including Polyarticular Juvenile Rheumatoid Arthritis): Indicated for adults with severe, active rheumatoid arthritis and for children with active polyarticular-course juvenile rheumatoid arthritis who have not responded adequately to, or cannot tolerate, first-line treatments including full-dose NSAIDs.

Psoriasis: Indicated for the symptomatic management of severe, resistant, and disabling psoriasis that does not respond sufficiently to other therapies.

Methotrexate inhibits the enzyme dihydrofolate reductase. This enzyme is necessary to convert dihydrofolates into tetrahydrofolates, which are essential for the synthesis of purine nucleotides and thymidylate. By blocking this process, methotrexate interferes with DNA synthesis, repair, and cell replication. Rapidly dividing cells—such as cancer cells, bone marrow cells, fetal cells, and cells of the oral and intestinal lining—are particularly sensitive to its effects. Methotrexate can slow the growth of malignant cells without causing permanent damage to normal tissues when their growth rate is lower. In psoriasis, where skin cell production is abnormally increased, methotrexate helps control excessive cell proliferation.

Neoplastic Diseases-

Choriocarcinoma and similar trophoblastic diseases: Orally or intramuscularly in doses of 15 to 30 mg daily for a five-day course. The courses are usually repeated for 3 to 5 times as required, with rest periods of one or more weeks interposed between courses, until any manifesting toxic symptoms subside. Since hydatidiform mole may precede choriocarcinoma, prophylactic chemotherapy with methotrexate has been recommended. Chorioadenoma destruens is considered to be an invasive form of hydatidiform mole. Methotrexate is administered in these disease states in doses similar to those recommended for choriocarcinoma

Acute Lymphoblastic Leukemia
▪ Induction dose: 3.3 mg/m2 in combination with prednisone 60 mg/m2 daily for 4 to 6 weeks
▪ Maintenance dose: Orally or IM administration 2 times a week in total weekly doses of 30 mg/m2
▪ Alternate maintenance dose: 2.5 mg/kg IV every 14 days. If and when relapse does occur, reinduction of remission can again usually be obtained by repeating the initial induction regimen

Lymphoma
▪ Burkitt’s tumor Stages I to II: 10 to 25 mg once a day for 4 to 8 days
▪ Burkitt’s tumor Stage III: Methotrexate is commonly given concomitantly with other antitumor agents
▪ Duration of therapy: All stages usually require several courses of therapy interposed with 7 to 10 day rest periods
▪ Lymphosarcoma Stage III: 0.625 to 2.5 mg/kg daily as a part of combination chemotherapy

Mycosis Fungoides: Early stage dosing: 5 to 50 mg once a week; alternatively, 15 to 37.5 mg 2 times a week may be used in patients who have responded poorly to weekly therapy

Breast Cancer: 40 mg/m2 intravenously on the 1st and 8th day every 4 weeks in combination with cyclophosphamide and fluoracil for 6-12 cycles

Head and Neck Cancer: 40 mg/m2 IV weekly until disease progression or unacceptable toxicity (3 weeks equals one cycle; goal is to complete at least six cycles).

Adult Rheumatoid Arthritis: Single doses of 7.5 mg once per week, Maximum dose: 20 mg/week in adults

Polyarticular-Course Juvenile Rheumatoid Arthritis: 10 mg/m2 once weekly

Psoriasis: Single dose: 10 to 25 mg once per week, maximum dose: 30 mg/week

Should be taken on an empty stomach. Best taken on an empty stomach. May be taken with meals to reduce GI discomfort. Avoid taking with milk-rich products.

• Alcoholism, alcoholic liver disease, or other chronic liver diseases
• Immunodeficiency conditions
• Pre-existing blood disorders (e.g., bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)
• Hypersensitivity to methotrexate
• Pregnant women with psoriasis or rheumatoid arthritis
• Women of childbearing potential
• Breastfeeding mothers
• Pregnancy should be avoided if either partner is on methotrexate—during therapy and for at least 3 months after (men), and for at least one ovulatory cycle after therapy (women)

• Common: Ulcerative stomatitis, leukopenia, nausea, abdominal discomfort
• Other: Malaise, fatigue, chills, fever, dizziness, reduced resistance to infection
• May cause fertility issues, low sperm count (oligospermia), and menstrual irregularities during and shortly after treatment

US FDA Pregnancy Category X. Should only be used in cancer treatment when benefits outweigh fetal risks. Contraindicated during breastfeeding.

• Methotrexate formulations or diluents containing preservatives must not be used for intrathecal administration or high-dose therapy.
• Patients receiving methotrexate should be carefully monitored for signs of toxicity.
• If adverse reactions occur, the dose should be reduced or the drug discontinued, and appropriate treatment measures should be taken. Leucovorin calcium may be used if necessary.
• If therapy is restarted, it should be done cautiously, considering the need for continued treatment and the risk of recurring toxicity.
• Persistent abnormalities in liver function tests and/or decreased serum albumin levels may indicate serious liver toxicity and require further evaluation.
• Folate deficiency may increase the risk of methotrexate toxicity.

Pediatric patients: Use only after carefully weighing the benefits against potential risks, especially when used alone or with other drugs.

Geriatric patients: Elderly individuals should be closely monitored for early signs of liver, bone marrow, and kidney toxicity.

Leucovorin is used to reduce toxicity and counteract the effects of methotrexate overdose. It should be administered as soon as possible.

Antidote preparations, Immunosuppressant

Store below 30°C in a dry place. Protect from light and moisture.