Common brand names

• Jylamvo
• Trexall
• Various
• Xatmep

How it is administered

Methotrexate can be administered in several ways, depending on the specific formulation and indication:

• Oral tablets and oral solution: Taken by mouth, usually once weekly. Available as 2.5 mg tablets or as a 2 mg/mL oral solution.
• Injection: Can be given intravenously (IV), intramuscularly (IM), subcutaneously (under the skin), or intrathecally (into the spinal fluid). Injectable forms come in various strengths and may be with or without preservatives.

The route and dose depend on the disease being treated, age, and other factors. For blood cancers like non-Hodgkin lymphoma, methotrexate is often part of a combination chemotherapy regimen and may be given by mouth or injection.

How it works

Methotrexate works by inhibiting an enzyme called dihydrofolate reductase. This enzyme is necessary for cells to make DNA and replicate. By blocking this enzyme, methotrexate prevents rapidly dividing cells, such as cancer cells, from growing and multiplying.

Because it targets cells that are actively dividing, methotrexate is especially effective against cancers of the blood and lymphatic system, where cells tend to multiply quickly. However, it can also affect other rapidly dividing cells in the body, which is why side effects can occur in tissues like the bone marrow, digestive tract, and skin.

In the context of blood cancers, methotrexate is used to slow or stop the growth of malignant cells, either as a single agent or in combination with other chemotherapy drugs. Its effects on DNA synthesis make it a cornerstone in the treatment of various hematologic malignancies.

Who should take it

Methotrexate is indicated for adults and children with certain blood cancers, including:

• Acute lymphoblastic leukemia (ALL): As part of a combination chemotherapy maintenance regimen.
• Non-Hodgkin lymphoma: For adults with relapsed or refractory disease, often as part of a metronomic (frequent, low-dose) combination regimen.
• Mycosis fungoides (cutaneous T-cell lymphoma): As a single agent or in combination.

Methotrexate may also be used for other cancers and some autoimmune diseases, but in the context of blood cancers, it is a key part of multi-drug chemotherapy regimens. The specific regimen and dosing depend on the type and stage of cancer, as well as patient factors such as age and organ function.

Who should not take it

Methotrexate should not be taken by:

• Pregnant women being treated for non-cancerous conditions, due to the risk of severe birth defects and fetal death. For cancer treatment, risks and benefits must be carefully weighed.
• Patients with a history of severe hypersensitivity reactions (including anaphylaxis) to methotrexate.
• Patients with severe liver disease, significant kidney impairment, or active serious infections should generally avoid methotrexate unless the benefits outweigh the risks.

Methotrexate is also contraindicated in patients who cannot be closely monitored for blood counts, liver, and kidney function, as it can cause serious, sometimes life-threatening side effects.

Commonly used with

Methotrexate is often used in combination with other chemotherapy drugs for blood cancers. For non-Hodgkin lymphoma and acute lymphoblastic leukemia, it may be combined with agents such as:

• Vincristine
• Cyclophosphamide
• Doxorubicin
• Cytarabine
• Prednisone or other corticosteroids

The exact combination depends on the specific cancer type and treatment protocol.

Commonly tested with

Methotrexate is commonly tested with other chemotherapy agents in clinical trials for blood cancers. These include:

• Vincristine
• Cyclophosphamide
• Doxorubicin
• Cytarabine
• Prednisone
• Leucovorin (used as a "rescue" agent to reduce methotrexate toxicity)

Methotrexate is also tested in regimens with newer targeted therapies and immunotherapies, depending on the specific clinical trial and disease subtype.