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Methotrexate is a folic acid derivative that interferes with folic acid metabolism (folate antagonist). It is a cytotoxic agent (a chemical that is directly toxic to cells) with multiple characteristics and may be described as an antimetabolite, antineoplastic, and immunosuppressant. In the United States, methotrexate is also recognized by the trade names Folex and Mexate, or the generic name amethopterin.


Methotrexate is administered to cancer patients diagnosed with various malignancies. These conditions may include breast cancer , lung cancer, non-metastatic bone cancer, cancers associated with the head and neck, acute lymphocytic leukemia , meningeal leukemia, advanced non-Hodgkin's lymphomas , and uterine tumors. Certain other cancers may be treated with methotrexate as prescribed by the oncologist.


Methotrexate was granted FDA approval in 1986. Methotrexate is a highly effective chemical compound that targets a specific enzyme required by cells for normal function. When this enzyme activity is blocked by methotrexate, certain processes within the cell are shut down and cell death results. The growth of some normal cells may be affected by methotrexate. However, because this is a process associated with actively dividing cells, the accelerated rate at which cancer cells grow and divide make them more susceptible to the effects of methotrexate. Methotrexate may be given as a single agent, often followed by leucovorin rescue. Methotrexate may also be administered in a combination regimen with steroids to produce and maintain rapid remission of certain cancers or as part of an adjuvant therapy regimen with doxorubicin , cisplatin , or the BCD combination of bleomycin , cyclophosphamide , and dactinomycin .

Recommended dosage

Methotrexate is available is both injectable and tablet form. The injectable form may be given intravenously (IV), intramuscularly (IM), or intrathecal (directly into the spinal fluid). The dose amount varies over a wide range for patients receiving methotrexate. The final dose and treatment cycle will be determined by the oncologist based on what the medication is being used for, what cancer type is being treated, whether methotrexate is being used as a single agent or in concert with other anticancer drugs, and the method by which the medication is being administered. It is extremely important to take methotrexate in the correct timetable prescribed by the oncologist. If a dose is missed, the patient should not take the missed dose at a later time, or double the next prescribed dose. Rather, the patient should maintain the schedule prescribed and notify the oncologist about the missed dose.


To maximize treatment effects, patients receiving methotrexate should observe certain guidelines. Including any modifications given by the oncologist, these guidelines should include regular visits with the oncologist and laboratory testing for white blood cell count, kidney, liver, and bone marrow function. Avoid any immunizations not approved or prescribed by the oncologist. Avoid contact with individuals taking or that have recently taken oral polio vaccine, or individuals that have an active infection. When necessary wear a protective facemask. Avoid prolonged or direct exposure to sunlight, as some patients experience an increased sensitivity. Ask for specific instructions on oral hygiene procedures to reduce the risk of gum abrasion, and avoid touching the eye and nasal areas unless hands have been properly washed immediately prior to contact. To reduce bleeding and bruising complications, patients should exercise extreme caution when handling sharp instruments and decline participation in contact sports. Prior to treatment, the patient's medical history should be thoroughly reviewed to avoid complications that might arise from previous conditions such as gout, kidney stones or kidney disease, liver disease, chickenpox, shingles, intestinal blockage, colitis, immunosupression, stomach ulcers, mouth sores, or a history of allergic reactions to various drugs. The oncologist should also be made aware if the patient is pregnant or if there is the possibility the patient might be pregnant, or if the patient is a breast-feeding mother. Only prescribed medications or over-the-counter (OTC) drugs approved by the oncologist should be taken by a patient receiving methotrexate.

Side effects

The beneficial effects of methotrexate are usually accompanied by less desirable side effects. Side effects correlate in severity with dose amount and length of treatment. It is important to encourage the patient to discuss any presenting side effects. Some side effects do not require medical attention, but still cause the patient concern. Side effects that fall into this category may include loss of hair (alopecia ) and appetite (anorexia ), nausea and vomiting , skin rash with itching , pale skin tone, and the appearance of boils or acne. These side effects tend to diminish as the body adjusts to the therapy, or if they become bothersome, the oncologist may prescribe interventions. Side effects that should be reported immediately to the oncologist include mouth sores; back, lower side, joint or stomach pain; fever or chills; headaches; bloody or dark urine; drowsiness; dizziness; black tarry stools; bloody stools or vomit; diarrhea ; redness or pinpoint red spots on the skin; swelling of the feet or lower legs; the development of a cough or hoarseness; and shortness of breath.


Anti-inflammatory medications should be avoided while the patient is receiving methotrexate. These drugs elevate the effects of methotrexate to potentially harmful levels. Vaccines should be avoided due to the immuno-suppression action of methotrexate, and alcohol should be avoided to reduce the risk of liver complications.

Jane Taylor-Jones, Research Associate, M.S.



Anti-cancer drugs which prevent cells from growing and dividing by blocking the chemical reactions required in the cell to produce DNA.


Agents that inhibit or prevent the development of cancers by stopping the maturation and proliferation of malignant cells.


The combined chemotherapy treatment of bleomycin, cyclophosphamide, and dactinomycin.


Chemicals that are toxic to cells, and prevent their reproduction or growth.

Hodgkin's lymphoma

A human malignant disorder of lymph tissue that appears to originate in a particular lymph node and later spreads to the spleen, liver, and bone marrow.


Any chemotherapeutic agent which also has the effect of suppressing the immune system.


The antidote for high dose treatments of methotrexate.

Lymphocytic leukemia

An acute form of childhood leukemia characterized by the development of abnormal cells in the bone marrow and lymph cells found in blood-forming tissues.


Refers to the spread of a cancer from its place of origin to another site in the body.


A physician who specializes in the diagnosis and treatment of patients with cancer.

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methotrexate (meth-oh-treks-ayt) n. a drug that interferes with cell growth and is administered by mouth or injection to treat many types of cancer, including leukaemia in children and various solid tumours (see antimetabolite). It also affects the immune response and may be used in the treatment of rheumatoid arthritis and severe psoriasis.

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CMF Cement Makers' Federation
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CMF n. cyclophosphamide, methotrexate, 5-fluorouracil: the combination of chemotherapy drugs used in standard treatment for breast cancer.