PDR Health


What is methotrexate?

Methotrexate is an oral medication that is used to treat certain types of cancer. It belongs to a class of drugs called antimetabolites. Methotrexate interferes with the growth of cancer cells and inhibits their multiplication.


Health Benefits

Methotrexate has been found to be effective in the treatment of several types of cancer, including breast cancer, leukemia, and lymphoma. It is also sometimes used to treat other conditions such as psoriasis, rheumatoid arthritis, and Crohn’s disease.

What are the side effects of methotrexate?

The most common side effects of methotrexate include:




stomach pain or cramps

loss of appetite


dizziness or drowsiness


coughing or shortness of breath

dry mouth



joint pain or stiffness

Some of the more serious side effects that can occur with methotrexate include:

liver damage

kidney damage

pancreatitis (inflammation of the pancreas)

low blood counts (which can lead to infection or bleeding)

ulcers in the mouth or gastrointestinal tract

severe allergic reaction (anaphylaxis)

Dosage and Preparation

Methotrexate is available in tablet and injectable form. It is typically taken once a week, although the exact dosing schedule may vary depending on the condition being treated.

Before taking methotrexate, be sure to tell your doctor about all other medications you are taking (including over-the-counter drugs, herbs, and supplements). Also, let your doctor know if you have or have ever had liver disease, kidney disease, or any type of cancer.

It’s important to take methotrexate exactly as prescribed and to not skip doses. If you miss a dose, call your doctor for instructions on how to make up for it.

Do not drink alcohol while taking methotrexate. Alcohol can increase the risk of liver damage.

Methotrexate should be used with caution in people with compromised immune systems (such as those with HIV/AIDS or those taking immunosuppressant drugs).


Methotrexate can interact with other medications, herbs, or vitamins you might be taking. Therefore, before taking methotrexate, it’s important to let your doctor know about all other drugs you are taking (including over-the-counter medications, herbs, and supplements).

Some of the drugs that may interact with methotrexate include:

ACE inhibitors (such as lisinopril)

NSAIDs (such as ibuprofen)

diuretics (water pills)

methotrexate Sodium (a salt form of methotrexate)

tretinoin (such as Retin-A)

vitamins A, D, or K

Mechanism of Action

Methotrexate works by inhibiting the growth of cancer cells. It does this by interfering with their ability to metabolize folic acid, a nutrient necessary for cell proliferation.

Folic acid is converted into tetrahydrofolic acid, which is then used to produce DNA and other important cellular molecules. By blocking the conversion of folic acid into tetrahydrofolic acid, methotrexate inhibits the synthesis of DNA and other cellular components, ultimately leading to cell death.

Methotrexate also inhibits an enzyme called dihydrofolate reductase, which is needed for the metabolism of folic acid. This further reduces the amount of tetrahydrofolic acid available for DNA synthesis, leading to cell death.

Methotrexate is thought to be most effective against rapidly dividing cells, such as cancer cells. This is why it is used as a chemotherapy drug. However, because methotrexate inhibits the growth of all rapidly dividing cells (not just cancer cells), it can also cause side effects such as hair loss, nausea, and vomiting.

Research on Methotrexate

Methotrexate has been studied extensively and has been found to be an effective treatment for several types of cancer, including breast cancer, leukemia, and lymphoma.

In one study, methotrexate was found to be more effective than the chemotherapy drug 5-fluorouracil in the treatment of advanced breast cancer.

Methotrexate has also been studied as a treatment for other conditions, such as psoriasis, Crohn’s disease, and rheumatoid arthritis. While methotrexate is not a cure for these conditions, it can help to reduce symptoms and improve quality of life.


Methotrexate is rapidly absorbed from the gastrointestinal tract and is widely distributed throughout the body. It is metabolized in the liver and excreted in the urine.

The half-life of methotrexate ranges from 8 to 12 hours. This means that it takes about 8 to 12 hours for the level of methotrexate in your body to be reduced by half.

Methotrexate should be used with caution in people with liver disease, as it may accumulate in the liver and cause damage.

Pregnancy and Methotrexate

Methotrexate is classified as a Category X drug by the FDA, which means it is known to cause birth defects in humans. Women who are pregnant or planning to become pregnant should not take methotrexate.

It’s also important to note that methotrexate can stay in your system for several months after you stop taking it, so women who are trying to conceive should wait at least three months after their last dose before trying to get pregnant.

Alternatives to Methotrexate

If you are pregnant or planning to become pregnant, there are several alternative treatments available for the conditions that methotrexate is used to treat.

For cancer, alternatives include other chemotherapy drugs, radiation therapy, and surgery. For psoriasis, alternatives include topical treatments such as corticosteroids and calcipotriene. For Crohn’s disease and rheumatoid arthritis, alternatives include biologic drugs.