10 Things You Should Know About Methotrexate

Safe Use of Methotrexate Decreases Potential Side Effects

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Methotrexate is commonly prescribed and effectively used to treat rheumatoid arthritis and certain other rheumatic conditions. Methotrexate has the potential for side effects. Safety warnings about methotrexate should not be feared, but should be respected. To enhance patient safety, methotrexate must be taken according to directions. Here are 10 important things you should know about methotrexate.

1 - Methotrexate (brand names Rheumatrex, Trexall) is classified as a DMARD (disease-modifying anti-rheumatic drug).

Methotrexate is classified as a DMARD because it decreases pain and swelling associated with rheumatoid arthritis and it lessens joint damage and lowers the risk of long-term disability by slowing disease progression. Improvement from methotrexate may be seen at 6 weeks, but it may take 12 weeks or even 6 months of treatment for full benefit to be realized.

2 - Methotrexate was approved by the U.S. Food and Drug Administration in 1988 for the treatment of rheumatoid arthritis.

Methotrexate had been used to treat psoriasis and cancer prior to its approval for rheumatoid arthritis. It is also used to treat other rheumatic conditions including:

3 - Methotrexate interferes with certain enzymes which play a role in immune system function.

Methotrexate blocks the enzyme dihydrofolate reductase. By doing so, it affects production of a form of folic acid, which is needed for actively growing cells. It remains unclear exactly how methotrexate decreases arthritis activity.

4 - Methotrexate is taken one day a week for arthritis. It is not taken daily like most pills.

Methotrexate is available in 2.5 mg tablets. The starting dose for most adults with rheumatoid arthritis is 7.5 to 10 mg (i.e., 3 or 4 pills). The 3 or 4 pills are taken together once a week (i.e., the same day each week). As needed, the dose of methotrexate can be increased to 20 to 25 mg each week. Methotrexate is also available in an injectable form which most patients can self-inject.

5 - It's important to have liver function blood tests every 8 to 12 weeks to look for any liver-related side effects.

Methotrexate can cause abnormal liver function. It's important to routinely have blood drawn for liver panels so your doctor can monitor for unwanted side effects.

6 - Alcohol increases the risk of liver damage for people taking methotrexate.

The increased risk of liver damage is significant for people who are drinking alcohol while taking methotrexate. Ideally, you should not drink alcohol if you take methotrexate. At most, with your doctor's permission, you should have no more than two drinks per month.

7 - Other than abnormalities with liver function, the most common side effects associated with methotrexate are nausea and vomiting.

The side effects already named (nausea, vomiting, liver function) may be dose-dependent. If you have any of these side effects, adjusting the dose may eliminate the problem. Many patients experience no significant side effects while taking methotrexate. Other possible side effects include:

In general. methotrexate should not be taken by people with known liver or kidney disease. A rheumatologist may decide to prescribe methotrexate to people with mild liver or mild kidney disease -- but with vigilance and an abundance of caution. Also, the medication may need to be temporarily stopped before having surgery.

8 - All patients treated with methotrexate should take a folic acid supplement.

Since methotrexate is a folic acid antagonist, replenishing folic acid by taking a supplement daily helps to minimize certain side effects associated with taking methotrexate.

9 - Methotrexate should not be taken if you are pregnant or plan to become pregnant.

Methotrexate can cause serious birth defects as well as pregnancy complications. You should be using some form of contraception while taking methotrexate and for 3 months after you stop taking methotrexate. It's important to note that although a woman should not take methotrexate during pregnancy, taking the drug does not decrease the chance for future pregnancies.

10 - It's important to remind your doctor of all the medications you take (prescription and over the counter). Some medications and natural remedies may increase methotrexate toxicity.

Drugs known to increase methotrexate toxicity include the antibiotic Trimethoprim (Bactrim) and NSAIDs (nonsteroidal anti-inflammatory drugs), though often prescribed together with methotrexate, can affect the level of methotrexate. Your doctor and pharmacist will be aware of unsafe drug interactions.


American College of Rheumatology. Methotrexate. Michael Cannon M.D. Updated March 2015.

Arthritis Without Pain. Scott J. Zashin, M.D. July 2004.

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