Methotrexate is a generic drug prescribed to treat certain types of cancers, arthritis, and psoriasis in adults and some children. As with other drugs, methotrexate can cause side effects, such as fatigue and diarrhea.

Methotrexate is available as the brand-name drugs Otrexup and Rasuvo.

Methotrexate comes as an injectable solution. Methotrexate also comes in oral forms, but this article does not cover them.

Read on to learn about potential common, mild, and serious side effects of methotrexate injections. For a general overview about this drug’s uses and more, refer to this comprehensive methotrexate injection article.

Methotrexate has boxed warnings. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). For details, see the “Methotrexate: Side effect specifics” section.

Methotrexate injectable solution can cause certain side effects, some of which are more common than others. These side effects may be temporary, lasting a few days to weeks. However, if the side effects last longer than that, bother you, or become severe, be sure to talk with your doctor or pharmacist.

These are just a few of the more common side effects reported in methotrexate clinical trials:

Mild side effects can occur with methotrexate injections. This list doesn’t include all possible mild side effects of the drug. For more information, you can refer to the drug’s prescribing information.

Mild side effects that have been reported with methotrexate include:

These side effects may be temporary, lasting a few days to weeks. However, if the side effects last longer than that, bother you, or become severe, be sure to talk with your doctor or pharmacist.

Note: After the FDA approves a drug, it tracks and reviews side effects of the medication. If you develop a side effect from methotrexate and want to tell the FDA about it, visit MedWatch.

Methotrexate injectable solution may cause serious side effects. The list below may not include all possible serious side effects of the drug. For more information, you can refer to the prescribing information.

If you develop serious side effects, call your doctor right away. If the side effects seem life threatening or you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Serious side effects that have been reported and their symptoms include:

  • increased risk of lymphoma, which may include symptoms such as:
    • weight loss
    • tiredness
    • fever
    • chills
  • tumor lysis syndrome (cancer cells release harmful chemicals into the blood) when methotrexate is used for cancer treatment, which may include symptoms such as:
    • nausea or vomiting
    • diarrhea
    • loss of appetite
    • muscle spasms or loss of muscle control
    • heart palpitations
  • changes in levels of certain blood cells, which may include symptoms such as:
  • increased risk of muscle and bone damage (when methotrexate is used together with radiation therapy), which may include symptoms such as:
  • infertility problems in males and females (see “Note” below)
  • boxed warnings:

A boxed warning is the most serious warning from the FDA. For more information about these warnings, see the “Methotrexate: Side effect specifics” section.

Note: Sex and gender exist on spectrums. Use of the terms “male” and “female” in this article refers to sex assigned at birth.

ALLERGIC REACTION

For some people, methotrexate can cause an allergic reaction.

In general, symptoms of allergic reaction can be mild or serious.

Ways to manage

For mild allergic reaction symptoms, such as a mild rash, call your doctor right away. They may recommend treatments to help manage your symptoms. They’ll also let you know whether you should keep receiving methotrexate injections.

For severe allergic reaction symptoms, such as swelling or trouble breathing, call 911 or your local emergency number right away. These symptoms require immediate medical care because they can become life threatening. If you’ve had a serious allergic reaction to methotrexate injectable solution, your doctor may recommend a different medication instead.

Methotrexate injectable solution may cause several side effects. Here are some frequently asked questions about the drug’s side effects and their answers.

Does methotrexate cause long-term side effects?

It’s possible for methotrexate to cause long-term side effects. The risk of long-term problems increases with higher doses of methotrexate.

Methotrexate can cause damage to your liver, kidneys, or lungs that may not be reversible and may also require long-term treatment or management. Examples include cirrhosis, liver failure, kidney failure, and interstitial lung disease, which can cause scarring around the lungs. Methotrexate use can also cause problems in your brain and spinal cord.

Methotrexate has a boxed warning about these serious side effects. A boxed warning is the most serious warning from the FDA. For more information, see “Methotrexate: Side effect specifics” later in this article.

Methotrexate treatment may also increase your risk of developing a type of cancer called lymphoma. This may go away after treatment ends, but in some cases, it could require long-term treatment.

Talk with your doctor or pharmacist to learn more about the potential long-term side effects of methotrexate.

Can methotrexate cause dental side effects?

Dental problems were not reported in clinical trials of methotrexate. However, the drug can commonly cause painful mouth sores. For more information, see “Methotrexate: Side effect specifics.”

Talk with your doctor if you have any questions or concerns about dental side effects during treatment with methotrexate.

Is methotrexate safe to use during pregnancy?

No, methotrexate is not safe to use during pregnancy for conditions other than cancer. This is because methotrexate has been shown to have serious side effects on a developing fetus. The drug has a boxed warning about the risk of fetal harm if used during pregnancy. For details, see the next section, “Methotrexate: Side effect specifics.”

Learn more about some of the side effects that methotrexate injections may cause. To find out how often side effects occurred in clinical trials, see the drug’s prescribing information.

Boxed warnings

Methotrexate has a boxed warning about the following risks. A boxed warning is the most serious warning from the FDA. The warning alerts doctors and patients about drug effects that may be dangerous. If you have questions about these effects, talk with your doctor for more information.

Fetal harm

Methotrexate use during pregnancy can cause congenital anomalies (commonly known as birth defects). They can affect the head, brain, face, arms, legs, or heart. In addition, the drug can also cause pregnancy loss.

Due to these risks, doctors will typically only prescribe methotrexate during pregnancy to treat cancer. Avoid this medication for psoriasis or rheumatoid arthritis if you’re pregnant or plan to get pregnant.

If you’re sexually active and can become pregnant, tell your doctor before starting methotrexate. They’ll order a pregnancy test to check that you aren’t pregnant. Learn more about methotrexate and pregnancy.

Hypersensitivity reactions

Serious hypersensitivity reactions, including anaphylaxis, are possible after receiving methotrexate injectable solution. It’s not clear whether such reactions occurred in clinical trials of methotrexate injectable solution.

Hypersensitivity reactions are also known as allergic reactions. See the box titled “Allergic reaction” earlier in this article for more information about allergic reactions and what to do about them.

Serious side effects

If you develop any symptoms of serious side effects during therapy with methotrexate, call your doctor right away. They may temporarily or permanently stop methotrexate treatment. They’ll also recommend treatments for the side effect(s).

If you develop serious side effects that seem life threatening or you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Serious side effects may include:

  • Kidney problems: In some people, methotrexate can cause kidney damage, including kidney failure. People who already have kidney problems or take a high dose of methotrexate may have an increased risk of kidney damage. Your doctor will monitor your kidney function throughout treatment. Symptoms of kidney problems may include:
    • itching
    • changes in the amount of urine your body produces
    • swelling in your feet and legs
  • Lung problems: Serious lung problems are possible with methotrexate use. This includes interstitial pneumonitis, which can happen suddenly or last a long time. Lung problems were a rare side effect in the drug’s clinical trials. Your doctor will monitor your lung function during methotrexate treatment. Tell your doctor if you experience symptoms such as:
    • dry cough
    • unexplained weight loss
    • shortness of breath
  • Liver problems: Methotrexate can sometimes cause elevated liver enzymes. This blood test result was commonly reported in clinical trials. Small increases in liver enzymes can usually get better on their own. In rare cases, methotrexate can damage the liver. Talk with your doctor right away if you experience symptoms of liver problems, such as:
  • Serious skin reactions: Serious skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported in people receiving methotrexate. These reactions aren’t common and were reported after the drug was approved for use. Tell your doctor right away if you develop symptoms of a serious skin reaction, which may include:
    • body aches
    • fever
    • skin rash that blisters or peels
  • Serious gastrointestinal (GI) problems: There have been reports of perforation (tear) or inflammation and bleeding in the intestine in some people receiving methotrexate. In rare cases, bleeding is life threatening. These side effects were reported after the drug was approved for use. Your risk of serious GI problems with methotrexate is higher if you have ulcerative colitis or have ever had a peptic ulcer. Contact your doctor right away if you have any of the following symptoms during methotrexate treatment:
  • Nervous system problems: Methotrexate can cause central nervous system (brain or spinal cord) problems in some people. These problems can last for a short or long time, and in some cases, they can be permanent. Your doctor will check your nervous system during treatment and will likely stop methotrexate if problems occur. Symptoms may include:

Mouth sores

Methotrexate can cause mouth sores and ulcers (stomatitis) in some people. This is a common side effect reported in the drug’s clinical trials.

You may notice a burning feeling in your mouth, small open sores, blisters, or bleeding. The sores most often affect your cheeks, tongue, gums, or inside of your lips. Mouth sores are typically mild and go away on their own. In some cases, they may lead to more serious digestive system problems.

What you can do

Your doctor may recommend taking folic acid to help prevent mouth sores. Let your doctor know if you experience mouth sores during treatment with methotrexate. They can recommend ways to treat your sores and relieve pain.

Below is important information you should consider before receiving methotrexate injections.

Methotrexate injectable solution has boxed warnings. A boxed warning is the most serious warning from the FDA. For details, see the “Methotrexate: Side effect specifics” section.

Other precautions

Before starting methotrexate, discuss your health history with your doctor. Methotrexate may not be right for you if you have certain medical conditions or other factors affecting your health. Be sure to talk with your doctor if any of the following apply to you:

  • kidney or liver problems
  • ulcerative colitis
  • peptic ulcer
  • lung problems
  • have fluid in your stomach area or lungs
  • seizures or other neurologic problems
  • previous allergic reaction to this or a similar drug
  • pregnancy
  • breastfeeding
  • alcohol consumption

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.