Methotrexate oral tablet side effects: A detailed guide

Specifically, the Food and Drug Administration (FDA) has approved methotrexate oral tablet to treat:

• rheumatoid arthritis in adults
• severe psoriasis in adults
• juvenile idiopathic arthritis in children
• acute lymphocytic leukemia in adults and children
• T-cell lymphoma of the skin in adults
• certain types of non-Hodgkin’s lymphoma in adults

This article describes possible side effects of methotrexate oral tablet. You’ll also find information on cost savings and coupon options for methotrexate. You can explore this overview article to learn more about methotrexate oral tablet, including the drug’s uses and side effects, ways to save on cost, and more.

Methotrexate oral tablet is a generic version of the brand-name drug Trexall. Methotrexate also comes in an injectable form, but this form isn’t described in this article. To learn more about this form, talk with your doctor.

Boxed warnings

Methotrexate has boxed warnings about the following risks. A boxed warning is the most serious warning from the FDA.

• risk of harm to the embryo or fetus, including fetal death
• risk of serious allergic reaction, including anaphylaxis
• risk of serious side effects

For details about the risks of serious allergic reaction and serious side effects, see the “Side effects of methotrexate in detail” section below. For more information about the risk of fetal harm, see the “Warnings for methotrexate” section below.

More common side effects of methotrexate

Methotrexate oral tablet may cause mild or serious side effects. Below are some of the more common side effects of this medication.

Commonly reported side effects of methotrexate oral tablet include:

• mouth ulcers
• low white blood cell count*
• nausea
• upset stomach

* To learn more about this side effect, see the “Side effects of methotrexate in detail” section below.

Mild side effects of methotrexate

Methotrexate may cause certain mild side effects. Most often, mild side effects are temporary and can be easily managed. Tell your doctor or pharmacist if you have side effects that don’t go away or become bothersome.

Mild side effects of methotrexate oral tablet that occurred in studies include:

• chills
• diarrhea
• dizziness
• fatigue (low energy)
• malaise (feeling unwell)
• fever
• hair loss
• headache
• mild infection, such as the common cold
• mouth ulcers
• nausea
• upset stomach
• vomiting
• mild allergic reaction*

* To learn more about this side effect, see the “Side effects of methotrexate in detail” section below.

Methotrexate oral tablet may cause more mild side effects than those listed above. For details, see the drug’s prescribing information.

Serious side effects of methotrexate

Methotrexate may cause certain serious side effects. If you have any serious side effects from methotrexate oral tablet, call your doctor right away. But if you think you’re having a medical emergency or your side effects feel life threatening, take immediate action. Call 911 or a local emergency number, or go to the nearest emergency room.

After the Food and Drug Administration (FDA) approves a drug, it tracks and reviews side effects of the medication. Visit MedWatch’s website if you’d like to notify the FDA about a side effect you’ve had with methotrexate.

Serious side effects of methotrexate oral tablet that occurred in studies include:

• serious, possibly life threatening infections, including tuberculosis and pneumocystis pneumonia
• severe brain and spinal cord effects, including brain damage
• tumor lysis syndrome (a condition where tumors release their contents into your blood)
• certain cancers*
• risk of fetal harm†
• risk of serious side effects‡
• risk of serious allergic reaction‡

* To learn more about this side effect, see the “Side effects of methotrexate in detail” section below.
† Methotrexate oral tablet has a boxed warning for this side effect. A boxed warning is the most serious warning from the FDA. To learn more, see the “Warnings for methotrexate” section below.
‡ Methotrexate oral tablet has a boxed warning for this side effect. A  boxed warning is the most serious warning from the FDA. To learn more, see the “Side effects of methotrexate in detail” section below.

Common questions about side effects of methotrexate

Here are answers to some common questions about side effects of methotrexate oral tablet. If you have other questions, talk with your doctor or pharmacist.

Can methotrexate cause oral or dental side effects?

Yes, methotrexate can cause oral or dental side effects. Painful mouth ulcers are a common side effect reported in studies of methotrexate.

Gingivitis (inflammation of the gums) has also been reported in people taking methotrexate since it was approved for use. It’s not known for certain how often this side effect has happened or if methotrexate was the cause.

Talk with your doctor if you have questions about oral and dental side effects of methotrexate, including how to treat them.

Will lower doses of methotrexate cause fewer side effects than higher doses?

Possibly. In general, lower doses of a medication are less likely to cause side effects than higher doses.

In studies of methotrexate, researchers didn’t note whether lower doses caused fewer side effects than higher doses. Also, different side effects weren’t reported with different doses.

Talk with your doctor or pharmacist if you have questions about your methotrexate oral tablet dose and how it affects your risk of side effects.

Does methotrexate cause long-term side effects?

Yes, in some cases, methotrexate oral tablet may cause long-term side effects. These can occur if you take the drug for a long time. Or they may last for a while after you’ve stopped taking the drug.

Examples of long-term side effects reported with methotrexate oral tablet include:

• serious, possibly life threatening infections, including tuberculosis and pneumocystis pneumonia
• severe brain and spinal cord effects, including brain damage
• certain cancers*
• risk of serious side effects†

* To learn more about this side effect, see the “Side effects of methotrexate in detail” section below.
† Methotrexate oral tablet has a boxed warning for this side effect. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). To learn more, see the “Side effects of methotrexate in detail” section below.

Talk with your doctor to learn more about these side effects and how to manage them. Ask your doctor for more information about how long these side effects of methotrexate may last.

Coupon for methotrexate

Visit this page to access Optum Perks coupons and get price estimates for methotrexate when you use the coupons. These coupons can provide significant savings on your prescription costs. 

Note: Optum Perks coupons cannot be used with insurance copays or benefits.

Side effects of methotrexate in detail

Below you’ll find details on some of the side effects of methotrexate oral tablet.

Risk of serious allergic reaction

In studies, serious allergic reactions were rare in people taking methotrexate oral tablet. These reports include cases of anaphylaxis and anaphylactic shock, which are life threatening allergic reactions requiring immediate treatment.

Symptoms of a serious allergic reaction may include:

• skin rash or flushing (temporary warmth, redness, or deepening of skin color)
• swelling under the skin, usually affecting eyelids, lips, hands, or feet
• swelling of the mouth, tongue, or throat, which can make it hard to breathe
• wheezing and difficulty swallowing
• fast, slow, or irregular heart rate

These reactions can also include serious, life threatening skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Symptoms of these reactions may include blistering, red, or discolored skin rashes that cause the skin to loosen and peel.

Ways to manage

Serious allergic reactions caused by methotrexate are life threatening emergencies requiring immediate treatment, such as at a hospital or emergency room. Call 911 or seek immediate treatment if you develop symptoms of a serious allergic reaction. Your doctor will likely recommend that you stop methotrexate treatment if you experience a serious allergic reaction from taking it.

Risk of serious side effects

In studies, serious side effects were rare in people taking methotrexate oral tablet.

Methotrexate may cause serious side effects that can be life threatening, and they include:

• blood cell problems, including severe low white blood cell count
• digestive system problems, including holes in your stomach
• kidney problems, including kidney failure
• liver problems, including liver failure
• lung problems, including severe scarring and inflammation in your lungs
• serious allergic skin reactions, including Stevens-Johnson syndrome 

Ways to manage

If you feel you’re having serious side effects when taking methotrexate oral tablet, immediately tell your doctor. They’ll likely recommend temporarily or permanently stopping treatment with methotrexate. Depending on your specific symptoms, they can also suggest treatment as appropriate.

If your symptoms feel life threatening, seek immediate treatment by calling 911 or going to the closest emergency room.

Certain cancers

In studies, certain cancers were rare in people taking methotrexate oral tablet. These side effects are serious. These cancers include skin cancer and lymphoproliferative disorders such as new cases of leukemia or lymphoma.

Symptoms of skin cancer include unusual new skin growths, such as a discolored mole with uneven or ragged edges.

Symptoms of lymphoproliferative disorders can vary based on the type, but some general ones include:

• swelling of your lymph glands
• sore throat
• unintentional weight loss
• night sweats

Certain factors can increase the risk of certain cancers with methotrexate oral tablet. These factors include too much sun exposure. They may also include receiving treatment with the drug cyclosporine after using methotrexate to treat psoriasis.

Ways to manage

If you experience symptoms of certain cancers listed above, tell your doctor. They’ll likely recommend further testing to evaluate your symptoms and determine possible causes.

Your doctor will likely recommend stopping treatment with methotrexate if they confirm you’ve developed a new cancer while taking the medication. In some cases, lymphoproliferative disorders caused by methotrexate go away once treatment with the drug is stopped.

Allergic reaction

For some people, methotrexate oral tablet can cause an allergic reaction. Methotrexate has a boxed warning for serious allergic reactions. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). To learn more, see the “Side effects of methotrexate in detail” section above.

Symptoms can be mild or serious, and they may include:

• itchiness
• skin rash
• swelling under the skin, usually affecting eyelids, lips, hands, or feet
• swelling of the mouth, tongue, or throat, which can make it hard to breathe
• flushing (temporary warmth, redness, or deepening of skin color)

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 taking the medication.

For severe allergic reaction symptoms, call 911 or your local emergency number right away. To learn more about what to do for a severe reaction, see the “Side effects of methotrexate in detail” section above.

Warnings for methotrexate

Below are some factors you may want to discuss with your doctor before taking methotrexate oral tablet.

Boxed warnings

Methotrexate has boxed warnings about the following risks. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

• risk of harm to the embryo or fetus, including fetal death
• risk of serious allergic reaction, including anaphylaxis
• risk of serious side effects

For details about risk of serious allergic reaction and risk of serious side effects, see the “Side effects of methotrexate in detail” section above. For more information about risk of fetal harm, see the “Methotrexate and pregnancy” section below.

Other warnings

It may not be safe for you to take methotrexate oral tablet if you have specific health conditions. These are sometimes called drug-condition interactions. Other things may also affect whether methotrexate oral tablet is a safe treatment option for you.

Before taking methotrexate oral tablet, tell your doctor about your health and medications you take. Things to consider include:

• kidney conditions
• liver conditions, including ascites
• lung or breathing conditions
• peptic ulcer disease
• ulcerative colitis
• past allergic reaction to methotrexate

Methotrexate and pregnancy

Methotrexate oral tablet should not be taken during pregnancy. If you’re planning a pregnancy or can become pregnant, talk with your doctor before using this medication. Your doctor may suggest birth control options to use during treatment with methotrexate.

Risk of harm to the embryo or fetus

Methotrexate oral tablet has a boxed warning for the risk of harm to the embryo or fetus. A boxed warning is the most serious warning from the FDA.

Studies have shown that methotrexate can cause harm to the embryo or fetus, including death of the fetus, if used during pregnancy.

Because of this risk, doctors will suggest using effective birth control during treatment and for at least 6 months after your last dose if you can become pregnant. And if you’re a male* taking methotrexate and have a sexual partner who can become pregnant, you’ll need to use birth control (such as condoms) during treatment and for at least 3 months following your last methotrexate dose.

Talk with your doctor if you’d like to learn more about possible treatments for your condition that may be safer to use during pregnancy.

* Sex and gender exist on spectrums. In this article, we use the term “male” to refer to a person’s sex assigned at birth.

Methotrexate and breastfeeding

Methotrexate oral tablet should not be used while breastfeeding. Also, do not breastfeed for at least 1 week after your last dose. If you’re currently breastfeeding or planning to do so, talk with your doctor before taking this medication.

Methotrexate and alcohol

Methotrexate oral tablet is known to interact with alcohol.

It may be best to minimize or avoid alcohol consumption while taking methotrexate. Rarely, methotrexate can cause liver damage, which can be life threatening. Drinking alcohol further raises the risk of this side effect.

If you drink alcohol, talk with your doctor about whether it’s safe to consume it during your treatment with methotrexate oral tablet.

What to ask your doctor

This article describes common and serious side effects of methotrexate oral tablet. If your doctor prescribes this medication, they can discuss possible side effects with you. Let your doctor know if you have concerns or questions about treatment with this medication.

Here’s a list of some possible questions you may want to ask your doctor:

• How do side effects of methotrexate compare with those of other treatments for my condition?
• Does my health history raise my risk of side effects if I take methotrexate?
• Do any medications I take interact with methotrexate and increase my risk of side effects?
• Does my risk of side effects from taking methotrexate depend on the condition I’m taking it for?

Disclaimer: Optum Perks 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.