Methotrexate (Trexall) belongs to a drug class called antimetabolites. It’s used as chemotherapy at high doses to kill cancer cells and treat different cancers, such as acute lymphoblastic leukemia (ALL). At lower doses, methotrexate (Trexall) is considered a disease-modifying antirheumatic drug (DMARD) that treats certain non-cancer conditions, such as rheumatoid arthritis (RA). This medication is a tablet that you take by mouth. For most conditions, it’s taken once a week, but for some, it’s taken more often than that. Methotrexate (Trexall) side effects include mouth sores, nausea, and stomach upset.
Cancer:
Acute lymphoblastic leukemia (ALL) in adults and children; given with other chemotherapy
Cutaneous T-cell lymphoma in adults; given by itself or with other chemotherapy
Advanced non-Hodgkin lymphoma in adults; given with other chemotherapy
Non-cancer conditions:
Rheumatoid arthritis (RA) in adults
Polyarticular juvenile idiopathic arthritis (pJIA) in children
Severe psoriasis in adults
Methotrexate (Trexall) is an antimetabolite medication that treats many types of cancers and non-cancer conditions (like arthritis and psoriasis).
For cancer: Methotrexate (Trexall) works by blocking dihydrofolate reductase, a protein in your body that’s important for making DNA in cells and for cell growth. Since cancer cells grow much more quickly than healthy cells, the medication helps slow down cancer growth so the cancer can’t spread as well.
For non-cancer conditions: We don’t know exactly how methotrexate (Trexall) works to treat non-cancer conditions such as rheumatoid arthritis and psoriasis. But research suggests that, at lower doses, it blocks the immune system from becoming too active. For psoriasis, the medication might also help slow down the growth of skin cells.
Source: DailyMed
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
Black, tarry stools
bleeding gums
blood in the urine or stools
bloody vomit
increased heartbeat
itching, rash, reddening of the skin
joint pain
pinpoint red spots on the skin
sores in the mouth or lips
stomach pain
swelling of the eyelids, face, lips, hands, feet, or lower legs
swelling or inflammation of the mouth
trouble breathing
unusual bleeding or bruising
vomiting
yellow eyes or skin
Less common
Back pain
bloody nose
blurred vision
body and muscle pain
burning while urinating
confusion
continuing ringing, buzzing, or other unexplained noise in the ears
cough or hoarseness
cracked, dry, scaly skin
dark urine
dizziness
drowsiness
ear congestion
fever or chills
headache
loss of appetite
loss of hearing
loss of voice
lower back or side pain
painful or difficult urination
pale skin
seizures
stuffy or runny nose
unusual tiredness or weakness
white or brownish vaginal discharge
Incidence not known
blistering, peeling, or loosening of the skin
blurred or change in vision
changes in skin color
confusion
decreased interest in sexual intercourse
difficulty in moving
dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
dryness or soreness of throat
fruit-like breath odor
inability to have or keep an erection
increased hunger or thirst
indigestion
irritation in the mouth
large, flat, blue, or purplish patches in the skin
loss in sexual ability, desire, drive, or performance
loss of consciousness
menstrual problem
night blindness
pain in the chest or groin
pain, redness, swelling, or tenderness in the arm or leg
red skin lesions, often with a purple center
red, wart-like spots on the skin
sudden loss of coordination
sudden onset of slurred speech
swelling or soreness of the breasts
swollen, painful, or tender lymph glands in the neck or armpit
tingling or numbness in the hands, feet, or lips
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
Hair loss or thinning
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Taken by mouth, so a good option for people who don’t like needles
A non-steroidal option for autoimmune conditions (e.g., rheumatoid arthritis, psoriasis)
Doesn’t typically cause hair loss or weight gain
Might cause nausea and mouth sores
Can raise your risk for infection
Requires regular office visits and lab tests to check for serious side effects
Make sure you take methotrexate (Trexall) only at the dose that your provider prescribed for your specific medical condition. The dose is very different for cancer and non-cancer conditions. Ask your provider if you’re not sure what your dose is.
Follow your provider’s instructions to get any lab tests or scans done during your treatment with methotrexate (Trexall). These tests help your provider make sure that the medication is safe for you.
If you’re taking methotrexate (Trexall) for a non-cancer condition (such as rheumatoid arthritis), your provider will recommend that you take folic acid supplements to help prevent side effects.
If you’re taking methotrexate (Trexall) to treat cancer, check your temperature often. Contact your provider as soon as possible if you have a fever (a temperature that’s 100.4 degrees Fahrenheit or higher). It’s important for your provider to know if you get sick. Sometimes, a fever might be the only sign that you’re sick.
Don’t start or stop any new medications without talking to your provider or pharmacist first. There are several medications that can raise your risk for side effects when they’re taken with methotrexate (Trexall). Your care team should check to make sure all your medications are safe for you to take.
Before you get any vaccines, tell your provider or pharmacist that you’re taking methotrexate (Trexall). Some vaccines might not work well for you during treatment. Be sure to avoid getting live vaccines because of the risk of infection from the vaccine itself. Your provider can check that you can get the vaccine that you’re interested in.
It’s not recommend to breastfeed while you’re taking methotrexate (Trexall) and for 1 week after your last dose. We don’t know whether the medication passes into human milk. But because of the way methotrexate (Trexall) works, it could harm a breastfed infant.
Store methotrexate (Trexall) tablets at room temperature. Keep the medication in the same bottle you got from the pharmacy or provider’s office, unless your provider tells you differently.
Ask your provider about the best way to handle methotrexate (Trexall) safely. Because this medication is sometimes used for treating cancer, it can be harmful to people who handle or come in contact with them. Keep it in a safe place away from children and pets.
If you have leftover medication, ask your provider about how to get rid of it. You might be able to bring it to the provider’s office or clinic for proper disposal.
Methotrexate (Trexall) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Methotrexate (Trexall) can cause harm to an unborn baby and pregnancy loss (miscarriage) when it’s taken during pregnancy. For this reason, you can’t take this medication for non-cancer conditions if you’re pregnant.
In general, it’s best to avoid becoming pregnant while you’re taking methotrexate (Trexall). If you or your partner can become pregnant, you should use reliable birth control while you’re taking methotrexate (Trexall). Keep using birth control for 6 months after the last dose (for females) or for 3 months after the last dose (for males). Contact your provider right away if you or your partner gets pregnant during treatment.
Some people have experienced allergic reactions to methotrexate (Trexall). Let your nurse or provider know right away if you have any symptoms of a reaction such as itching, fever, nausea, trouble breathing, or a fast heartbeat. Get medical help as soon as possible if you have an anaphylactic reaction, such as hives, swelling in the face or lips, or throat tightness.
Methotrexate (Trexall) can cause low blood cell counts, particularly in people taking the medication at doses for cancer treatment. When your red blood cells are low, you might feel more tired. And when your platelets are low, you’re at risk for bleeding. In addition, low white blood cells put you at risk for serious and life-threatening infections.
Your provider will check your blood cell counts before you start methotrexate (Trexall) and every so often during treatment. Your provider will pay close attention to your white blood cell counts. If your counts are too low, your provider might make adjustments to your treatment to give your body time to make new blood cells.
It’s important to lower your risk of getting sick by washing your hands often and avoiding crowds. Check your temperature regularly, and call your provider right away if your temperature is 100.4 degrees Fahrenheit or higher.
Risk factors: Peptic ulcer disease | Ulcerative colitis
Sometimes, methotrexate (Trexall) causes vomiting, diarrhea, mouth sores, stomach bleeding, or tears in the gut. Your provider might recommend antiemetics such as ondansetron (Zofran) to help with nausea or loperamide (Imodium A-D) to treat diarrhea. Seek medical help right away if you have sudden stomach pain or blood in your stool.
Risk factors: Heavy alcohol use
Some people taking methotrexate (Trexall) have developed liver problems, including cirrhosis or liver failure. People who take methotrexate (Trexall) for psoriasis have a higher risk of liver problems the longer they take the medication. Talk to your provider about the benefits and risks of taking this medication if you have liver problems. Your provider will check your liver with lab tests. You might need to pause methotrexate (Trexall) if you have high liver enzyme levels on your test results because this can suggest liver damage.
Some people who’ve taken methotrexate (Trexall) have had a serious lung problem called interstitial lung disease (ILD). Talk to your provider right away if you have a sudden or worsening cough, trouble breathing, and fever. You might have to pause or stop methotrexate (Trexall) while your provider examines your lungs.
Risk factors: Previous radiation | Previous sunburn
Methotrexate (Trexall) can cause serious skin problems, including severe and potentially life-threatening skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN). Tell your provider right away if you start having painful blisters, skin wounds, or peeling skin. These are signs of a serious skin reaction that need immediate medical attention.
Methotrexate (Trexall) might also cause skin burns from being out in direct sunlight or from previous radiation. You should avoid sun exposure when possible. If you’re going outdoors, wear sunscreen with an SPF of at least 30 and clothes that protect your skin. Let your provider know if you get a sunburn or have painful skin while you’re taking methotrexate (Trexall).
Methotrexate (Trexall) can cause kidney damage, sometimes leading to problems like permanent kidney failure. Your provider will closely monitor your kidney health during treatment. You might need to stop taking methotrexate (Trexall) for a while so your provider can look into the problem.
It’s very important that you take the exact dose of methotrexate (Trexall) that your provider prescribes. Otherwise, the medication can cause serious and sometimes life-threatening side effects. Most commonly, these mistakes happen when people take methotrexate (Trexall) once a day when they’re instructed to take it only once per week. Some ways to help you take methotrexate (Trexall) as prescribed is to use a reminder app on your phone or choose day(s) of the week that are easy to remember.
Folic acid, also called folate, is a B vitamin that helps cells grow and make DNA. To treat cancer, methotrexate (Trexall) works by stopping your body from making folate. This lowers the amount of folate in your body, which causes cancer cells to die. Most people who take methotrexate (Trexall) for cancer shouldn’t take folic acid supplements because they can make methotrexate (Trexall) work less well to treat your cancer.
But when methotrexate (Trexall) is taken for autoimmune conditions such as psoriasis, regularly taking folic acid is important for replenishing the important nutrient in your body and preventing certain side effects. Talk to your provider about whether or not you should take folic acid while you’re taking methotrexate (Trexall).
People who take Methotrexate (Trexall) have a higher risk of getting sick, particularly from opportunistic infections (infections that usually only happen when the immune system is weak). Sometimes, providers prescribe additional medications, such as antibiotics and antiviral medications, to prevent infections. Contact your provider right away if you feel sick, such as having a fever, muscle aches, night sweats, severe tiredness, cough, or trouble breathing. You might need to start taking a lower dose or stop methotrexate (Trexall) altogether if you develop a serious infection during treatment.
Risk factors: Previous radiation to the brain
Some people taking methotrexate (Trexall) developed serious nervous system problems including headache, confusion, seizures, difficulty moving one side of the body, vision changes, and coma. Sometimes, the symptoms are temporary and completely go away; other times, they can be permanent. Your provider will regularly perform exams to check your nervous system while you’re taking methotrexate (Trexall). But contact your provider right away if you have any symptoms between office visits.
Some people who took methotrexate (Trexall) have developed new cancers. Some people reported getting cancers that affect their white blood cells (lymphoproliferative disease) even at low doses of methotrexate (Trexall); the new cancer improved when they stopped the medication in these cases. You might be at higher risk for skin cancers if you have psoriasis and you're taking both methotrexate (Trexall) and cyclosporine.
Your provider will check for signs of new cancers from your lab tests and your symptoms during treatment. Speak with your provider if you notice any new, unusual symptoms. If your blood tests are abnormal or if you have symptoms of other cancers, you might need to pause your treatment while your provider looks into it.
Risk factors: Taking methotrexate (Trexall) to treat cancer
Tumor lysis syndrome (TLS) is a complication of treatment if you’re taking methotrexate (Trexall) for cancer. This happens when cancer cells are destroyed and the cells release what they have inside into the bloodstream. This complication can be dangerous because it can lead to high levels of uric acid and potassium in the blood, which can cause kidney or heart problems.
Your provider might give you extra fluids to prevent TLS. Your provider will also check your electrolyte levels often. If your lab results show signs of TLS, you might need to pause methotrexate (Trexall) while you get treated for this complication.
Methotrexate (Trexall) might cause infertility, which means you might not be able to have children in the future. People have reported low sperm count and menstrual problems. It’s unclear whether these changes are reversible. Talk to your provider about your options for fertility preservation if you’re considering having children in the future.
Risk factors: Fluid buildup in the stomach area or lungs
Methotrexate (Trexall) can build up in pockets of fluid in the body. The medication can stay in your body longer if you’ve been told that you have fluid buildup in your body, such as around your stomach (ascites) or your lungs. This can put you at risk for worse side effects from methotrexate (Trexall). Your provider will check for any extra fluid in your body and manage or treat it before you start methotrexate (Trexall).
The dose of methotrexate (Trexall) varies depending on what condition you’re taking the medication for. Sometimes, the dose depends on your body size or body surface area (BSA) in m2 units.
The manufacturer dosages are listed below, but your dose might be different depending on the specific guidelines that your provider uses. Your provider might adjust the dose based on your response to methotrexate (Trexall).
Cancer
Acute lymphoblastic leukemia: The typical starting dose is 20 mg/m2 by mouth once a week. Methotrexate (Trexall) is taken together with other chemotherapy.
Mycosis fungoides: When taken by itself, the typical dose of methotrexate (Trexall) is 25 mg to 75 mg by mouth once a week. When it’s taken with other chemotherapy, the typical dose of methotrexate (Trexall) is 10 mg/m2 by mouth twice a week.
Non-Hodgkin lymphoma: The typical dose is 2.5 mg by mouth 2 to 4 times per week, taken together with chemotherapy.
Non-cancer conditions
Rheumatoid arthritis: The typical starting dose is 7.5 mg by mouth once a week.
Polyarticular juvenile idiopathic arthritis: The typical starting dose is 10 mg/m2 by mouth once per week.
Psoriasis: The typical dose is 10 mg to 25 mg by mouth once a week.
For non-cancer conditions, methotrexate (Trexall) is commonly taken with folic acid supplements to help lower the risk for side effects.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
History of severe allergic reaction to methotrexate
Currently pregnant (only if taking for non-cancer conditions)
Cancer:
Acute lymphoblastic leukemia (ALL) in adults and children; given with other chemotherapy
Cutaneous T-cell lymphoma in adults; given by itself or with other chemotherapy
Advanced non-Hodgkin lymphoma in adults; given with other chemotherapy
Non-cancer conditions:
Rheumatoid arthritis (RA) in adults
Polyarticular juvenile idiopathic arthritis (pJIA) in children
Severe psoriasis in adults
Uncomplicated malaria in adults and children
Rheumatoid arthritis (RA) in adults
Systemic lupus erythematosus (SLE) in adults
Discoid lupus erythematosus (DLE) in adults
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