- Methotrexate Print Page
- Psoriasis treatment: Methotrexate
- Why do dermatologists prescribe methotrexate to treat psoriasis?
- Safety and effectiveness
- How to take methotrexate
- Possible side effects
- What to discus with your dermatologist
- The Facts on Methotrexate for Rheumatoid Arthritis Treatment
- How Methotrexate Helps Ease Inflammation
- What is methotrexate?
- Important Information
- Before taking this medicine
- How should I take methotrexate?
- What happens if I miss a dose?
- What happens if I overdose?
- What should I avoid while taking methotrexate?
- Methotrexate side effects
- What other drugs will affect methotrexate?
- Further information
- More about methotrexate
- 11 Common Questions About Taking Methotrexate for Rheumatoid Arthritis
- 1. How does methotrexate work? Is it a pain pill?
- 2. Is methotrexate a cancer drug? Why am I taking a pill for cancer?
- 3. What’s the difference between taking methotrexate pills and getting shots?
- 4. How long will methotrexate take to start working?
- 5. Why do I have to take folic acid? Should I take it on the same day as MTX or not?
- 6. What are the worst side effects of methotrexate? Is my hair going to fall out?
- 7. Can I get pregnant or breastfeed while taking methotrexate?
- 8. Can I drink alcohol while taking methotrexate?
- 9. Will methotrexate mess up my immune system?
- 10. What about getting vaccines while on methotrexate?
- 11. Will I ever need to take biologics?
- Keep Reading
- Methotrexate for RA: A ‘fascinating drug’
- Enhancing effectiveness of biologics
- Side effects of methotrexate
Methotrexate Print Page
What is methotrexate?
- Methotrexate is in a class of medications called Disease Modifying Anti-Rheumatic Drugs, or DMARDs.
- DMARDs are a slow acting but effective treatment for rheumatoid arthritis and other form of inflammatory arthritis.
- Methotrexate is considered the current gold standard first line treatment for rheumatoid arthritis because of its effectiveness and side effect profile.
- It is also used in the treatment of other types of inflammatory arthritis, lupus, vasculitis, myositis and others.
What is the typical dose for methotrexate?
- Most rheumatologists will dose methotrexate between 15mg and 25mg.
- In some cases, the dose may be higher or lower based on the condition being treated and other factors related to the individual patient’s disease or other medical conditions.
- It is only taken one day per week.
- Methotrexate can be administered in 2 forms:
- 2.5mg tablets (6-10 tablets/week)
- An injection underneath the skin (similar to an insulin shot)
How does methotrexate work?
- While there has been extensive research into this area, it remains unclear as to the exact mechanism of action. Methotrexate is an anti-folate drug, and it also has many different specific effects which modulate the body’s immune system.
- Like all DMARDs, Methotrexate takes time to work. Most patients start to feel the positive effects of methotrexate at 4-8 weeks, with maximum benefit at 3-6 months. Side effects can occur earlier.
What is the difference between taking methotrexate tablets versus the injection?
- There is good evidence that injectable methotrexate is more reliably effective than tablets, particularly as the dose increases. The risk of some side effects may also be less compared to the tablet form. Isn’t methotrexate used to treat cancer? Has my doctor not told me I have cancer?
- While methotrexate is used in the treatment of cancer, its frequency and dosing is much higher. When used in the treatment of a rheumatic condition, methotrexate is considered to be a relatively low dose and would not be used that way to treat cancer.
If methotrexate is the gold standard treatment, why am I on more than just methotrexate?
- For rheumatoid arthritis and other types of inflammatory arthritis, there is some evidence that treatment is more effective when DMARDs are combined together. Even the newer biologics work better in combination.
What are the possible side effects of methotrexate?
|Side Effect||Ways to Reduce Side Effects|
|Methotrexate can cause gastrointestinal upset, fatigue, or even flu-like symptoms in some people. If it occurs, it is usually the day or two after you have taken your methotrexate.||
|Methotrexate can cause painful sores
in the mouth.
|Methotrexate can decrease your blood counts and/or irritate your liver||
|Effect on the kidneys||
|Methotrexate can cause inflammation or even scarring in the lungs||
|Pregnancy miscarriages or malformations||
|Risk of Cancer||
What should I do if I miss a dose?
- If you miss your dose, you can take it the next day safely. Then, resume your normal weekly routine. If it has been more than 1-2 days, wait until your next weekly scheduled dose. As long as this does not happen regularly, you will likely not feel any ill effects.
How can I safely stop methotrexate?
- It is safe to just stop methotrexate; you do not need to slowly reduce the dose. However, keep in mind, if you were gaining any benefit from methotrexate, it will usually take at least 6 weeks to lose it.
For more information about methotrexate, or for questions that are specific to your situation, always consult your physician.
Psoriasis treatment: Methotrexate
Methotrexate is a strong medicine. The US Food and Drug Administration (FDA) approved it to treat adults with severe, disabling psoriasis that cannot be controlled with medicine applied to the skin or light treatments. Methotrexate works by suppressing the overactive immune system that causes psoriasis.
Why do dermatologists prescribe methotrexate to treat psoriasis?
This prescription medicine can treat:
Severe and disabling psoriasis
Your dermatologist may tell you to stop drinking alcohol while taking methotrexate. This can reduce problems with your liver.
Safety and effectiveness
Methotrexate can effectively treat severe psoriasis, psoriatic arthritis, and nail psoriasis. Most patients see less psoriasis in four to six weeks. It may take six months to get complete clearing. While it can be very effective, no treatment works for everyone. For some people, adding another treatment can deliver the best possible results. Before you can take methotrexate, your dermatologist will carefully evaluate you to decide if you can take it. Be sure to tell your dermatologist about:
All medicines that you are taking, including ones that you can buy without a prescription such as ibuprofen (Advil, Motrin) and naproxen (Aleve)
Diseases that you have and ones that run in your family
How much alcohol you drink
If you are pregnant or want to become pregnant
Pregnancy: Women who are pregnant or planning to become pregnant should NOT take methotrexate. This medicine can cause miscarriages and serious birth defects.
Stop methotrexate before getting pregnant
Want to have a child? Both men and women who take methotrexate should stop taking this medicine and wait at least 3 months before trying to have a child.
Breastfeeding: Women who are breastfeeding should NOT take methotrexate. Children: Methotrexate is FDA-approved to treat adults with severe psoriasis. The FDA has also approved it to treat children with juvenile rheumatoid arthritis, so we know a bit about how this medicine works in children. In general, children tend to do well on this medicine and have fewer side effects. Children take methotrexate for the shortest possible time, and dermatologists tend to prescribe the lowest possible dose. To get the best possible results while treating psoriasis, a dermatologist may add another treatment to a child’s treatment plan. If your dermatologist says that methotrexate may be a medicine you can take, you’ll need to have some medical tests first, such as blood work. You’ll also need a tuberculosis (TB) test. While taking methotrexate, you’ll need blood tests to see if the medicine is affecting your liver.
Methotrexate and the sun
When taking methotrexate, you should:
Protect your skin from sunlight
NOT use sunlamps or tanning beds.
Sun protection will help prevent sunburn and psoriasis flares.
How to take methotrexate
Methotrexate comes in many forms. You may be prescribed a pill or liquid. Some patients inject methotrexate at home. Each form has benefits. For example, injecting methotrexate can reduce side effects such as nausea and vomiting.
Before taking methotrexate for the first time, be sure to carefully read the instructions. If the instructions are confusing or differ from what your dermatologist said, call your dermatologist before taking methotrexate. Some patients stay on methotrexate for a long time. Others stop taking methotrexate once their psoriasis is under control and restart when psoriasis flares.
Follow recommended dosage
Most people take methotrexate once a week. Taking it more often than your dermatologist prescribes can cause serious health problems.
Possible side effects
Methotrexate can cause many possible side effects, so dermatologists carefully monitor each patient. Vomiting, nausea, loss of appetite, mouth sores, redness and swelling inside the mouth, and fatigue are common side effects. If you experience any of these side effects, tell your dermatologist immediately. Your dermatologist may be able to control these side effects by changing how you take methotrexate or adding a folic acid (a type of B vitamin) supplement to your treatment plan. More-serious side effects are also possible. Methotrexate can reduce your body’s ability to fight infections. It can also have serious effects on your liver, lungs, or kidneys. When found early, these side effects can often be stopped, so it’s important to:
Immediately tell your dermatologist about any side effects
Get all of the medical tests that your dermatologist requires
To check for liver problems and other side effects, you will need to have blood tests. When you start taking methotrexate, you may need to get a blood test every two to four weeks for a few months. Then, you’ll likely need a blood test every one to three months. If a test result shows a problem, you may need to stop taking methotrexate.
What to discus with your dermatologist
Be sure to tell your dermatologist if you:
Experience any health problem, even if it seems unrelated to taking methotrexate, such as fever, chills, body aches, bleeding, or bruising easily
Feel uncertain about how to (or how often to) take methotrexate
Think the information that came with the medicine about how to take methotrexate differs from what your dermatologist told you
Cordoro KM. “Management of childhood psoriasis.” Adv Dermatol. 2008;24:125-69.
Feldman SR. “Treatment of psoriasis.” UpToDate 2015 Jul, Wolters Kluwer Health. Last accessed November 2015.
Hugh J, Van Voorhees AS, et al. “From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies.” J Am Acad Dermatol. 2014;70:168-77.
Marks, B. “More than skin deep: Triggers, treatments, and you.” An educational session hosted by the National Psoriasis Foundation. Chicago: Presented June 20, 2015.
Menter A, Korman NJ, et al. “Guidelines of care for the management of psoriasis and psoriatic arthritis Section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents.” J Am Acad Dermatol2009;61:451-85.
All content solely developed by the American Academy of Dermatology
Supported in part by Novartis.
Asked by AmyAria
How Long Will Methotrexate Fatigue Last?
I’ve taken methotrexate for two weeks and it wipes me out!! I can handle a day or two a week of this for the “greater good” and all, but then I just got stuff I have to do!! I’m not completely incapacitated, but I am getting really tired of my husband’s cooking…God bless him! I even find myself pining to do the stuff I used to complain about doing! Will the fatigue gradually get better as my body acclimates?
Oh the fatigue. I deal with it too on a weekly basis. Methotrexate can cause severe fatigue, but there are good news. Slowly but surely the methotrexate will build up in your body and your side effects will become less severe. I can’t promise you that the fatigue will go away. It does for some, but others can be on methotrexate for years and still experience fatigue. That said, one of the first signs of a medication working can be having more energy. This means that although you may experience a fatigue for a few days after you take your medication, you may end up having more energy the rest of the time.
RA and fatigue go hand in hand. In fact, people with RA have a higher need for sleep and when your disease is more active, it’s common to be more tired. Have you heard of the Spoon Theory? It’s a way of explaining how people with chronic illness often have to be more cautious about how they use their energy. You may want to read our tips on managing energy levels with RA.
There are ways of managing side effects from medication, including fatigue. You may want to talk to your rheumatologist about your fatigue. Sometimes getting a prescription of folic acid can help reduce it. Other tips include scheduling your meds for the day before the weekend allows you to take it easy and give your body the rest of needs. Sleep in, try to have low-key days, nap when you need it. When you and your husband cook, make more than you need for one day, put it in the freezer, so you have food to warm up when you’re not up for doing much.
I completely understand the anxiety of not being able to get up and do what needs to be done. I’ve developed some tricks that can help, even on your tired days. I make a list of things that need to be done throughout the week. Instead of overdoing it before I take my methotrexate (which makes the fatigue even more severe), I try to distribute the chores out throughout the week. Say there are 5 important chores that need to be done throughout the weekdays. Instead of doing two or three of them the days before you take you methotrexate (as we tend to do because we know the fatigue will knock us out) do one chore a day, even on the day you take your methotrexate. If you can’t accomplish it, then put it on the list for either the weekend or the next week. You will find that it you don’t overdo it before and after you take the methotrexate the fatigue won’t be near as bad.
I hope this helps. Good luck and best wishes!
The Facts on Methotrexate for Rheumatoid Arthritis Treatment
For people who have more than mild symptoms of rheumatoid arthritis, or RA, methotrexate (Rheumatrex, Trexall) is one of the most commonly prescribed drugs. It’s a leader in a class of drugs known as DMARDs – for disease-modifying anti-rheumatic drug – and it works to slow the progression of joint damage from the disease.
How Methotrexate Helps Ease Inflammation
Methotrexate works by reducing the function of the cells that are causing inflammation in the joint tissues. “Its use can reduce inflammation and therefore should help relieve pain and protect from joint damage,” notes Sean A. Whelton, MD, a rheumatologist and associate professor of medicine at MedStar Georgetown University Hospital in Washington, D.C. Less inflammation in the joints should mean less joint pain and less joint swelling. You should also feel less fatigue and less morning stiffness.
People with swollen and painful joints whose rheumatoid arthritis has not improved with initial, non-drug therapies will most likely be prescribed methotrexate for RA management. But it may take weeks to several months until the full benefits of methotrexate are noticeable, says Barbara Young, PharmD, MHA, editor of consumer medication information for the American Society of Health-System Pharmacists in Bethesda, Maryland. While you’re waiting for the effects to start, you may be given other medications, such as corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), to help you manage your RA symptoms.
The goal is to feel more and more improvement over a few months, reaching a level of stabilization after four to six months. But methotrexate doesn’t work for everyone. The drug is a slow but steady process, taking about 5 to 6 weeks to start working, says Dr. Whelton. “I find about half of people will experience relief with methotrexate alone, while the other portion usually adds other medications to treat their RA.”
According to a research review, published in January 2013 in the journal BMC Medicine, that analyzed predictors for methotrexate success, men respond better than women, non-smokers respond better than smokers, and people who take methotrexate as their first DMARD do better than people who have already tried another drug in this category. The review also found that those who take methotrexate in an early and mild stage of RA do better than those who start the drug after they have had RA for a long time. The researchers point out that if doctors can identify who is unlikely to respond to methotrexate, those patients can be spared exposure to a potentially toxic drug.
If you do not have a significant improvement in joint inflammation and well-being after about three months of RA treatment, your doctor will probably consider adding another drug to your treatment, especially a biologic drug such as etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade). The treatment goal is to achieve early, complete (or near complete) control of joint inflammation so there’s less risk for long-term damage to the joints over the years.
Methotrexate is one of the most effective and widely used medications for treating inflammatory types of arthritis. It’s also one of the safest arthritis drugs, despite a common misconception among many patients that methotrexate is highly toxic.
Confusion about this medication’s safety seems to exist because it is also used – in much higher doses – for treating some forms of cancer. Most people who use methotrexate to treat their inflammatory arthritis take between 10 and 25 mg per week. By contrast, the doses used to treat leukemia and other types of cancer may be hundreds of times larger.
That’s not to suggest that taking methotrexate is risk-free. But doctors who prescribe methotrexate for arthritis say that following a few simple steps can make it even safer to use and reduce potential side effects.
How Methotrexate Works
Understanding how methotrexate works helps explain why it can cause unwanted effects. Originally developed as a cancer drug, methotrexate stops cancerous cells from rapidly multiplying and spreading by blocking their access to folate, a form of vitamin B. Unfortunately, depleting the body of folate can affect healthy cells, too, especially those in the gastrointestinal (GI) tract, mouth and hair follicles.
Blocking folate fights cancer, but that’s not why it helps arthritis. Researchers believe that methotrexate slows the progression of RA and relieves symptoms by causing cells to release a molecule called adenosine, which blocks other chemicals that promote inflammation, explains Edwin Chan, MD, a rheumatologist and researcher at the New York University School of Medicine. This happens unrelated to folate.
Common Side Effects
GI problems such as nausea and vomiting are the most common side effects associated with methotrexate, affecting between 20 and 65 percent of RA patients who take the drug. Up to one third develop mouth ulcers or sores. Many also complain of headaches, fatigue and an overall “blah” feeling. This is sometimes called “methotrexate fog,” and can occur a day after receiving a dose of methotrexate (which is taken in pill form or injected once a week). Hair loss is a relatively uncommon side effect in people who take methotrexate at arthritis-relieving doses.
Side Effects Prevention Tips
The good news: These common side effects can often be short-circuited by taking a folic acid supplement. Folic acid is the synthetic form of folate. One study found that rheumatoid arthritis (RA) patients on methotrexate who took folic acid supplements lowered the risk of GI problems and mouth sores by 79 percent.
Ask your doctor for complete instructions for using folic acid supplements because dosages and when you take them can vary. Some physicians recommend taking 1 mg of folic acid daily, whereas others instruct patients to pop a single 5-mg dose once a week. You may also be told to take folic acid 24 hours after receiving a dose of methotrexate.
A few additional steps may help prevent or relieve GI and oral problems:
Split the dose. Most arthritis patients take methotrexate orally, in a dose consisting of several pills. Some find that splitting the dose eases GI side effects. Take half the pills in the morning and the other half 12 hours later, preferably with food.
Ask about anti-nausea medication. For very severe stomach upset, your doctor can prescribe an anti-nausea drug such as ondansetron (Zofran).
Switch to injections. When nothing else helps, switching from oral methotrexate to the injectable version can eliminate GI distress.
Try a rinse. To relieve painful mouth sores, a salt-water rinse or special mouthwash containing lidocaine (a pain reliever) may help.
Protect the Liver
Releasing adenosine may fight inflammation and help relieve painful, swollen joints. But Dr. Chan notes that adenosine also causes fibrosis, or buildup of scar tissue, in the liver. Over time, that could result in liver disease. To monitor and limit your risks, your doctor may recommend you avoid alcohol and will run routine blood tests to monitor your liver function. Keep in mind that only about one in 1,000 patients with RA who are taking methotrexate experience serious liver damage.
Watch for Other Complications
Methotrexate users may develop other issues, but many can be monitored by regular blood tests. These side effects often go away if you stop taking the drug temporarily (which should only be done under a doctor’s supervision). Risks and side effects to be aware of:
Fibrosis and inflammation in the lungs. If you do have a dry cough, shortness of breath, or any other respiratory problems, make sure to tell your doctor.
A drop in white blood cells, which could cause infections.
A dip in production of blood platelets, which could cause abnormal bleeding.
You may be wary of side effects with methotrexate, but most people tolerate the drug quite well, especially if they take folic acid, follow doctors instructions and practice other good health habits.
Methotrexate Side Effect Stats
Percent of people taking methotrexate with GI problems such as nausea and vomiting.
Percent of RA patients on methotrexate who took folic acid supplements and lowered the risk of GI problems and mouth sores.
Percent of patients on long-term methotrexate therapy who experiece elevations in liver tests. These increases are usually mild and resolve without treatment.
Generic Name: methotrexate (oral) (meth oh TREX ate)
Brand Names: Otrexup, Rasuvo, Rheumatrex Dose Pack, Trexall, Xatmep
Medically reviewed by Sophia Entringer, PharmD Last updated on Jan 5, 2019.
- Side Effects
What is methotrexate?
Methotrexate interferes with the growth of certain cells of the body, especially cells that reproduce quickly, such as cancer cells, bone marrow cells, and skin cells.
Methotrexate is used to treat certain types of cancer of the breast, skin, head and neck, or lung. It is also used to treat severe psoriasis and and certain forms of rheumatoid arthritis.
Methotrexate is usually given after other medications have been tried without successful treatment of symptoms.
Methotrexate made also be used for purposes not listed in this medication guide.
Methotrexate is usually not taken every day. You must use the correct dose for your condition. Some people have died after taking methotrexate every day by accident.
Do not use methotrexate to treat psoriasis or rheumatoid arthritis if you have low blood cell counts, a bone marrow disorder, weak immune system, liver disease (especially if caused by alcoholism), or if you are pregnant or breast-feeding.
Methotrexate can cause serious or life-threatening side effects. Tell your doctor if you have diarrhea, mouth sores, cough, shortness of breath, upper stomach pain, dark urine, numbness or tingling, muscle weakness, confusion, seizure, or skin rash that spreads and causes blistering and peeling.
Call your doctor if you have unusual bruising or bleeding, or signs of infection (fever, chills, body aches).
Do not use methotrexate if you are pregnant or breast-feeding a baby.
Before taking this medicine
You should not use methotrexate if you are allergic to it. Methotrexate should not be used to treat psoriasis or rheumatoid arthritis if you have:
alcoholism, cirrhosis, or chronic liver disease;
low blood cell counts;
a weak immune system or bone marrow disorder; or
if you are pregnant or breast-feeding.
Methotrexate is sometimes used to treat cancer even when patients do have one of the conditions listed above. Your doctor will decide if this treatment is right for you.
Tell your doctor if you have:
any type of infection; or
Methotrexate can harm an unborn baby or cause birth defects, whether the mother or father is taking this medicine.
If you are a woman, do not use methotrexate to treat psoriasis or rheumatoid arthritis if you are pregnant. You may need to have a negative pregnancy test before starting this treatment. Use an effective form of birth control while you are taking this medicine, and for 6 months after your last dose.
If you are a man, use a condom to keep from causing a pregnancy while you are using methotrexate. Continue using condoms for at least 3 months after your last dose.
Tell your doctor right away if a pregnancy occurs while either the mother or the father is taking methotrexate.
This medicine may affect fertility (ability to have children) in both men and women. However, it is important to use birth control to prevent pregnancy because methotrexate may harm the baby if a pregnancy does occur.
You should not breast-feed while using this medicine.
Do not give this medicine to a child without the advice of a doctor.
How should I take methotrexate?
Take methotrexate exactly as it was prescribed for you. Follow all directions on your prescription label and read all medication guides or instruction sheets.
Methotrexate is sometimes taken once or twice per week and not every day. You must use the correct dose. Some people have died after taking methotrexate every day by accident. Ask your doctor or pharmacist if you have questions about your dose or how often to take it.
Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).
Methotrexate can be toxic to your organs, and may lower your blood cell counts. Your blood will need to be tested often, and you may need an occasional liver biopsy. Your cancer treatments may be delayed based on the results.
If you need to be sedated for dental work, tell your dentist you currently use this medicine.
Store tablets at room temperature away from moisture and heat.
Store the liquid medicine in the refrigerator, do not freeze.
You may also store the liquid at room temperature for up to 60 days.
What happens if I miss a dose?
Call your doctor for instructions if you miss a dose of methotrexate.
Get your prescription refilled before you run out of medicine completely.
What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of methotrexate can be fatal.
What should I avoid while taking methotrexate?
Avoid drinking alcohol. It may increase your risk of liver damage.
This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient’s body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.
Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds), especially if you are being treated for psoriasis. Methotrexate can make your skin more sensitive to sunlight and your psoriasis may worsen.
Methotrexate side effects
Get emergency medical help if you have signs of an allergic reaction to methotrexate (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).
Call your doctor at once if you have:
fever, chills, swollen lymph glands, night sweats, weight loss;
vomiting, white patches or sores inside your mouth or on your lips;
diarrhea, blood in your urine or stools;
dry cough, cough with mucus, stabbing chest pain, wheezing, feeling short of breath;
kidney problems – little or no urination, swelling in your feet or ankles;
liver problems – stomach pain (upper right side), dark urine, jaundice (yellowing of the skin or eyes);
nerve problems – confusion, weakness, drowsiness, coordination problems, feeling irritable, headache, neck stiffness, vision problems, loss of movement in any part of your body; or
signs of tumor cell breakdown – confusion, tiredness, numbness or tingling, muscle cramps, muscle weakness, vomiting, diarrhea, fast or slow heart rate, seizure.
Side effects may be more likely in older adults.
Common methotrexate side effects may include:
fever, chills, tiredness, not feeling well;
nausea, upset stomach;
abnormal liver function tests.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What other drugs will affect methotrexate?
Methotrexate can harm your liver, especially if you also use certain other medicines for infections, tuberculosis, depression, birth control, hormone replacement, high cholesterol, heart problems, high blood pressure, seizures, or pain or arthritis medicines (including acetaminophen, Tylenol, Advil, Motrin, and Aleve).
Many drugs can interact with methotrexate. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor and pharmacist about all your current medicines and any medicine you start or stop using.
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use methotrexate only for the indication prescribed.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Copyright 1996-2020 Cerner Multum, Inc. Version: 14.01.
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More about methotrexate
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Other brands: Rasuvo, Trexall, Otrexup, Xatmep, Rheumatrex Dose Pack
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- a sore throat, raised temperature or fever
- flushing or sweating
- loss of appetite
- bruising or bleeding when you don’t know what has caused it
- yellowing of the skin or eyes, known as jaundice
- any new symptoms or anything else that concerns you.
You should stop taking methotrexate and see your doctor straight away if any of these symptoms are very bad or if you’re becoming really unwell.
In rare cases, methotrexate can cause breathlessness. If this happens to you, see your doctor as in rare cases methotrexate can cause inflammation of the lungs.
You should also see your doctor urgently if you develop chickenpox or shingles, or come into contact with someone who has chickenpox or shingles. These infections can sometimes be very serious in people who are taking methotrexate.
You might need treatment against chickenpox or shingles, and you might be told to stop taking methotrexate until you’re better.
You’re likely to be given folic acid tablets to take on a different day of the week to reduce the side effects of methotrexate. Your doctor will tell you when to take folic acid. Generally, you should avoid taking it on the same day as methotrexate, because it can affect how well it works.
Tips to reduce your risk of infection
- Try to avoid close contact with people you know have an infection.
- Wash your hands regularly and carry around a small bottle of antibacterial hand gel.
- Keep your mouth clean by brushing your teeth regularly.
- Stop smoking if you’re a smoker.
- Make sure your food is stored and prepared properly.
- Try to keep your house clean and hygienic, especially the kitchen, bathrooms and toilets.
USES: Methotrexate is used to treat certain types of cancer or to control severe psoriasis or rheumatoid arthritis. It may also be used to control juvenile rheumatoid arthritis. Methotrexate belongs to a class of drugs known as antimetabolites. It works by slowing or stopping the growth of cancer cells and suppressing the immune system.Early treatment of rheumatoid arthritis with more aggressive therapy such as methotrexate helps to reduce further joint damage and to preserve joint function.OTHER This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.This medication may also be used for lupus, psoriatic arthritis, and ectopic pregnancy.
HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using methotrexate and each time you get a refill. If you have any questions, ask your doctor or pharmacist.This medication is given by injection as directed by your doctor. The dosage, method of injection, and how often you receive this medication are based on your medical condition and response to treatment. For the treatment of rheumatoid arthritis or psoriasis, this medication is given by injection as directed by your doctor, usually once a week.For some conditions (such as rheumatoid arthritis), you may be taught to give yourself injections at home. In this case, learn all preparation and usage instructions from your health care professional. If you have any questions, ask your health care professional.Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid.Learn how to store and discard medical supplies safely.
SIDE EFFECTS: See also Warning section.Nausea, vomiting, stomach pain, drowsiness, or dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Temporary hair loss may occur. Normal hair growth should return after treatment has ended.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: mouth sores, diarrhea, signs of anemia (such as unusual tiredness, pale skin), signs of liver problems (such as dark urine, persistent nausea/vomiting, stomach/abdominal pain, yellowing eyes/skin), easy bruising/bleeding, black stools, enlarged glands/lymph nodes, bone pain, unusual pain and discoloration of the skin, change in the amount of urine, dry cough, muscle weakness.Get medical help right away if you have any very serious side effects, including: irregular heartbeat, vision changes, weakness on one side of the body, severe headache, neck stiffness, mental/mood changes, seizures.This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infection (such as fever, chills, persistent sore throat, cough).This medication can affect sperm production, an effect that may lower male fertility. Consult your doctor for more details.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Rheumatoid Arthritis (RA) Symptoms & Treatment See Slideshow
11 Common Questions About Taking Methotrexate for Rheumatoid Arthritis
Check any message board in a rheumatoid arthritis (RA) group on social media and there’s one topic that pops up in posts constantly. It usually reads like this: “My doctor prescribed me methotrexate (MTX) and I’m terrified. Should I take it?” Then a stream of about 200 comments follows, about mouth sores and hair falling out and diarrhea, and it scares the beejesus out of you even more.
Taking any new medicine can be intimidating, especially one you might have to take for the rest of your life. Often, our doctors prescribe pills, injections, or infusions we’ve never heard of, and we’re either too shy or shocked to ask important questions about what the heck they are and what they might do to our bodies.
For anyone with RA, initiation into the MTX club seems particularly harrowing. I admit that I waited weeks to start taking it when I first got diagnosed with RA. But the truth is, it really wasn’t necessary to freak myself out. I wish I had known that but I, too, did not ask for or look for good information to ease my anxiety.
I admit that I waited weeks to start taking it when I first got diagnosed with RA. But the truth is, it really wasn’t necessary to freak myself out.
I interviewed my RA doctor, rheumatologist Gary Feldman, MD, medical director of Pacific Arthritis Care Center in Los Angeles, about methotrexate. “We’ve been using it since the late 1960s and we have a phenomenal amount of clinical data on tens of millions of patients,” he tells CreakyJoints. Here, he answers 11 of our most common questions and addresses our biggest concerns about methotrexate.
1. How does methotrexate work? Is it a pain pill?
“Methotrexate works on inflammation, it doesn’t work on pain,” Dr. Feldman explains. “But your inflammation causes pain. It’s not like someone poking you with a stick or having a headache. Methotrexate goes to the source of the problem, the inflammation. By reducing that inflammatory process, you help reduce the pain in a more directed way at the source and also in a more effective and long-lasting way. Methotrexate slows down the progression so it reduces the destruction of the joints.”
2. Is methotrexate a cancer drug? Why am I taking a pill for cancer?
The distinction between using methotrexate to treat cancer and to treat rheumatoid arthritis is important. Technically speaking, methotrexate is a “cancer drug” — and it’s used to treat different kinds of cancer, including breast cancer. That’s because methotrexate attacks fast-dividing cells, which include cancer cells.
“But cancer patients take much higher doses of methotrexate for shorter amounts of time than RA patients,” says Dr. Feldman. “The doses for cancer therapy are actually almost 50 times higher. For RA patients, methotrexate is used in a completely different way.”
At these extremely lower doses, methotrexate has a completely different effect on the body. It is a disease-modifying agent that reduces inflammation. “I like to say it’s the difference between swimming in a pool and drinking a glass of water. Both use water but have a different effect,” says Dr. Feldman.
3. What’s the difference between taking methotrexate pills and getting shots?
Methotrexate is available in pill form or as a shot you inject. (Your rheumatologist will likely try the pills first because most people don’t want shots.) Oral methotrexate is available in 2.5 mg tablets. For adults with RA, the starting dose of methotrexate is usually around 7.5 to 15 mg a week (three to six tablets), depending on your disease activity or presence of co-occurring diseases, with the dose increasing as needed to control RA symptoms. The maximum dose is usually 25 mg/week.
“However, once you go over 15 mg per week, the methotrexate can become more difficult to absorb,” says Dr. Feldman. If taking more than 15 mg of MTX orally once a week isn’t working well for you, your doctor might recommend you try methotrexate injections or with splitting the oral dose into two doses over a 12-hour period. The potential side effects would be the same regardless of which form of methotrexate you take.
4. How long will methotrexate take to start working?
It’s not immediate. Many RA patients will start to experience an improvement in symptoms after six to eight weeks on methotrexate, but it can take up to six months before you would reach the full benefits of taking the drug. If you’re having a lot of debilitating RA symptoms, your doctor may prescribe corticosteroids as a short-term treatment to tamp down your RA flares while the methotrexate starts kicking in.
5. Why do I have to take folic acid? Should I take it on the same day as MTX or not?
Folic acid is a type of B vitamin. It’s currently recommended that all patients on low-dose methotrexate take folic acid (1 mg a day) to help offset potential side effects that come with taking methotrexate. The most concerning side effect would be any suppression of bone marrow cells, which produce new blood cells.
Some doctors advise that patients skip folic acid the same day or days you take methotrexate, believing it lessens the effects of methotrexate. Other doctors, including Dr. Feldman, think it doesn’t matter. “I personally don’t have a problem with my patients taking folic acid every day,” he says. “I haven’t seen any good studies to show that it negates the effects of methotrexate. Though I find that some patients find it hard to remember to exclude it on certain days.”
6. What are the worst side effects of methotrexate? Is my hair going to fall out?
Message boards are flooded with questions and comments about all sorts of gnarly side effects. Dr. Feldman admits that everyone reacts differently to methotrexate, but he insists that most side effects are mild and controllable.
“The most common side effects are fatigue a day or two after you take methotrexate, which is why I suggest taking it at night,” he says. “Also gastrointestinal issues. Your stool may be loose, or you may feel queasy or nauseated for a day or two after. Hair thinning and loss does happen, but I don’t see it that often and folic acid does tend to minimize that. Mouth ulcers can occur later and methotrexate does make you sensitive to sunlight, so be careful sunbathing. But the most common side effects are fatigue and GI issues.”
7. Can I get pregnant or breastfeed while taking methotrexate?
Absolutely not. “Methotrexate is toxic to a fetus and can cause congenital mutations,” warns Dr. Feldman. Women should wait 90 days after stopping methotrexate to get pregnant. Men, too, should wait 90 days before trying to conceive because methotrexate may affect sperm (the sperm production cycle is 90 days). Do not breastfeed until the drug is completely out of your system. For more information about managing pregnancy with rheumatoid arthritis, check out our family planning patient guidelines.
8. Can I drink alcohol while taking methotrexate?
Methotrexate can affect liver function, which is why doctors will monitor your liver health closely while you take it. Methotrexate isn’t recommended for people who already have chronic liver disease or who are heavy drinkers and have alcohol-related liver damage. Because there is potential for liver damage in people taking MTX, they shouldn’t consume alcohol excessively.
For occasional drinkers, Dr. Feldman says the rules about how much alcohol is safe to drink while taking methotrexate depends on the rheumatologist. “Some doctors insist on no alcohol at all,” he explains. He tends to be a little looser with his patients. “I tell my patients you can have a few drinks per week, just not all at once.”
And don’t have the alcohol two days before you get your blood drawn at the office, he adds, because the alcohol can mess up the liver function test and confuse your doctor. But he thinks a drink here and there is not dangerous for patients without any liver issues.
9. Will methotrexate mess up my immune system?
Methotrexate tinkers with the immune system, but it doesn’t suppress it in the same way that some other RA drugs do. So taking methotrexate is rarely associated with increased infection risk unless you’re also taking other medications at the same time, such as glucocorticoids, immunosuppressive disease-modifying antirheumatic drugs (DMARDs), or biologics. There may be slight increase in infection, Dr. Feldman notes, “but we’re talking about a half a cold per year per person.”
Doctors may recommend patients with severe infections (say, being hospitalized for pneumonia) take a break from methotrexate while they recover, but you can still take it while you have minor infections like an upper respiratory virus or urinary tract infection. However, you should let your rheumatologist know if you have an infection that doesn’t get better after a few days, to make sure it doesn’t develop into something more serious.
10. What about getting vaccines while on methotrexate?
Methotrexate may slightly depress your body’s response to vaccinations, which means they might not be as effective as they would if you weren’t taking MTX. It’s generally advised that you be up to date on your vaccines before starting methotrexate, so ask your doctor about this.
Some doctors might suggest that you take a two-week “methotrexate holiday” following your annual flu vaccine because research shows this can improve your body’s response the vaccine. You can read more about getting the flu vaccine when you have arthritis here.
11. Will I ever need to take biologics?
Doctors may start you on methotrexate alone, which is known as methotrexate monotherapy, or combine methotrexate with other non-biologic DMARDs or with biologic DMARDs.
“For patients who have a more aggressive disease or what we call moderate to severe activity, methotrexate alone might not be adequate,” Dr. Feldman says.
If you aren’t responding to methotrexate after a two-month period, your rheumatologist may try some kind of combination therapy, such as adding sulfasalazine and hydroxychloroquine (called triple therapy) or adding a biologic drug such as etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade).
It would be unlikely that you would skip methotrexate altogether and go straight to a biologic. Also, many insurance companies will not even allow you to start a biologic until you’ve “failed” with methotrexate. Many patients, “if you catch their RA early,” do well on just methotrexate, Dr. Feldman says.
Here’s a final word about methotrexate from Dr. Feldman: “We have a lot of experience using this medication for the last 35 years. There are nuisance side effects for 10 to 15 percent of patients. But we are monitoring you very closely, and if we look at the control studies, it appears to be very effective for a significant portion of RA patients. It may be all you need. In my personal experience, it’s very safe. And it’s the right place to start for most patients. The sooner you get on it, the sooner you’ll know if it works.”
- Can Methotrexate Reduce Heart Disease Risk? What a Fascinating New Study Found
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- 15 Myths About Rheumatoid Arthritis that Can Be Downright Dangerous to Believe
Methotrexate for RA: A ‘fascinating drug’
SNOWMASS, COLO. – “When I started working with methotrexate in 1982, I never would have predicted that methotrexate would become the standard of care in treating rheumatoid arthritis. There’s just no way,” Michael E. Weinblatt, MD, recalled at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
“Even now, 35 years later, we continue to learn more about this fascinating drug,” added Dr. Weinblatt, professor of medicine at Harvard Medical School, Boston.
He highlighted recent developments in this ongoing story and presented some tricks of the trade gained in 35 years of up-close experience with the drug.
Dr. Michael E. Weinblatt
“After 30-plus years we’re still learning more about its mechanism of action. Every time there’s a new paper on a different mechanism, I think we all continue to marvel at this drug. I think the reason it works as well as it does is because it’s a dirty molecule. It works across the board on multiple cell lines and multiple pathways,” according to the rheumatologist.
Enhancing effectiveness of biologics
One of the hottest topics in methotrexate research is the drug’s ability to enhance the effectiveness of many, but not all, biologic agents. All of the anti–tumor necrosis factor (anti-TNF) biologics as well as rituximab (Rituxan) are demonstrably more effective when used in combination with methotrexate. Dr. Weinblatt considers the widespread underutilization of this combination strategy scandalous.
“This is an incredibly important point: All of you use biologics and all of you use methotrexate, but I’ve been depressed by the fact that up to 30%-40% of patients – no matter which data set you look at – are on monotherapy biological therapy,” he said.
He cited data from the ongoing BRASS Registry (Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Registry) to underscore his point that good things happen when biologics and methotrexate are used together. Of 1,395 BRASS Registry participants prospectively followed since 2003, the proportion on biologic therapy has climbed steadily from 41% at the outset to 68% in 2016. Remarkably, 82% of patients on biologic therapy remain on their first biologic agent. Fewer than 4% have switched biologics more than twice. That’s very unlike the experiences reported elsewhere.
“I think one of the reasons we have such positive data is that we have a high percentage of patients staying on their background methotrexate,” said Dr. Weinblatt, codirector of clinical rheumatology and associate director of the Center for Arthritis and Joint Diseases at Brigham and Women’s Hospital, Boston.
He noted that Dutch investigators reported at the 2016 annual meeting of the American College of Rheumatology that among 1,230 consecutive rheumatoid arthritis patients started on etanercept (Enbrel) or adalimumab (Humira), 28% in the etanercept group were on concomitant methotrexate, as were 64% of those who started on adalimumab. The patients spent a median of 1.3-1.6 years and a maximum of 9.2-9.3 years on their biologic agent. Patients on adalimumab monotherapy were 2.61-fold more likely to drop out than were those on dual therapy with methotrexate. Patients on etanercept monotherapy were 1.2-fold more likely to drop out, a difference that didn’t achieve statistical significance.
Although the investigators did not study the mechanism of prolonged on-treatment survival, they speculated that it probably involved methotrexate’s documented ability to prevent formation of anti-adalimumab antibodies. In contrast, patients on etanercept don’t develop blocking antibodies, Dr. Weinblatt observed.
The randomized, double-blind CONCERTO trial conducted in 395 methotrexate- and biologic-naive RA patients demonstrated that methotrexate reduces the immunogenicity of adalimumab in dose-dependent fashion. Participants were randomized to open-label adalimumab at 40 mg every 2 weeks plus weekly double-blind methotrexate at 2.5, 5, 10, or 20 mg. Clinical outcomes at 26 weeks as reflected in 28-joint count disease activity score and the Clinical Disease Activity Index were significantly better in patients on 10 or 20 mg/week of methotrexate than in those on 2.5 or 5 mg/week. Serum adalimumab levels were higher in patients on the two higher doses of methotrexate as well (Ann Rheum Dis. 2015 Jun;74:1037-44).
“It ends up that if you don’t use methotrexate or you use a very low dose you increase the risk of developing antibodies against adalimumab and decrease the efficacy of the drug. So in clinical practice, if you’re going to be working with dose titration of methotrexate and your patient is on adalimumab, there’s a threshold below which you probably shouldn’t go. In this study, doses of 10 mg/week or more induced a greater clinical response,” he said.
With infliximab (Remicade), based upon 20-year-old studies, the threshold is 7.5 mg of methotrexate per week.
“With etanercept, we don’t know what the threshold is. You don’t develop blocking anti-drug antibodies with etanercept, but we do know that methotrexate enhances the efficacy of etanercept, and it doesn’t do it by changing the biologic’s pharmacokinetics and there’s no increase in methotrexate blood levels,” the rheumatologist continued.
Unlike the anti-TNF biologics and rituximab, the efficacy of the Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib is not enhanced when the drugs are used in combination with methotrexate, studies indicate.
The efficacy of certolizumab pegol (Cimzia) wasn’t affected by methotrexate dose category in a prespecified pooled subgroup analysis of the phase III RAPID 1 and RAPID 2 clinical trials. In the 1,273 certolizumab-treated patients, the week-24 treatment response was similar regardless of whether patients were on methotrexate at 10 mg/week or less, 10-15 mg/week, or more than 15 mg/week. The investigators concluded that to minimize treatment-emergent adverse events, physicians can tailor background methotrexate dosing based upon individual patient tolerance without affecting certolizumab’s efficacy (Arthritis Care Res . 2016 Mar;68:299-307).
An important aspect of this analysis was that among the 325 subjects randomized to placebo rather than certolizumab, the treatment response at week 24 was significantly better in those on more than 15 mg/week of methotrexate than with lower doses of the drug.
“Most patients on methotrexate need more than 15 mg/week. So it astonishes me that such a high percentage of patients enrolled in clinical trials around the world are on, like, 14 mg/week. I mean, most patients need somewhere between 15 and 25 mg/week for a response, although over time you might be able to decrease that dose,” Dr. Weinblatt said.
Side effects of methotrexate
“The biggest issue with methotrexate is the tolerability problem, since serious adverse events are incredibly rare with this molecule,” he said.
Hepatotoxicity is a concern, but Dr. Weinblatt emphasized that elevated liver function tests do not equal cirrhosis.
“Historically, during the first 6 months on methotrexate 20%-25% of patients increase their transaminases in every clinical trial where that’s been looked at. Over time, the liver compensates for the drug. But 5%-6% of patients experience repeated moderate elevations more than 1.5 times the upper limit of normal,” he said.
Key risk factors for methotrexate-related hepatotoxicity were identified in a national observational cohort study of 659 military veterans over age 65 when they started methotrexate for rheumatic diseases. The investigators found a 6% incidence of moderately elevated liver enzymes during a mean follow-up period of 7 months. Obesity was associated with a 1.9-fold increased risk, a serum total cholesterol greater than 240 mg/dL conferred a 5.8-fold elevated risk, and abnormal liver function tests at baseline were associated with a 3.2-fold increased risk (Arthritis Care Res . 2014 Aug;66:1159-66).
“No surprise: It’s patients who weigh more who are at increased risk for methotrexate-related transaminase increases. I actually think the biggest factor with regard to methotrexate liver disease is the patient’s . Patients in North America aren’t getting any slimmer, so you need to look at this with your patients. If you have a morbidly obese patient on methotrexate whose transaminases suddenly start going up, that’s the patient who’s at greatest risk for methotrexate hepatotoxicity,” he cautioned.
The 3.2-fold increased risk of repeated elevated transaminases associated with abnormal baseline liver function tests in the Veterans Affairs study should be a red flag for rheumatologists.
“I personally think patients shouldn’t start on methotrexate if they have elevated transaminases. They ought to be normal at the start. There are too many other good options now to treat our patients,” Dr. Weinblatt said.
He reported receiving research grants from half a dozen companies and serving as a consultant to more than two dozen.