Methotrexate is given weekly either as a shot (injection)
or by mouth (orally).
How It Works
Methotrexate interferes with the
production and maintenance of DNA, the genetic material in the cells of your
body. It is not known exactly how methotrexate works in
rheumatoid arthritis, but it can reduce inflammation
and slow the progression of the disease. Methotrexate is considered a
disease-modifying antirheumatic drug (DMARD). DMARDs are also called
immunosuppressive drugs or slow-acting antirheumatic drugs (SAARDs).
Why It Is Used
Methotrexate reduces inflammation
caused by rheumatoid arthritis. It is the most common DMARD used to treat
rheumatoid arthritis.1 Methotrexate may be
- In the early stages of rheumatoid arthritis to
prevent disease progression.
- In combination with other medicines
such as other DMARDs.
How Well It Works
Methotrexate is effective in
relieving joint inflammation and pain, slowing disease progression, and
preventing disability by delaying joint destruction.2
People with rheumatoid arthritis may be more likely to continue treatment with
methotrexate than with other DMARDs because of favorable results and tolerable
side effects. Studies indicate that more than 50% of people who take
methotrexate for rheumatoid arthritis continue taking the medicine for more
than 3 years, which is longer than any other DMARD.3
Methotrexate is often the first DMARD prescribed
for rheumatoid arthritis and usually provides relatively fast relief of at
least some symptoms. If you can tolerate methotrexate, but it is not effective,
your rheumatologist will recommend that you take another DMARD along with
methotrexate (combination therapy). Several recent studies report that
treatment results are improved when methotrexate is given with another DMARD.
For example, one study found that methotrexate used in combination with
etanercept, a new DMARD, is more effective at reducing disease activity than
methotrexate alone.4 Studies with infliximab and
adalimumab have shown similar results.1
Combination therapy may allow for lower doses of an individual drug to be used,
which may reduce the risk of adverse effects that can occur with higher doses.
In one large review of studies, various combinations of DMARDs plus
methotrexate were more effective than either methotrexate or another DMARD
Common side effects, which are reversible
once the medicine is stopped, include:
- Hair loss.
- Mild liver inflammation (elevation of liver enzyme blood
- Fatigue and feeling like you have the flu.
- Low blood counts.
Folic acid supplements may help prevent some of these
minor side effects. But do not take folic acid without consulting your health
Risk of infection
Methotrexate decreases the
activity of your body's immune system, which increases the risk of a serious
bacterial infection. Some people who take methotrexate develop an infection
that requires oral antibiotics; a smaller number of people will develop an
infection that requires intravenous antibiotics and hospitalization. Contact
your health professional if you develop any of the following symptoms:
- Fever or chills
frequency of or burning during urination
- A cough with yellow
sputum or shortness of breath
- A skin
- Severe abdominal pain or diarrhea
- A severe
- Sinus pain with yellow
- A painful, burning rash in a band
across one side of your body (shingles)
widespread mouth sores
Low blood counts are an uncommon side effect and are
reversible once the medicine is stopped.
Rare side effects
Liver damage (not reversible).
inflammation or damage.
Regular blood tests may help detect liver damage early so
that the dose can be adjusted accordingly. If you develop any of the more
serious side effects listed above, call your health professional
People with rheumatoid arthritis have a slightly
higher risk of getting cancer of the lymph glands, called
lymphoma, than people without the disease. But
lymphoma is rare even for people with rheumatoid arthritis. Experts do not know
why this risk is higher for people with rheumatoid arthritis-it may be because
the disease is severe or because of the medicines used to treat it. Studies are
currently under way to explain this. Talk with your health professional about
the benefits of DMARD therapy and the potential risks of treatment.
Your health professional may want you to have a chest X-ray taken before
starting treatment with methotrexate. If you develop a cough and shortness of
breath while on methotrexate, contact your health professional
See Drug Reference for a full list of side effects.
(Drug Reference is not available in all systems.)
What To Think About
Avoid using alcohol if you are
taking methotrexate for rheumatoid arthritis.
Methotrexate should not be used by pregnant women or women of
childbearing age who are not using reliable birth control. If you are going to
take methotrexate, you should be on some form of reliable birth control. If you
plan to become pregnant, check with your health professional before stopping
birth control and trying to become pregnant.
If you are taking
methotrexate, talk to your health professional before taking any other
- Penicillin antibiotics.
While it is generally safe to take nonsteroidal
anti-inflammatory drugs (NSAIDs), such as aspirin, with methotrexate, it is
best to talk with your health professional if you plan to do so. Methotrexate
is eliminated by the kidney, and NSAIDs could decrease kidney function, so it
is possible that clearance of methotrexate from the body could be affected by
There may be a slight increase in the risk of developing
certain infections, such as
If you have a history of liver
disease, such as viral or alcoholic hepatitis, talk with your rheumatologist
before taking methotrexate.
Complete the new medication information form (PDF)(What is a PDF document?) to help you understand this medication.
Drugs for rheumatoid arthritis (2009). Treatment Guidelines From The Medical Letter, 7(81): 37-46.
Walker-Bone K, Fallow S (2007). Rheumatoid arthritis,
search date June 2005. Online version of BMJ Clinical Evidence. Also available online:
Kwoh CK, et al. (2002). Guidelines for the management
of rheumatoid arthritis. Arthritis and Rheumatism,
Klareskog L, et al. (2004). Therapeutic effect of the
combination of etanercept and methotrexate compared with each treatment alone
in patients with rheumatoid arthritis: Double-blind randomised controlled trial.
Lancet, 363(9410): 675-681.
Donahue KE, et al. (2008). Systematic review:
Comparative effectiveness and harms of disease-modifying medications for
rheumatoid arthritis. Annals of Internal Medicine,