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Updated on February 12, 2012


This article is about the prescription medication known as Methotrexate. Most people will never take this medication, and many will not have ever heard of it. But for those suffering from various forms of arthritis or cancer, methotrexate may be quite familiar, a weekly partner in their road to recovery or symptom control. This article is for those who are taking, or are considering taking methotrexate. You are wondering: "What is methotrexate?" I will try to answer that question.

Many people wrongly assume that all pharmacists are blindly enthusiastic about every medication on our shelves. The fact is that there are risks and benefits that must be weighed every time we pop a pill. Some drugs have the potential for serious side effects. Patients should have the opportunity to learn about these risks, and also the potential benefit, and make an informed and educated decision. Often our health care system does not offer the opportunity to get all the questions you may have answered. This article on Methotrextate, and other similar articles, is my attempt to give you some facts on which to make your decision.

In this article I will try to provide some honest information about both the benefits and risks/side-effects associated with this drug. I will do my best to give a balanced perspective. I hope you will find the information about methotrexate helpful. I am also mindful, as I write, that many readers will know far more personally than myself the painful reality of these conditions treated by methotrexate. I consider it a privilege to serve you and admire your strength and courage in managing these often-misunderstood illnesses.

Methotrexate tablets on a pharmacy counting tray
Methotrexate tablets on a pharmacy counting tray

What Exactly Is Methotrexate?


Pronounce methotrexate with 4 syllables: Meth-o-trex-ate.

Methotrexate, which is sometimes abbreviated as "MTX" has been in use since about the 1950s. It is used in the treatment of certain types of cancer and also rheumatoid conditions.

Methotrexate is available only by prescription in 2 dosage forms:

  • Injectable: 25mg/ml, 50mg/2ml and 1,000mg/40ml
  • Tablets: 2.5 (brand name Rheumatrex) and 5mg, 7.5mg, 10mg. 15mg (brand name Trexall). The 2.5mg tablets are available generically.

The way Methotrexate works to treat cancers is understood better than the way it works to treat arthritis conditions. In cancer, methotrexate works by interfering with the synthesis of DNA and RNA. Specifically, it attracts the attention of an enzyme "dihydrofolate reductase" (DHFR). While DHFR is busy playing with methotrexate, it conveniently is unavailable to metabolize folic acid into an important building block of DNA and RNA.

Without the proper manufacturing of DNA and RNA...cells cannot replicate. The cells influenced most critically are those which undergo rapid replication...i.e....cancer cells!

Types of cancers treated with methotrexate (and often other oncology drugs in combination) include:

  • Breast Cancer
  • Epidermoid Cancers
  • Lung Cancer
  • Non-Hodgkin's Lymphomas

Methotrexate is also used to treat certain types of rheumatoid conditions. These include:

  • Rheumatoid Arthritis
  • Juvenile Rheumatoid Arthritis
  • Plaque Psoriasis

How exactly methotrexate works in treating these rheumatoid conditions is not entirely clear, although it may be related to its effect on the immune system. Methotrexate is not a cure for these rheumatoid conditions. It helps to reduce the symptoms and severity, while allowing patients to potentially maintain a normal active lifestyle while reducing the discomfort associated with this disease.

Methotrexate Side Effects

Methotrexate is a potent medication. As with all strong medications, while they offer many potential advantages, they also carry serious risks that need to be considered.

Some of the more common and less serious side-effects associated with methotrexate include:

  • Stomach pain
  • Nausea
  • Hair loss (this will return after completing methotrexate)
  • Vomiting
  • Dizziness, Drowsiness or Fatigue.

If these side effects become persistent and too hard to manage, contact your prescriber. As I talk to patients and contribute to discussions about this drug on various medication forums, I would say that the fatigue and nausea tend to be the things I hear complained about most of all. Many patients, however, who are able to make it through the first few weeks or months, find they enjoy significant improvement in their symptoms and that these side-effects lessen in severity over time.

More serious side-effects that should be reported immediately include:

  • Moth sores
  • Unusual Bleeding or Bruising
  • Chest pain
  • Difficulty breathing
  • Yellowing of the skin or eyes (a sign of liver problems)

Okay, so now you know the good, the bad and the ugly side of Methotrexate.


Folic Acid: Methotrexate may cause folic acid deficiency, which may lead to anemia and other side effects. To prevent this, your doctor may recommend taking a daily dose of folic acid, from 1mg to 5mg daily. You can find this in the vitamin section of your local pharmacy, or your doctor may also prescribe it for you.

Pregnancy: Methotrexate may cause birth defects and therefore females taking methotrexate must ensure that they do not become pregnant while taking this medication. Female patients of child-bearing potential will be required to take a pregnancy test before beginning treatment and must ensure pregnancy is prevented during treatment (and up to 2 months after discontinuation). Methotrexate may also interfere with fertility in females and reduced sperm count in males.

Sunlight & Sunscreen: Methotrexate may make your skin more sensitive to the sun. Avoid prolonged sun exposure and where an appropriate sunscreen if sun exposure is unavoidable.

Blood Work: Patients taking methotrexate will be required to have some beginning blood-work done, as well as regular follow-up blood work. Specifically they will be looking for signs of toxicity which might impact kidney function, liver function, blood cell formulation (anemia) and immune system activity. Thankfully, with careful monitoring, any concerns can be rapidly addressed and any prolonged and serious risks can be avoided. Pulmonary (lung function) tests may also be suggested.

Cancer: No well controlled human studies are available on the cancer-risks associated with methotrexate. Animal studies are not conclusive. Some reports of cancers have arisen during methotrexate therapy, but a cause-effect relationship cannot be certain.

Weekly Dosing: MOST often methotrexate is taken ONCE A WEEK. Sometimes the dose will start out low (1-3 tablets per week) and may increase depending upon your response to treatment. Another dosing schedule is to take 3 doses separated by 12 hours once a week. Be VERY careful to take this medication ONLY as prescribed and be sure to document on a calendar or other document exactly when and how many tablets you took. It does not matter which day of the week you take methotrexate, although some patients plan the dose so that they have a day to recover from any side effects.


Drugs that could potentially increase the blood levels of methotrexate might raise the risk of toxicity. These include NSAIDs (like ibuprofen, naproxen, indomethacin, etc) and aspirin. Certain patients who have previously and regularly been taking NSAIDs may be able to continue them while starting methotrexate. Seek advice, however, before initiating therapy with these. Additional monitoring may be advised.

Penicillin antibiotics can also increase the risk of methotrexate toxicity. Be sure to let any doctor you see know that you are taking methotrexate before they prescribe for you. If possible, always use the same pharmacy for your medications also. That way they can check your profile for drug interactions every time you get a prescription filled.

A Final Question...

WHEN WILL IT START WORKING? Maybe you have read this article because your doctor has suggested methotrexate. My goal has not been to persuade you in one way or the other. I personally believe there are many situations where this drug has been safely and effectively used. For many it has allowed significant improvement in the activities of daily living. But how soon can you expect to see results? Typically, when used for rheumatoid conditions, the effects of methotrexate are not noticed for several weeks, sometimes not before 1-2 months. You will need some patience and persistence. Not everyone will enjoy total success with this medication. But many patients find that it has improved their quality of life immensely.

For those who ARE helped, continuation of therapy will be necessary. Once discontinued, rheumatoid symptoms tend to return within several weeks.

For More Information:

A great patient leaflet on the use of Methotrexate is available HERE.

An article on Rheumatoid Arthritis from John Hopkins Medicine can be found HERE

Do you have any insights into Methotrexate or experiences with Methotrexate you want to share? Feel free to comment below. Your further questions are also welcomed.


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    • Pamela99 profile image

      Pamela Oglesby 

      19 months ago from Sunny Florida

      I was on the med for about 2 years to treat Systemic lupus, along with prednisone. As a RN I chose to inject the med as I had less stomach issues that way. My doctor prescribed another medicaiton to help with the side effects that I could take a certain number of hours after the injecton or maybe the next day as I can't remember right now.

      That was before Benesta was developed, and there was no treatment for lupus at the time. Now, many years later I am sufferng from the side effects from being on prednisone too many years, but I don't think I have long term side effect fro methotrexate. I will say I felt awful when I was taking it, but that may have been due to the lupus flare-ups.

      Great article that spelled out the pros and cons of this med.

    • bersihaman profile image


      5 years ago from Purbalingga jawa tengah

      nice article

    • profile image


      8 years ago

      Is it Possible to design a formulation containing both Methotrexate and Folic Acid or its Active form Folinic Acid/Leucovorin in the same?

    • pharmacist profile imageAUTHOR

      Jason Poquette 

      8 years ago from Whitinsville, MA


      I signed, and encourage others to do the same. I also called Mylan, one of the 3 manufacturers of MTX pf formula. They are currently in-stock and allocating from their warehouse in TN. Providers can place orders and ask for a drop-ship. They are also increasing production. The supply issue is with a different manufacturer right now.

    • profile image


      8 years ago

      Go to this blog & help sign the petition to help Grayson & other children who need this drug to fight cancer! Every bit helps!

    • pharmacist profile imageAUTHOR

      Jason Poquette 

      8 years ago from Whitinsville, MA


      Thanks for the kind words!

    • teaches12345 profile image

      Dianna Mendez 

      8 years ago

      Thank you for posting information on methotrexate. I do not have to take this for any reason mentioned above but I do like to keep informed about medicines and their benefits/side effects. Your writing style makes it easy for non-medical professionals, like myself, to absorb and understand.

    • healthwriterbob profile image


      8 years ago from United States

      Good summary of the most important facts about methotrexate. For some people, the side effects can be troublesome. Take care. Voted up and useful.

    • pharmacist profile imageAUTHOR

      Jason Poquette 

      8 years ago from Whitinsville, MA


      That is pretty interestinig. I did not know about this use of mtx. Yes, I have heard about the potential shortages of mtx. The news reports I saw were vague, and seemed to suggest the manufacturers had slowed production due to profit issues...but I can't recall exactly. Hopefully they can rev up the process as so many people, especially children, depend upon mtx for treatments.

    • pharmacist profile imageAUTHOR

      Jason Poquette 

      8 years ago from Whitinsville, MA

      Writer20, appreciate your kind words and support! Thanks!

    • Kris Heeter profile image

      Kris Heeter 

      8 years ago from Indiana

      I thankfully have never had to take it, but ironically we use this a common drug in my primarily area of biological research (we grow insect cell lines that can grow only in the presence of MTX).

      I did just recently see a headline that implicated a big manuafacturer of MTX may halt production and that it had some cancer patients worried - just curious on your thoughts or insight on that?

    • Frank Atanacio profile image

      Frank Atanacio 

      8 years ago from Shelton

      thank you for this insightful, educational share...up and useful..Frank

    • writer20 profile image

      Joyce Haragsim 

      8 years ago from Southern Nevada

      Great information for us with this darn problem. Thank you for alerting us. voted up,intesting and useful,Joyce


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