Methotrexate is a very commonly prescribed RA medication and is the most popular of the disease-modifying antirheumatic drugs (DMARDs). It is also known by its brand name, Rheumatrex (Stada Pharmaceuticals).
Methotrexate is classified as an antimetabolite drug, which means it is capable of blocking the metabolism of cells. It is particularly effective in suppressing rapidly dividing cells, such as those found in the inflamed joints of people with RA. This drug is effective in both reducing the signs and symptoms of RA and slowing disease progression and joint damage. Its effects start within weeks after you first begin to take methotrexate, but can take months to reach their full effectiveness. Methotrexate's ability to improve symptoms depends on how high a dose you take. Ordinarily, doctors prescribe a low dose initially, between 7.5 and 15 milligrams per week. This dose is increased until symptoms improve, which may take several months. People rarely tolerate doses higher than 20 to 25 milligrams.
Methotrexate has many positive attributes:
- It is effective in most patients with RA (70% of patients have some response).
- It begins to work within four to six weeks.
- It has fewer side effects than some other DMARDs.
- It is well tolerated for long periods of time (the majority of patients will still be on the drug after five years).
- It is easy to administer (weekly pills or injections).
- It is relatively inexpensive.
Methotrexate can be taken as pills or can be given as a subcutaneous (under the skin) injection. Some people may experience nausea after taking methotrexate orally. Taking the medication as a subcutaneous injection seems to reduce or eliminate this problem. Giving the methotrexate as an injection in the skin allows for the use of a small needle (the size of an insulin needle), and a relatively painless injection. Intramuscular injections can hurt a bit. However, many people find they can tolerate higher dose of methotrexate when it is given by an intramuscular injection, because it seems to cause less nausea.
Common side effects of methotrexate include nausea, stomach upset, hair loss, and stomatitis. Stomatitis is an inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, and roof or floor of the mouth. People who experience this side effect usually don't have visible ulcers in their mouth, but they may have a lot of pain and difficulty eating.
Rare and more serious side effects of methotrexate are those affecting the liver, lungs, and bone marrow. The liver can become inflamed as a result of methotrexate, a condition known as hepatitis. Prolonged exposure in some people can result in the liver becoming filled with nonfunctioning fibrous tissue, a condition called hepatic cirrhosis. The incidence of real toxicity is probably on the order of 1 in 1000 patients over a five-year treatment period. Your doctor will monitor your blood tests to make sure you aren't developing problems with your blood or your liver if you take methotrexate.
Patients who take methotrexate can also develop fibrosis of the lungs, an uncommon but potentially fatal complication known as interstitial pneumonitis. The risk factors for methotrexate-related lung disease are not well understood, but may include preexisting lung disease or an abnormal chest radiograph.
Methotrexate can also suppress the production of blood cells and platelets in the bone marrow. Because of these risks, before you start taking this medication, your physician should order baseline studies of your blood, liver, and lungs to confirm that you're not at high risk for developing these complications. Some specific studies you should have before beginning methotrexate therapy include the following tests:
Platelet
An irregular, discshaped element in the blood that assists in blood clotting.
- A complete blood count (CBC)
- Liver function chemistries and tests for hepatitis B and C
- Serum creatinine level (a measure of kidney function)
- Chest x-ray and pulmonary function tests
Once you begin taking methotrexate, your doctor should order a CBC and tests of liver and kidney function every four to eight weeks.
Folic acid (a B vitamin), in a dose of 1000 micrograms per day, is usually prescribed for people who take methotrexate in an effort to prevent many of the side effects associated with this medication. Some people will do well on methotrexate without folic acid; of course, given that the folic acid doesn't decrease the efficacy of the methotrexate, it seems like a wise precaution to take it just in case side effects do occur. Occasionally, higher doses of folic acid are used in conjunction with methotrexate, or other forms of folic acid such as folinic acid are used.
Methotrexate can be combined safely with nearly every other FDA-approved DMARD for RA, including NSAIDs, sulfasalazine, hydroxychloroquine, leflunomide, and tumor necrosis factor (TNF) inhibitors. No unexpected toxicities have been observed in medical studies when methotrexate was combined with one of these DMARDs.
Not all patients are good candidates for methotrexate therapy. If you have problems with your liver, kidneys, or bone marrow, you should notify your physician before you begin taking methotrexate. People who have chronic obstructive pulmonary disease (COPD, also known as emphysema), renal insufficiency, or acute or chronic liver disease; people who abuse alcohol; people who are malnourished; and people who have some blood diseases may also be at a higher risk for experiencing methotrexate's side effects.
I've been on methotrexate since 1993. This medication works for me in the pill form. I do have flare ups when they cut back on the number of pills or when the weather (seasons) changes. I have blood work done on a monthly basis.
—Jim