| What is it? Methotrexate (Rheumatrex) is a medicine that is used to treat rheumatoid arthritis (RA) psoriatic arthritis Reiter's syndrome and other conditions. |
History of methotrexateFirst developed to treat certain types of cancer methotrexate is routinely used at higher doses as a cancer therapy and is now used at much lower doses to treat rheumatic diseases like rheumatoid arthritis. Methotrexate has been studied for over 20 years in the treatment of rheumatoid arthritis and in 1988 was approved for this use in adults by the U.S. Food and Drug Administration (FDA).
How it works
This medicine acts by altering the body's use of folic acid (a vitamin) which is needed for cell growth. Scientists suspect that this interference with folic acid is an important reason for methotrexate's benefit in rheumatoid arthritis. Methotrexate belongs to a group of medicines that are called "second-line therapies" or "disease-modifying anti rheumatic drugs." These drugs may affect the activity of RA to a greater extent than commonly prescribed drugs such as aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Methotrexate is usually taken along with NSAIDs. It may begin to work as early as three to six weeks after beginning treatment.
Methotrexate is used in both children and adults with active or progressive rheumatoid arthritis although FDA approval is only for adults. It may be prescribed after trying one or more other second-line therapies such as antimalarials or gold salts. It also may be recommended even before starting these drugs. The decision to begin methotrexate will be based upon the opinions of both you and your doctor regarding the progression and activity of your disease. Methotrexate benefits a high percentage of those who use the drug. This improvement includes a decrease in the number of painful and swollen joints as well as an overall reduction in RA disease activity. Patients with rheumatoid arthritis who do not respond to methotrexate often are good candidates for surgical reconstruction of their damaged joints such as total hip arthroplasty total knee arthroplasty and total shoulder arthroplasty.
| Common dosage |
Methotrexate is taken once a week either orally (as pills) or by injection. The tablet strength is 2.5 milligrams and the starting dose is usually three pills (7.5 milligrams) taken one day a week. The dose may be increased over time if there is no initial benefit. Generally doses between 7.5 and 20 milligrams one day a week are used to treat rheumatoid arthritis. Doses higher than 20 milligrams weekly may occasionally be used.
If taken orally methotrexate may be taken all in one dose or split up and taken two or three times over a 24-hour period once a week. For example you can take it all on Monday morning or on Monday morning Monday evening and finally on Tuesday morning. It may also be given injection either just under the skin in the muscle or directly into the vein. Injections may be recommended for people who are not responding to oral methotrexate or are developing intestinal side effects such as nausea.
ToxicityMethotrexate should not be taken more often than one 24-hour period per week and should be taken on the same day each week. More frequent administration can be associated with serious side effects. Mark a calendar to remind yourself when to take your dose. If you become confused about when to take the drug call your doctor to clarify the situation before you take the next dose.
Whenever a new medication is recommended consult your doctor to make sure there is no problem taking it with methotrexate. You should not take the antibiotic trimethoprim/sulfamethoxazole (Bactrim or Septra) with methotrexate. In some people a shortage of folic acid can occur with methotrexate therapy. Therefore your doctor may prescribe supplemental folic acid pills.
Frequently children with juvenile rheumatoid arthritis and related forms of pediatric arthritis are also commonly treated with methotrexate usually by mouth but occasionally by intramuscular or intravenous injection. The side effects are similar in children and adults. Dosages of methotrexate for children are calculated by body weight or body surface area and are then adjusted as the child grows. Methotrexate treatment for children with arthritis may help them more easily attend school achieve normal stature and reach other age-appropriate developmental milestones.
Even though methotrexate has not yet received approval from the U.S. Food and Drug Administration for use in JRA it is being used widely by arthritis specialists to treat this disease.
Pregnant or nursing mothers
Methotrexate may cause birth defects if taken by a woman at the time of conception or during pregnancy. Women of childbearing potential must use birth control and must not get pregnant while receiving methotrexate. After methotrexate treatment is stopped women should wait at least one menstrual cycle before trying to conceive. Methotrexate has no effect on fertility and if the drug is stopped at least 30 days prior to attempting conception there will be no effect on the unborn child.
Breast-feeding is not recommended while taking methotrexate because the medicine may be passed to the child through the mother's milk.
| Common side effects |
Side effects do occur in some people taking methotrexate. At the low weekly doses used to treat rheumatoid arthritis however serious side effects are rare.
The most common side effects include upset stomach nausea vomiting loss of appetite diarrhea or mouth sores. If these develop you should contact your doctor immediately. A change in the dose or in how you take your methotrexate may reduce these side effects.
Occasional side effectsOccasionally side effects such as headaches dizziness mood alterations skin rashes or unexplained weight loss may occur. Increased sensitivity to sun has also been observed although this is rare. Your blood count may decrease but this uncommon with weekly low doses of methotrexate. This could include a decrease in the number of white blood cell that help fight infection. A decrease in the platelet count or red blood cell count may also occur which could lead to bruising bleeding or fatigue. Factors that increase the possibility for these blood cell changes with methotrexate include pre-existing kidney disease low levels of folic acid certain infections and the use of certain medications including an antibiotic called trimethoprim/sulfamethoxazole (Bactrim or Septra).
Long-term side effects
Rarely lung damage occurs with this drug. Call your doctor immediately if you develop a cough progressive shortness of breath and fever.
Methotrexate may also cause liver damage although this is rare in patients with RA. Since regular use of alcoholic beverages can increase the risk of liver damage you are advised to stop drinking alcohol while on methotrexate. This issue should be discussed with your doctor.
Blood tests will be done on a regular basis to monitor your liver and bone marrow for changes. After several years of methotrexate therapy your doctor may recommend a liver biopsy to examine directly the effects of methotrexate on your liver. At this time there are no standard recommendations on the necessity or timing of doing a liver biopsy. If you have concerns or questions they should be discussed with your doctor.
Methotrexate may lower the sperm count in men. The sperm count should normalize with drug discontinuation. There is little information available regarding the risk of birth defects from a father taking methotrexate at the time of conception. However it is recommended that males discontinue methotrexate three months prior to attempting conception.
Risk factors for side effects
If you should get the flu or another infection you should call your doctor promptly to find out if you should continue to take your methotrexate while you are sick. Dehydration (loss of fluids) can increase your risk of side effects.
To reduce the potential for side effects from methotrexate regular laboratory tests are absolutely necessary. Prior to starting methotrexate standard blood tests should be performed. A chest X-ray is strongly recommended. Once you start therapy routine blood tests will be performed. The time between tests will be shorter at the beginning of therapy and may be longer when you are on maintenance therapy.
Please be certain to keep your scheduled laboratory monitoring and doctor appointments since many side effects can be detected before they become serious. Side effects are often a sign that your medication should be changed or stopped. Sometimes a change in dosage of methotrexate will eliminate or alleviate side effects.
| Talking to your doctor |
The decision to start methotrexate or any second-line drug is a critical part of the treatment of a child or adult with rheumatoid arthritis. It is important for a specialist in arthritis to be a part of this decision. If you are under the care of another type of doctor it is appropriate to ask about a consultation with an arthritis specialist before you begin treatment with methotrexate. Since methotrexate is used for other conditions other doctors completely familiar with the effects of methotrexate may dispense and monitor the drug but periodic re-evaluation with a arthritis specialist is recommended for people with RA and JRA.
Things to remember
Taking your medication incorrectly can result in serious side effects. To gain the greatest benefit from methotrexate follow this advice:
As with other drugs used to treat adult and juvenile RA there is no guarantee that methotrexate will work for everyone. Patients with rheumatoid arthritis who do not respond to methotrexate often are good candidates for surgical reconstruction of their damaged joints such as total hip arthroplasty total knee arthroplasty and total shoulder arthroplasty. However many arthritis specialists agree that when methotrexate is properly used the risk of side effects is less than the risk to your health from the disease itself. Talk to your doctor about your disease and the treatments available to you. Communication between you and your doctor is important.
The Arthritis Foundation and the University of Washington Department of Orthopedics do not endorse any brand name or generic name medication listed here.
Some of this material may also be available in an Arthritis Foundation brochure. Contact the Washington/Alaska Chapter Helpline: (800) 542-0295. If dialing from outside of WA and AK contact the National Helpline: (800) 283-7800.
Adapted from a pamphlet originally prepared for the Arthritis Foundation. This material is protected by copyright.