Like the other immunosuppressants, methotrexate can produce side effects. The most commonly reported problems involve stomach intolerance and mouth sores. Nausea, vomiting, and diarrhea can usually be minimized by dividing up the weekly dose; that is, the standard prescription for methotrexate calls for taking the complete weekly dose all at one time, once a week. Anyone who experiences stomach problems from methotrexate can take one pill every several hours on that one day of the week (if your dose is three pills per week, for example, you would take one pill every eight hours on the day of your treatment). You cannot divide the dose up throughout the week, however. Your doctor will help you with a schedule that is tolerable for you. Other possibilities include taking the medication with food, adjusting the dose, and taking anti-nausea medications. Some people tolerate an intramuscular shot of methotrexate better than the pill form.
The most frequent side effect that causes concern involves the liver. In people taking methotrexate, blood tests that measure liver enzymes are frequently elevated slightly, but this is rarely an indication of a serious liver problem. With long-term use, however, inflammation and scarring of the liver can take place. Although cirrhosis of the liver is a distinctly rare side effect, some people with psoriatic arthritis have developed cirrhosis of the liver from methotrexate. Scarring and cirrhosis appear to be much less common in RA patients. The risk of liver problems can be minimized greatly if the person avoids alcohol and keeps his or her weight down. After several years of methotrexate use, a liver biopsy may be indicated, particularly if liver blood test abnormalities persist.
Blood counts (white and red blood cells and platelets) can be lowered by methotrexate use. At the dose used to treat RA, this side effect is unusual. When it occurs, it is almost always reversible by discontinuing the use or reducing the dose of the drug. Reduced platelet counts increase bleeding risks in some people. When the white blood cell count is markedly lowered, serious infections can occur; much more rarely, unusual or atypical infections develop while white blood counts are at normal levels. These infections can develop because of methotrexate’s effect on the immune system.
Another serious side effect is lung inflammation or pneumonitis. This inflammation is generally reversible with discontinuation of methotrexate and treatment with corticosteroids. Pneumonitis can, on rare occasions, be life threatening.
Recent studies that suggest that taking folic acid (or folate) supplements decreases the side effects of methotrexate.
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