Methotrexate (Rheumatrex®)

Methotrexate is used to treat rheumatoid arthritis, myositis, lupus, psoriatic arthritis, other forms of inflammatory arthritis and vasculitis, including giant cell arteritis.

The way the drug works isn’t certain, but it has anti-inflammatory effects and modulates the immune system.

Generic methotrexate comes in 2.5 mg tablets, plus a liquid that can be given as a shot under the skin or taken with juice by mouth. The usual dose of methotrexate is 10 mg to 25 mg once a week. For example, if you are taking 15 mg per week, that would be six tablets per week. The tablets are taken all on one day. They can be taken together all at once or spread out over the day. Your doctor probably will start you on a low dose of methotrexate initially and increase the dose at intervals, depending on your condition and response. It is very important to follow dosing instructions carefully.

The liquid form of methotrexate is available at a concentration of 25 mg/mL. It is yellow. The liquid form can be useful for patients who can’t absorb methotrexate orally or have gastrointestinal side effects such as nausea. If you are taking methotrexate liquid subcutaneously, each 0.1 mL equals 2.5 mg. For example, 0.8 mL equals 20 mg of methotrexate.

If you are prescribed methotrexate liquid, you also will receive 1 mL tuberculin syringes to draw up the appropriate amount. Sites for subcutaneous injection include the abdomen, thighs, and shoulder. An area of skin is pinched and entered at a 45-degree angle quickly, then injected. Generally, there is minimal discomfort with this. Our nurses also are knowledgeable on this technique and can teach you the proper way to inject.

A vitamin called folic acid is prescribed at 1 mg per day, and this helps prevent or lessen many side effects of methotrexate.

In general, methotrexate is very well tolerated, but there are potential side effects. Pregnancy should be avoided while on methotrexate and not be attempted until you have been off the drug for several months, because of the risk of birth defects. Adequate birth control methods are recommended. Men should be off methotrexate for about three months before attempting to conceive.

Other potential side effects from methotrexate include:

• fatigue (tiredness)
• flu-like symptoms
• upset stomach
• headaches
• mouth sores
• elevated liver blood tests
• lowering of the red cell (anemia) or white cell (infection fighting) counts
• increased risk of infections

There is an increased risk for liver and blood problems if you:

• do not take folic acid
• are overweight
• drink alcohol heavily
• have diabetes
• have kidney problems or liver problems

We recommend that alcohol use be minimized while on methotrexate. An occasional glass of wine or beer probably is acceptable, but heavy alcohol use has been associated with cirrhosis when used with methotrexate. There is a very small risk of cirrhosis from methotrexate, even when not used with alcohol.

Another extremely rare complication of methotrexate is a type of pneumonia not caused by an infection, but as a reaction to the methotrexate. For this reason, if you develop a cough or fever, stop the methotrexate until the symptoms subside. If the cough returns whenever you start the methotrexate, the problem could be from methotrexate and notify your rheumatologist. However, most patients develop a cough once or twice a year from viral infections, and this is usually not due to methotrexate.

Methotrexate sometimes causes a rash with lots of sun exposure, so wear sunscreen if you’re going to be in the sun.

Methotrexate generally begins to take effect after four weeks, reaching maximum effect after three to five months. Not everyone responds to methotrexate optimally, and your doctor may discuss adding other medications, if necessary. Because it is a slow-acting medicine, stopping the dose for a week or two if you have an infection or require surgery, does not usually result in a flare-up of symptoms. Only if the medicine is stopped for several weeks, do symptoms usually start to recur.

Before starting methotrexate, you will need to have a baseline complete blood count (CBC) and liver test (ALT). One month after starting methotrexate, these labs are repeated to make sure your body is tolerating the medicine. After that, the blood tests are checked every two months.

Abnormal labs may necessitate dose adjustments or more frequent lab tests. If you have several consecutive normal labs, sometimes the interval for labs can be extended to every three months. If multiple abnormal liver tests occur, liver biopsy might be required, but this is very uncommon.

If you have any infection more serious than a cold or bladder infection, it is a good idea to stop methotrexate for a week or two until you’re better. Also, it is fairly standard to stop methotrexate the week before and the week of a significant surgery. There is an interaction between methotrexate and sulfa antibiotics, such as trimethoprim/sulfamethoxazole (Bactrim/Septra). These antibiotics are commonly used to treat bladder infections. Usually, these antibiotics are avoided while on methotrexate, although a short, three-day course may be acceptable.

Pharmacists sometimes tell patients about adverse interactions when methotrexate is taken with NSAIDs (nonsteroidal anti-inflammatory drugs), such as ibuprofen. These concerns are applicable mainly with very high doses of methotrexate or in the presence of kidney failure, so are not of great concern to most patients.