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Medications > Methotrexate > Methotrexate | Side Effects

Methotrexate | Side Effects

Methotrexate is a very commonly used medication to treat rheumatic diseases such as rheumatoid arthritis. It is generally a very safe medication that is tolerated by most patients who take it. You will read stories on the internet from people who hated taking methotrexate. Indeed there are some people who do not tolerate methotrexate but this isn’t the case for many people. Beware what you read on the internet!

With any medication used in rheumatology the goal is to reduce your pain, improve your function, and protect your joints from damage. In rheumatology, most medications take about 12 weeks to determine if they’re working. This is our first decision point. If it isn’t working at 12-weeks then there is no use continuing it. So, if you’re thinking of starting methotrexate, consider it a 3-month trial. If it’s working great at 3-months you’ll probably want to continue it, if it isn’t then you won’t.

Methotrexate can be taken by a small injection under the skin or by tablets. I much prefer the injectable form of methotrexate for a number of reasons:

  1. When taken by injection methotrexate is absorbed well (85%) and consistently. When taken by mouth, the absorption of methotrexate is much more variable anywhere from 20-80%.
  2. When taken by injection methotrexate has fewer side effects including nausea.
  3. There are a few small studies that show injectable methotrexate to be superior to oral methotrexate.
  4. Finally, it’s the only way I would give it to my own mother or myself and I’m a rheumatologist.

Remember when you’re injecting methotrexate it is just into the “fatty tissue” under the skin. You aren’t injecting it into a vein or other blood vessel. You can’t do anything wrong. Learn more about injecting methotrexate.

Ok, on to the side effects. The most common reason patients stop taking methotrexate is because they feel unwell after they take it (nausea). The nausea can improve over time but if it is intolerable you have to tell your rheumatologist (be honest). Lowering the dose or switching from the oral to injectable methotrexate can really help to reduce nausea. However, for some people, no matter the route of administration or the dose, methotrexate is not tolerated.

Methotrexate can also irritate the liver or lower the blood counts. In the doses it is used in rheumatology this isn’t an immediate serious concern but more of a long-term issue. This will be monitored through blood tests by your rheumatologist. Therefore, it’s important to have periodic blood testing (every month or two) while taking methotrexate. During an initial 3-month trial of methotrexate it would be extremely unusual for it to damage the liver or bone marrow.

As far as infections and methotrexate the risk isn’t really much higher than baseline. If you develop a fever, think you have an infection, or are prescribed antibiotics while taking methotrexate it is important to temporarily stop the methotrexate until you’re feeling better.

One of the very rare but serious side effects of methotrexate is an unusual lung reaction. In some people, methotrexate can cause “inflammation” in the lung tissue. The patient usually develops a dry cough (in the absence of a cold) or unexplained shortness of breath. The patient often feels unwell and may have a fever. This is more commonly seen in older individuals with underlying lung disease. If this happens it is important to stop the methotrexate right away and call your rheumatologist. It is often really tough to tell if the trouble is from an infection or due to the methotrexate.

At the doses used in rheumatology, methotrexate doesn’t cause a lot of hair loss but some people describe thinning of the hair. It also doesn’t cause many mouth sores but some people describe this as well.

Methotrexate is generally a safe and well-tolerated medication. However, we must respect all medications and be vigilant of their side effects.