Part 3: Methotrexate Side Effects in Rheumatoid Arthritis Patients

What about methotrexate side effects often means, “What can methotrexate do to me?”

Although methotrexate is often the first DMARD (disease modifying anti-rheumatic drug) which is prescribed to treat Rheumatoid Arthritis, it is still considered a dangerous drug. It is used as chemotherapy for many cancers, but in much higher doses than it is to treat RA. It is sometimes also used to cause medical abortion, as for ectopic pregnancies. It’s not cotton candy, in other words. It is a toxic substance.

The most commonly reported side effects for the RA-sized doses are digestive irritations. This can range from mild nausea to severe vomiting and diarrhea. Hair loss is also possible, but with lower doses it is less common. Methotrexate can also cause a feeling of weakness which is referred to medically as malaise. I call it that “I’ve been kicked by an elephant” feeling. (I really was kicked by an elephant once… but that’s another story!)

Other common side effects of methotrexate include increased risk with infection and greater chance of sunburn, either of which may also be more severe with methotrexate. For a very detailed list of methotrexate side effects, see this page on Drugs.com. They have information on all of the body systems which can be affected by this drug. Drugs.com has even sorted out the side effects for treatment of Rheumatoid Arthritis (as opposed to cancer treatment with higher doses).

The most serious side effect which RA patients are likely to experience is one that could go unnoticed by them, at first. It is liver damage. Methotrexate can lead to liver cirrhosis or liver fibrosis. Long term use can also cause liver toxicity. For this reason, rheumatologists usually require patients to submit to regular tests of liver function. This is a simple blood test, usually run every 6-8 weeks. This way, any indication of liver reaction will be recognized early when the problems are likely reversible.

What causes methotrexate side effects?

Methotrexate works by interfering with folate at the cellular level. That is why it is also called a “folate antagonist”. It has lots of nicknames, huh? This impairing of folate is considered the reason for most of methotrexate’s side effects. However, nearly all of those side effects can be moderated by taking folic acid supplements. And amazingly, this does not interfere with the effectiveness of methotrexate in treating Rheumatoid Arthritis. The folic acid must be a prescription dose – it’s many times higher than the USRDA.

Drug interactions

Many drugs can interact with methotrexate. It can be absorbed at a different rate when mixed with other medications including certain antibiotics and NSAIDs (non-steroidal anti-inflammatory drugs which are used for pain relief). This can actually cause the methotrexate to be present at a higher or a lower concentration than intended.

The most important thing a patient can do about this risk is to inform and remind each of his doctors and pharmacists of every drug, supplement, and natural remedy which is being used. Sometimes, both drugs may still be able to be used if taken several hours or days apart. Or perhaps careful monitoring may make it acceptable.

Sometimes, if a drug is not compatible with methotrexate, it would be necessary to discontinue the other medication or switch it out for another one. While there are lots of antibiotics and many NSAIDs and herbal anti-inflammatories, there is only one methotrexate.

Personal aside

Well, methotrexate side effects do sound harsh, don’t they? However, when was the last time you read a list of the effects of RA? Seriously, the list of Rheumatoid Arthritis symptoms is eerily similar. For the most part, RA is undoubtedly worse.