Rheumatoid Arthritis

What Are the Side Effects of Methotrexate For RA?

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Over the last quarter of a century, doctors and scientists have been working to find a way to effectively treat the devastating and life-altering symptoms of Rheumatoid Arthritis (RA).

Methotrexate (also known as its abbreviated form, MTX) is one of the most popularly prescribed pharmaceuticals for RA and has been at the forefront of treatment methods since it was first created in 1947.

While it has been shown to be effective for some people, there are several common side-effects of MTX that those who take it to treat their RA symptoms should be aware of.

What is Rheumatoid Arthritis?

Rheumatoid Arthritis (RA) is an autoimmune disease that has no known cure, and scientists are not even really sure what precisely causes RA to occur.

As Josef Smolen and Edward C. Keystone write, RA is an extremely active disease that causes serious issues with the joints in the body and can ultimately become disabling for those who have it, even in spite of treatment efforts.

It is estimated that about 1.5 million Americans suffer from RA.

This autoimmune disease tends to occur more frequently in women and manifests most predominantly between the ages of 30 and 60.

Your body’s immune system is responsible for fighting off harmful invaders. However, when you have an autoimmune disease, the immune system mistakenly attacks organs and tissues within the body.

With RA, as the Arthritis Foundation claims, the immune system mistakenly attacks the joints.

As Jim Morelli of CNN reports in this YouTube clip, RA can have devastating effects and even lead to patients needing to undergo joint replacement procedures.

When this happens, the synovial membrane that surrounds and protects your joints becomes enlarged and swollen, leading to the sensation of joint pain.

Most of this pain is allocated in the joints of your fingers, hands, elbows, knees, ankles, and feet. Also, the pain tends to affect both sides of the body.

How Does Methotrexate Work, and Which Nutrients Does It Affect?

As Dr. Michael E. Weinblatt reminds us, MTX is an extremely common pharmaceutical drug used the world over to treat symptoms of RA.

MTX is classified as an antimetabolite, which is a fancy way of saying that this is a drug that interferes with your body’s normal metabolic process. It can be orally taken as a pill or administered via an injection from your doctor.

MTX was originally created as a way to stop cancerous cells from metastasizing by restricting their access to the one crucial B vitamin that they need to survive, folate.

According to the National Institutes of Health, the body normally has about 10 to 30 mg of its own folate at any given time, which is found in the liver, tissues, and bloodstream.

Folate is necessary to have in your body because of its ability to make and repair DNA and to create red blood cells (RBCs).

A folate deficiency (whether it is due to taking MTX, experiencing nutritional malabsorption, or some other cause) can lead to symptoms such as oral sores and swelling, fatigue, graying and thinning of the hair, feeling irritable, and experiencing a shortness of breath.

Many of those who take MTX are at risk for developing a folate deficiency and are often encouraged to take folate supplements, which can be purchased over-the-counter.

Folate can also be supplemented by eating folate-rich foods, such as avocado, okra, and asparagus.

Common Side Effects of Methotrexate

As Timothy Gower writes, a 10 to 25 mg dosage taken every week is considered standard for those with RA while those who are taking it to treat cancer or leukemia will take exponentially higher dosages.

Even at such a considerably small dosage, those with RA can experience side effects from taking MTX.

One of the most common side effects of MTX is inflammation and soreness in the lips, tongue, and mouth. As you might be able to guess, this is due to the folate deficiency that MTX causes in the body.

Additionally, you might notice hair loss, be thinning, or grayness due to the lack of folate in your body; while grayness will not reverse, you will likely notice hair re-growth at least six months to a year after stopping MTX or increasing your folate supplementation.

Other side effects can include nausea, vomiting, abdominal pain or cramping, and other gastrointestinal issues. Again, this might be due in part to the lack of folate and requires supplementation.

As Patil and others reveal in their study on vomiting and nausea in young people taking MTX, gastrointestinal intolerances are more common in adolescents and young adults, and there seems to be a correlation between age and duration of medication administration.

Other common side effects of MTX can include fatigue, experiencing blurred vision, experiencing bleeding gums, and having a low white blood cell count (also known as leukopenia).

These side effects tend to lead to the cessation of MTX treatment. In fact, a study conducted by McKendry and Dale illustrates that patients who have been taking MTX for 60 months or longer had a 75% rate of stopping their treatment, and eight of these 144 patients ended up developing serious leukopenia.

Serious Side Effects of Methotrexate

Even more serious side effects of MTX can occur. These side effects can include experiencing a shortness of breath, darkened urine (or the inability to urinate at all), stools that have a clay-like hue, and feeling as if you are sick with the flu. You might also experience a partial or complete loss of appetite.

There is also a chance of developing jaundice, which is a yellowing of the eyes and/or skin.

Jaundice in those with RA is typically caused by a depletion of red blood cells within the body, which is something that can result from taking MTX.

In addition to jaundice, you might also notice skin rashes or blisters starting to develop after you start taking MTX.

The higher the dosage you take, and the longer you take it for, the more likely it is that you will develop at least one serious side effect.

This seems to be especially true for patients who are being treated for juvenile rheumatoid arthritis.

Additionally, it is possible for people to have allergic reactions after taking MTX. If you find yourself breaking out into hives, feeling any area of your face immediately swell up, or are having difficulty breathing, you need to seek emergency medical attention straight away.

Methotrexate Drug Interactions

Before you take your first dosage of MTX, you should be aware of which pharmaceuticals it is known to negatively interact with.

These drugs include the following:

  • Retinol
  • Azathioprine
  • Tetracycline
  • Chloramphenicol
  • Tretinoin
  • Hydroxychloroquine
  • Isotretinoin
  • Theophylline
  • Sulfa drugs
  • Steroids
  • Orally-ingested diabetes medications
  • Phenytoin
  • Probenecid
  • Gold treatments
  • Acid reducers
  • Penicillin
  • Aspirin and other salicylates
  • Non-steroidal anti-inflammatory drugs (NSAIDs)

Your doctor should be aware of the medications you take before prescribing you MTX.

If you are worried that MTX could interact with something that you are already taking, you need to speak with your doctor to address the issue, as reactions to these drug mixtures range from mild to (in the rare case) extremely severe.

What To Do When Side Effects Occur

When prescribing MTX, your doctor and/or pharmacist should issue you instructions on what you should do in case of side effects manifest.

If they do not do so, and you believe you are experiencing negative side effects due to MTX, you need to call your doctor and seek their advice.

Some people will stop cold turkey, which, according to Dr. Alan Matsumoto, will not present a problem for some individuals.

However, those with ongoing active RA could potentially experience a flare-up after suddenly stopping treatment with MTX.

You can reduce the impact of side effects in several ways. The first is by working your weekly MTX dosage around your schedule.

For example, you can take MTX on a day when it will not affect your performance at work or school.

You should also consider taking MTX at dinner, which restricts any minor negative side effects to the nighttime.

If you are experiencing oral sores or swelling, you might want to consider getting the injection versus taking the pills.

Also, folate supplements should, under the watchful eye of your rheumatologist, be added to your daily intake.

Should you test low for RBCs, it is important that your doctor is made aware of this issue and that you reduce your alcohol consumption, as alcohol can further compound the problem.

Keeping up-to-date on your blood levels is crucial when you are dealing with an autoimmune disease like RA.

A diagnosis of Rheumatoid Arthritis is not a death sentence, but the side effects you can get from taking Methotrexate might make you feel more unwell.

While MTX has shown to be effective for many with RA, it does not work the same for everyone.

Alert your doctor to any issues you experience while taking MTX, but do not give up hope for finding a way to alleviate your joint pain.

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