Is Methotrexate Considered Chemotherapy?

Carol Eustice
·4 min read

Medically reviewed by Anita C. Chandrasekaran, MD

Methotrexate is known to be a chemotherapy drug used to treat several types of cancer. When used at higher doses, it helps slow the growth of cancer cells.

However, at lower doses, methotrexate is commonly used as a disease-modifying anti-rheumatic drug (DMARD) to treat autoimmune disorders like rheumatoid arthritis (RA). This is because of its anti-inflammatory properties. It has different mechanisms of action (how the drug works) for use in cancer versus autoimmune diseases like RA.

This article discusses the differences between using methotrexate as a chemotherapy agent and as a DMARD for rheumatoid arthritis.

Blend Images / Getty Images
Blend Images / Getty Images

Methotrexate as a Chemotherapy or DMARD

Methotrexate was first introduced in 1948 as a treatment for cancer. It works by slowing the growth of cancer cells in specific types of cancer, including:

Each cancer type has specific dosage guidelines.



Takeaway

When used as a chemotherapy agent, methotrexate prevents cells from using folate to make DNA and RNA, thereby slowing the growth of cancer cells.



The U.S. Food and Drug Administration approved methotrexate as a therapy for rheumatoid arthritis in 1988. Since that time, the drug has become a commonly used DMARD to treat RA and other autoimmune diseases.

Although methotrexate's exact mechanism in slowing RA is unclear, it appears to work by modulating adenosine signaling pathways (decreasing activity in the immune system).



Takeaway

To ameliorate the effect of methotrexate on folic acid production, daily supplementation with folic acid is part of the usual regimen for rheumatic disease patients.



The popularity of DMARDs for the treatment of RA is due to several factors:

  • Ease of use (oral or injectable, weekly dosing)

  • Well-defined toxicities

  • Rapid onset of beneficial effects (usually within six to eight weeks)

  • Durability (a drug's ability to postpone disease progression in a safe and well-tolerated way)

  • Low cost

  • Additive benefits, when combined with other DMARD regimens

  • Ability to slow RA damage

Related: What to Know About DMARDs for Rheumatoid Arthritis

The central difference between using methotrexate as chemotherapy and using it as an immunosuppressant to treat autoimmune conditions comes down to dosing.

Methotrexate Dosing: Chemotherapy vs. DMARD

When used as a chemotherapy drug, methotrexate is given in intermediate to high doses. The dose is determined by the patient's size, the type of cancer being treated, and kidney function. Doses greater than or equal to 500 mg/m2 are considered high, while doses 50 to 500 mg/m2 are intermediate. A low dose is considered under 50 mg/m2.

When methotrexate is used to treat rheumatoid arthritis, the once-weekly dose is considered low—usually starting at 7.5 to 10 mg/week. If needed, the dose can be increased incrementally up to a maximum of 25 mg/week.

Side Effects of Methotrexate

Chemotherapy

Common and severe side effects are possible when using methotrexate as a chemotherapy agent.

Common side effects include:

  • Diarrhea

  • Upset stomach

  • Vomiting

  • Mouth sores

  • Hair loss (relatively uncommon)

  • Fatigue

Severe side effects can include:

  • Bone marrow problems

  • Kidney problems

  • Liver problems

  • Lung problems

  • Stomach or bowel problems

  • Skin reactions

  • Infections

Some severe side effects may not go away and can be deadly.

DMARD

Common side effects of using methotrexate as a DMARD include:

  • Gastrointestinal problems such as nausea, vomiting, or stomach pain

  • Mouth ulcers or sores

  • Headaches

  • Dizziness or fatigue (sometimes called “methotrexate fog”)

  • Hair loss (relatively uncommon)

If side effects or toxicities do develop, dose reduction or a switch from oral to injectable methotrexate may manage the issues.



RA Side-Effect Prevention Tips

Most common side effects can be lessened by supplementing with folic acid, reducing or splitting the dose of oral methotrexate (or switching to injections), using an anti-nausea medication, and rinsing with salt water or a pain-relieving mouthwash.



Routine blood tests are performed on all patients taking methotrexate, either as chemotherapy or to treat RA. Complete blood count as well as liver and kidney profiles detect problems early so that adjustments can be made.

If rare, serious adverse events develop, discontinuation of methotrexate is necessary.

Summary

While methotrexate in high doses may be used for chemotherapy, rheumatologists use low-dose methotrexate to treat autoimmune conditions, like RA. When used for RA, the drug is taken only once per week to limit potential side effects. Methotrexate's side effects can be serious when it is taken in high doses but, are generally manageable and modifiable when taken at the lower doses used to treat RA.

Read the original article on Verywell Health.