Methotrexate (MTX) is a chemotherapy drug and immune system suppressant designed to treat cancer.
Methotrexate is a medication that interferes with the growth of rapidly reproducing cells in the body. This includes cancer cells, bone marrow cells, and skin cells.
An early variation of the drug, aminopterin was initially developed in 1947 by researchers led by Sidney Farber. It was a chemical analog of folic acid.
Methotrexate, proposed as a treatment for leukemia in 1950, was a further variation on folic acid. The medication was proposed as a treatment for leukemia and, by 1956, was found in animal studies to be more effective than aminopterin. Additionally, Jane C. Wright showed that methotrexate had benefit in reducing solid tumors, and showing remission in breast cancer.
In the late 1980s, methotrexate was approved by the FDA for rheumatoid arthritis. For over three decades, it has been a staple of RA treatment
Methotrexate is known as a DMARD or Disease-Modifying Antiheumatic Drug. These are immunosuppressive medications that treat pain and swelling. These medications also decrease the longterm damage to joints.
Rheumatrex Dose Pack; Trexall
Need-to-Know Methotrexate Info
- Methortrexate is usually taken once or twice per week. The medication should be taken as prescribed by a clinician. Some people have died from taking methotrexate everyday by accident.
- Do NOT use methotrexate if you are pregnant or breastfeeding.
- Men and woman should use birth control to prevent pregnancy while on the medication as methotrexate use by either partner may cause birth defect.
- Do NOT use methotrexate if you have liver disease (especially if it is caused by alcoholism) or a blood cell/marrow disorder.
- Tell your doctor if you have any of the following:
- kidney disease
- a folate deficiency
- any infection
- stomach ulcers
- lung disease
- are receiving radiation treatments
Side effects of methotrexate
Most people taking methotrexate at low doses do not experience side effects and the side effects that are experienced often decrease over time.
Methotrexate can cause serious and even life-threatening side effects including:
- birth defects and death of unborn children
- serious anemia (a lack of red blood cells and/or hemoglobin in the blood that causes weariness)
- lower white blood cell counts
- liver damage
- kidney damage
- lung disease
- cancer of the lymph system (lymphoma)
- severe skin reactions/rashes
- infections such as pneumonia
- soft tissue and bone damage
Additionally, there are less serious, more common side effects including:
- mouth sores
- nausea or upset stomach
- feeling tired
- having the chills
- hair loss (often hair grows back when the medication is stopped)
- sun sensitivity
Talk to your doctor immediately if you have diarrhea, mouth sores, a fever, dehydration, cough, bleeding, shortness of breath, infection, or a skin rash.
An additional list of side effects is available here.
Laboratory tests for starting and using methotrexate
When using methotrexate, you should be closely monitored so that any toxic effects of the medication can be detected quickly.
Baseline assessments should be recorded including:
- a complete blood count with differential and platelet counts (CBC w/ Diff)
- hepatic enzymes
- renal function tests
- chest x-ray
During treatment for RA or psoriasis, the following parameters are recommended to be measured:
- hematology (at least monthly)
- renal function (every 1 – 2 months)
- liver function (every 1 – 2 months)
A total of 797 drugs are known to interact with methotrexate, including 188 major drug interactions. For a full list that can be easily searched, visit drugs.com.
Use of NSAIDs while using high doses of methotrexate has been reported to “elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity.” NSAIDs are common, over-the-counter pain medications that include:
- Aspirin (Bayer, Excedrin)
- Ibuprofen (Advil, Motrin)
- Naproxen (Aleve)
There are other NSAIDs, including some prescription versions. Be sure to speak with your doctor before using other medications with methotrexate. Despite this potential interaction, in RA patients receiving between 7.5 mg to 20 mg per week, the combination of NSAIDs and methotrexate have been used without issue. However, those dose is lower than in other condition areas.
Because methotrexate suppresses the immune system, speak with your doctor before receiving any vaccines you may plan to receive, including flu shots. The risk of opportunistic infections is high.
Other drugs can interfere with the absorption of the medication and increases the risk of hepatoxicity. The following common medications may also interfere with methotrexate dangerously:
- salicylates (Noxzema, Asepxia)
- phenytoin (Dilantin)
- sulfonamides (Sulfatrim, Bactrim)
- oral anibiotics (tetracycline, chloramphenicol, broad spectrum antibiotic)
- hepatoxins (e.g., azathioprine, retinoids, sulfa-salazine)
- etanercept (Enbrel)
- adalimumab (Humira)
With such a large list of potentially interfering medications, it is important to speak with your doctor before using any medication, even over-the-counter options or supplements.
Methotrexate may cause liver problems and you should avoid drinking alcohol while taking the medication.
Noted in patients taking methotrexate to treat arthritis, caffeine may reduce the effectiveness of the drug.
RA & methotrexate research
Methotrexate was approved by the FDA for the treatment of rheumatoid arthritis in 1988. Since then, it has become the “most popular drug worldwide for the treatment [of RA].”
A review published in 2013 explored the use of methotrexate over the last quarter of a century. The review explored placebo-controlled trials and the effect of long-term usage of the drug.
The author found that low-dose methotrexate, used by itself or in combination with other therapies, was more effective than other medications. Additional benefits were found when methotrexate was combined with biological therapies.
After using methotrexate for 1 year, 33% of people with RA had no progression of the disease as measured by radiography.
There have been studies supporting the use of methotrexate in RA in short, 18-week trials and longer studies. In one short-term trial, 32% of patients saw a 50% reduction in joint tenderness.
Measurable benefits were also found in longitudinal studies. Two studies looked at the benefits of methotrexate after an 11 year or greater period. These studies found clinical benefits that continued over time, known as sustained clinical response.
These findings of effectiveness over time and the safety profile of the mediation make it a powerful tool to help battle RA.