Living with Lupus

Methotrexate (Rheumatrex) for Lupus

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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 arthritis. It is not specifically approved for lupus, but data suggests that it’s one of the top immunosuppressants prescribed.

Type: DMARDs

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.

Brand names:

Rheumatrex Dose Pack; Trexall


Need-to-Know Methotrexate Info

  • Methortrexate is usually taken once or twice per week. NOT everyday. 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
    • pneumonia
    • lung disease
    • are receiving radiation treatments


The methotrexate tablets label information from the FDA is available here.

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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
  • fever
  • dizziness
  • diarrhea
  • vomiting
  • hair loss (often hair grows back when the medication is stopped)
  • bruising
  • 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)

Drug interactions

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)
  • phenylbutazone
  • phenytoin (Dilantin)
  • sulfonamides (Sulfatrim, Bactrim)
  • oral anibiotics (tetracycline, chloramphenicol, broad spectrum antibiotic)
  • penicillins
  • 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.


Other interactions


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.



Methotrexate is a relatively cheap medication. GoodRX makes the following price estimates for methotrexate:

24 tablets of 2.5mg methotrexate:

Average cash price: $74.45

GoodRx Fair Price: $35.59


Lupus & methotrexate research

While lupus is not specifically approved for lupus, there have been a large number of studies that intend to measure the effectiveness of the drug for people with lupus. Some studies are quite specific, finding benefit of methotrexate for people with cutaneous lupus, antimalarial-resistant lupus arthritis, and mucocutaneous features.


Study review:

Methotrexate in systemic lupus erythematosus: a systematic review of its efficacy (2014)

Included studies:

Of 53 potential studies, only nine were eligible for inclusion by the authors (3 randomized controlled trials and six observational studies).

Significant Findings:

SLEDAI scores: Participants taking methotrexate had significantly less disease activity (p = 0.001)

Corticosteroid use: Participants on methotrexate were able to take significantly lower doses of corticosteroids (p = 0.001)



Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus


41 patients began study; 37 completed the 6 month study (2 placebo patients dropped out due to severe flares. 2 methotrexate patients dropped out — one due to pulmonary tuberculosis and the other because of urticaria and severe dyspepsia). Average SLE duration was 82.5 months.

Participants received either a placebo or 15-20 mg/week of methotrexate for six months.

Significant Findings:

Articular (joint) complaints: 16 placebo participants had joint complaints compared to 1 methotrexate participant (p < 0.001).

Hypocomplementemia (decreased complement levels in the immune system): 11 placebo participants compared to 4 methotrexate participants (p < 0.001)

Average SLEDAI scores: Significantly higher, suggesting higher disease activity, for participants receiving the placebo, at months 3, 4, 5, and 6.

Decreased prednisone dose: 1 placebo participant reduced prednisone dose compared to 13 methotrexate participants (p < 0.001). This finding of decreased steroid use was confirmed in other studies of people with moderately active lupus.

Side effects: 14 methotrexate participants (70%) experienced side effects – most experienced were dyspepsia and increased hepatic enzyme serum levels. 3 placebo participants experienced dyspepsia. These side effects were considered mild.


Additional research examined how well methotrexate was tolerated and the frequency of side effects.


Methotrexate use in systemic lupus erythematosus


101 participants with SLE. 24 participants were treated with methotrexate during 25 treatment episodes (one person was taken off the medication and began it again.)

The median duration of methotrexate treatment episode was 14.4 months (range 5.1 months to 41.6 months).

The median initial methotrexate dose was 7.5 mg/wk (range was 2.5 mg/wk to 10 mg/wk). The median peak dose was 10 mg/wk (range 7.5 mg/wk to 15 mg/wk).


This study found moderate, but not statistically significant decreases in steroid use when taking methotrexate.

2 participants terminated methotrexate as a result of toxicity.

The probability of continuing treatment at 12 months was 68%.

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