Methotrexate myths and misconceptions

Providing accurate information to your patients about this antirheumatic drug will help them avoid potential nocebo effects

In an article written for the Medical Journal of Australia, University of Sydney physicians have outlined commonly held myths and misconceptions regarding methotrexate treatment for rheumatoid arthritis.

Methotrexate is a first-line agent and disease-modifying antirheumatic drug (DMARD). It made up about 20% of more than 3.4 million PBS-subsidised DMARD prescriptions between 2003 and 2007.

Led by rheumatologist Associate Professor Mark Arnold along with colleagues from the university’s Sydney Medical Program, the MJA article argues that misinformation regarding this important drug can generate nocebo effects and poor treatment adherence.

Here are some of the myths and misconceptions you may come across in your patients.


Methotrexate (for non-malignant diseases) is chemotherapy

For rheumatic diseases, methotrexate is typically used in low-dose weekly oral or parenteral regiments, in doses usually less than 10 mg/m² weekly. Meanwhile, in chemotherapy regimens where methotrexate may be used, single dosages might exceed 500 mg/m².

Methotrexate is unusual or strong treatment

Early treatment with methotrexate for rheumatoid arthritis is recommended by both the European League Against Rheumatism and the American College of Rheumatology. Research shows it is a safe and efficacious treatment that has been in use since the mid-1980s.

Patients should not be co-prescribed NSAIDs and methotrexate

Methotrexate is often prescribed along with NSAIDs or cyclooxygenase-2 inhibitors to achieve analgesic and anti-inflammatory effects in addition to the disease-modifying effect of methotrexate.

The authors point out there is a common automatic alert generated in prescribing software and pharmacies, which can lead to confusion for patients.

However, there are no specific grounds to unreservedly prohibit the combination of NSAIDs and methotrexate, they write.

In the context of compromised renal function, renal function should be monitored and the dose of methotrexate appropriately adjusted.

“Patients are often unnecessarily alarmed by advice from health professionals to avoid this drug combination at all costs, and this may contribute to the nocebo effect,” say the authors.

Third parties must avoid (any) exposure to the body fluids of methotrexate-treated patients

Patients may be told by health professionals or others to carefully dispose of their urine and faeces, avoid kissing, cuddling or nursing infants and children, and avoid both non-intimate and intimate kissing.

This is due to the myth of “methotrexate as chemotherapy” and the notion that “all cytotoxics are the same”. Normal standards of personal hygiene are the principal safeguard for third parties.

Patients receiving methotrexate should avoid contact with pregnant women

Methotrexate is a pregnancy category X drug (exposure to which has a substantial risk of causing permanent damage to the fetus) and should not be administered to pregnant women or those with reproductive capacity unless reliable contraception measures are employed.

However, the potential of a pregnant woman to have sufficient exposure to methotrexate from social contact with a methotrexate-treated individual with rheumatoid arthritis is negligible.

There is also a negligible risk in already pregnant women exposed to partners’ body fluids.


Methotrexate injections must be prepared by an oncology pharmacist and administered by an oncology nurse

Certainly methotrexate as chemotherapy must be prepared under this guidelines, but these do not refer to low-dose administration, say the authors.

“Methotrexate is neither a vesicant nor an irritant and is not an extravasation risk,” they add.

Eye, mask, glove and gown precautions are mandatory for staff administering injected methotrexate

Trace exposures could be anticipated through patients’ saliva, tears, urine or faecal material, but the practical likelihood that exposure resulting in toxicity is likely to be negligible, say the authors.

If staff are unwilling to administer injectable methotrexate to rheumatoid arthritis patients, self-administration should be recommended.

Self-administration is impractical and potentially unsafe

Self-injection can be safely recommended and instituted with appropriate education in rheumatoid arthritis patients treated with methotrexate, say the authors.

Methotrexate should not be administered by pregnant health care workers

Evidence shows there is no quantifiable reproductive risk to any worker or their partner from administering parenteral low-dose methotrexate to rheumatoid arthritis patients.

“To improve trust, patient engagement, treatment adherence and therapeutic outcomes, nocebo-generating notions regarding methotrexate should be discussed openly with patients at the initiation of and during treatment,” the authors conclude.

Read the original article here.

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  1. Harriet Wright

    Interesting that the use of NSAIDs and methotrexate is seen as normal practice here. I would always discuss this with a patient when they are on methotrexate. Wonder what my liability would be like if a patient had a problem taking NSAIDs and methotrexate and I hadn’t brought up this issue as recommended in the article.

  2. Debbie Rigby

    NSAIDs have no effect on the low doses of methotrexate used for rheumatoid arthritis

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