Methotrexate-Based Drugs Linked to Skin Cancer

In a recent study, researchers found that the drug methotrexate may increase the risk for skin cancer as well as other adverse side effects such as gastrointestinal complications and lung problems.

What is methotrexate?

Methotrexate-based drugs are immunosuppressants which help treat inflammatory conditions such as rheumatoid arthritis (RA). The Johns Hopkins Arthritis Center estimates that about 60 percent of rheumatoid arthritis patients are currently using or have used these medications. Methotrexate-based brands include Otrexup, Trexall, and Xatmep.

methotrexates skin cancer

What does methotrexate treat?

In addition to RA, methotrexate is utilized to treat psoriasis, which causes skin inflammation. It does this by slowing skin cell growth to prevent scale formation. Methotrexate is also used to treat various cancers including lung cancer, breast cancer, certain head and neck cancers, certain kinds of lymphoma, and leukemia. It treats cancer by slowing cancer cell growth.

How is it administered? What is the right dose? 

Methotrexate can come in either the form of a 2.5-milligram pill or an injection. The recommended dose is once a week. The typical dosage ranges from 3 to 10 pills. However, the individual dose may be split into two or more to avoid side effects and facilitate absorption. Methotrexate may sometimes be administered through escalating doses. For instance, one may take three tablets once a week for a two-week period and increase the dosage to four tablets starting in the third week.

What are some of methotrexates’ side effects? 

These are some of methotrexate’s side effects:

  • Drowsiness
  • Headaches
  • Dizziness
  • Decreased appetite
  • Hair Loss

More severe side effects include

  • Blurred vision
  • Sudden vision loss
  • Seizures
  • Difficulty with moving one or both sides of the body
  • Loss of consciousness
  • Birth defects in children of individuals, both men and women, who are taking it.

Methotrexate Study Results

The results of the study raising concerns about the safety of methotrexate were published in March 2020 in the Annals of Internal Medicine.  The study was a randomized trial comprised of over 6,000 patients. Each of them had a prior history of heart disease or diabetes. The average age of the patients was 66 years. The researchers gave patients either a low-dose methotrexate or a placebo. All the patients also took a one-milligram dose of folic acid on a daily basis. The researchers tracked the test subjects for about 23 months.

The results showed that 87% of patients who received methotrexate-based drugs suffered an adverse health effect, compared to only 81% of patients who received a placebo. Compared to the placebo group, patients taking methotrexate showed a 50% higher risk for skin cancer, 91% for gastrointestinal issues, 50% for lung complications, and 15% for blood-related conditions. Interestingly, the researchers found that methotrexate reduced the risk of renal adverse effects. They also found no increased risk for other cancers.

Institute for Safe Medication Practice Report

In December 2019, the Institute for Safe Medication Practice published a report in which researchers found that patient error when taking the wrong methotrexate dosages was very common. They found that six out of fourteen cases involving accidental daily use of methotrexate involved patient error. The cases involved patients over the age of 65. Older individuals usually take medications daily and may struggle to properly read instructions found on labels. The researchers found that the instructions were confusing. This means a misread of the instructions can be dangerous. They note that the risk was worse if the directions that involve escalating doses. There was one such case of this confusion, which resulted in the patient being hospitalized with hypotension, pancytopenia, and septic shock within five days of taking the medication.

The report also noted that the methotrexate usage nearly doubled from about 560,000 to 1 million patients between 2013 and 2017. This is concerning because more patients may experience these side effects. The study showed that individuals can easily take the wrong doses, which means that more individuals experience methotrexates’ harmful side effects.

Can Methotrexate Cause Cancer?

It may be that methotrexate could make it more likely that you could get some types of cancer, especially skin cancer.  There also could be a risk of non-Hodgkin’s lymphoma and lung cancer. 


The results of these recent studies may signal tough times ahead for methotrexate drugs.  Even smaller doses of methotrexate can increase adverse health effects. At a minimum, these results will probably lead to more in-depth studies about the link between methotrexate and skin cancer as well as other health conditions. This could potentially lead to future litigation.

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