Are Aspirin and NSAIDs Safe When Taking Methotrexate?

Medically Reviewed By William C. Lloyd III, MD, FACS
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If you have psoriatic arthritis, you may have been prescribed a disease-modifying antirheumatic drug (DMARD). These drugs are important because they can slow or even prevent long-term joint damage. Unfortunately, DMARDs don’t always reduce day-to-day joint pain. In that case, taking an aspirin or other nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen or naproxen at the same time may be an option. But is it safe?

There has been conflicting advice about taking NSAIDs and DMARDs at the same time. Some experts believe that NSAIDs prevent the body from ridding itself of DMARD toxins, increasing the risk for organ damage and other side effects. However, a new large-scale review of studies involving people who take the DMARD methotrexate found that most NSAIDs are safe to take at the same time for pain relief.

Researchers reviewed a total of 17 different clinical studies, which included more than 1,800 people who took methotrexate. The researchers compared the subjects’ side effects and complications based on NSAID use. All the participants had rheumatoid arthritis, which is an inflammatory arthritis similar to psoriatic arthritis.

Most NSAIDs Seemingly Safe

The researchers found that when taken with methotrexate, most NSAIDs did not increase the risk for lung damage. This includes aspirin taken at normal levels. The research also showed that the people who took NSAIDs, including aspirin, did not stop taking methotrexate because of increased side effects.

High Aspirin Intake Linked to Side Effects

However, the review also found that high doses of aspirin could cause kidney or liver problems if taken at the same time as methotrexate. High doses of aspirin were estimated to be about 2.1 grams a day, which is close to seven tablets of aspirin at 300 mg each. High doses of aspirin may be prescribed to reduce inflammation.

Ask Your Doctor

Although the study did not look at the effects of drug use among those with psoriatic arthritis or study all DMARDs available, it offers valuable information to discuss with your doctor. Potential side effects are a risk with any medication and must be weighed against possible benefits. These important decisions must be personalized so as to reflect the individual patient's overall health and risk factors. By working with your doctor, you can find a safe drug combination that protects against joint damage as well as reduces your joint pain

Key Takeaways:

  • Some experts believe that NSAIDs prevent the body from ridding itself of DMARD toxins, increasing the risk for dangerous side effects.

  • However, a new review of studies involving people who take the DMARD methotrexate found that most NSAIDs are safe to take at the same time for pain relief.

  • The review also found that high doses of aspirin could cause kidney or liver problems if taken at the same time as methotrexate.

Your doctor can help you find the right drug combination to protect against joint damage and reduce your pain. 

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  1. Colebatch AN, et al. Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). Cochrane Database System Review. 2011;(11):CD008872.
  2. Systemic Medications: Methotrexate. National Psoriasis Foundation. https://www.psoriasis.org/about-psoriasis/treatments/systemics/methotrexate
Medical Reviewer: William C. Lloyd III, MD, FACS
Last Review Date: 2022 Aug 11
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