Taking Ibuprofen With Methotrexate

Min asked

I use methotrexate and want to know about 800mg of ibuprofen. Also, is it OK to take tramadol 100mg too?

Answer

Methotrexate does have fairly significant interaction with ibuprofen, but they are often used together.

Although this sounds somewhat confusing, in most cases, your dose of methotrexate will determine whether or not it is safe to use a pain reliever like ibuprofen. Clinically concerning interactions occur, in general, only when high doses of methotrexate are used.

Methotrexate - Ibuprofen Interaction

Ibuprofen is classified as a Nonsteroidal anti-inflammatory drug or 'NSAID'. Other commonly used NSAIDs include:

• Aleve (naproxen)
• Celebrex (celecoxib)
• Mobic (meloxicam)
• Voltaren (diclofenac)
• Dolobid (diflunisal)

In general, NSAIDs like ibuprofen decrease the elimination of methotrexate from the body, which can increase overall blood concentrations. Increased methotrexate concentrations can greatly increase the risk of severe side effects, including bleeding and gastrointestinal toxicity.

NSAIDs can decrease methotrexate elimination by:

• Displacing it from blood proteins, increasing concentrations in the blood.
• Inhibiting prostaglandins, which could lead to reduced kidney function.
• Decreased kidney tubular secretion.

High Dose Methotrexate And NSAIDs

As mentioned, the interaction between NSAIDs and methotrexate is more severe when high doses of methotrexate are used. High doses of methotrexate are used for the treatment of a variety of conditions, including:

• Neoplastic diseases (e.g. breast cancer, non-Hodgkin’s lymphomas)
• Psoriasis

The prescribing information for methotrexate warns explicitly against the use of NSAIDs when you are taking high doses of the drug:

"Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity."

Low Dose Methotrexate And NSAIDs

A low dose of methotrexate (7.5 to 20 mg per week) is a recommended first‐line drug for the treatment of rheumatoid arthritis, a chronic, auto-immune joint disease.

Although there is some controversy regarding just how much safer NSAIDs are with low-dose versus high-dose methotrexate, low doses do appear to cause fewer side effects and toxicity.

The prescribing information for methotrexate only recommends 'caution' with low-doses:

"Caution should be used when NSAIDs are administered concurrently with lower doses of methotrexate. In patients with rheumatoid arthritis, methotrexate has been given concurrently with NSAIDs without apparent problems. It should be noted that the doses of methotrexate used in rheumatoid arthritis are lower than those used in psoriasis or malignant disease; higher methotrexate doses may lead to unexpected toxicity in combination with NSAIDs."

Most studies that evaluate the beneficial effects of methotrexate in the treatment of rheumatoid arthritis do so in patients that are taking NSAIDs as well, and reports of significant side effects are uncommon.

Nevertheless, some new studies, such as one published in 2018 in the journal 'Pharmacoepidemiology and Drug Safety' conclude that low-dose methotrexate and NSAIDs are associated with a significantly increased risk of serious adverse events, so further study is clearly warranted.

Methotrexate With Tramadol

Tramadol does not interact with methotrexate or ibuprofen and would be safe to take with them.

However, tramadol, an opioid analgesic, and controlled substance, is generally only recommended to take on a short term basis. Additionally, its use isn't generally recommended in any guidelines for the treatment of rheumatoid arthritis.

The American College of Rheumatology guidelines don't mention opioids at all and the NICE UK guidelines state the following:

"There was limited evidence on paracetamol [acetaminophen], opioids and tricyclic antidepressants and no evidence for nefopam, gabapentinoids or selective serotonin reuptake inhibitor (SSRI) and SSNRI antidepressants. The committee acknowledged that the 2009 guideline had recommended analgesics other than NSAIDs for pain control. However, the 2009 guideline indicated that the evidence on analgesia other than NSAIDs was ’sparse’. No further evidence on these drugs was identified since the publication of the 2009 guideline."

Nevertheless, if your doctor has prescribed tramadol to take intermittently for the pain from RA, or for other indications, it is considered safe with ibuprofen and tramadol.