Expert Q&A: Methotrexate Shot or Pills

When methotrexate pills aren’t effective enough, injections are one alternative.

Q: Is there any benefit to receiving methotrexate by injection as opposed to taking it orally? Is it metabolized differently? Are the side effects of methotrexate injection different?

A: Methotrexate is a disease-modifying antirheumatic drug (DMARD) used to slow the disease process and treat the pain and swelling of rheumatoid arthritis and juvenile idiopathic arthritis as well as the skin disease psoriasis.

In general, methotrexate is used as an oral agent in doses up to 25 milligrams per week. The body's absorption of the drug, and therefore its effectiveness, varies among individual patients when it is taken orally.

If a patient’s response to the oral formulation is not considered adequate, there are various alternative approaches, depending on the patient, provider and insurer, such as trying a different medication. Another alternative is simply to switch from oral methotrexate to the injectable formulation, which can increase blood levels of the drug and improve responses.

The potential side effects and benefits of methotrexate are virtually the same whether it is given orally or by injection. Liver damage with long-term use of methotrexate remains the main concern, and it may differ with RA and psoriasis. It is monitored by blood tests. Taking 1 mg of folic acid per day can help reduce other side effects related to methotrexate use, such as mouth sores or gastrointestinal irritation.

David Pisetsky, MD, PhD
Rheumatologist and Immunologist
Duke University Medical Center

Last reviewed 4/14/2021

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