Most arthritis patients take methotrexate orally, in a dose consisting of several pills. Some find that splitting the dose eases GI side effects; take half the pills in the morning and the other half 12 hours later, preferably with food. What is Methotrexate? Methotrexate is a drug used to treat rheumatoid arthritis (RA) and and other inflammatory conditions. Nearly 60% of all rheumatoid arthritis patients are currently on or have been on methotrexate. Methotrexate is taken either as a tablet or given as an injection, especially if you have side effects with the tablets. It is also available as a liquid. Methotrexate for Your RA. Methotrexate is one of the most effective medications to treat rheumatoid arthritis (RA). It's the first drug most doctors prescribe after you’re diagnosed. 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 concise video discussing the medication methotrexate for the treatment of inflammatory arthritis such as rheumatoid arthritis. Methotrexate is an antimetabolite used in the treatment of certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. Chemically methotrexate is L-(+)-N-[p-[[(2,4-Diamino-6-pteridinyl)methyl]methylamino]-benzoyl]glutamic acid. USES: Methotrexate is used to treat certain types of cancer or to control severe psoriasis or rheumatoid arthritis. It may also be used to control juvenile rheumatoid arthritis.