Drug Breakdown: Methotrexate

Dr Sharon Rees @reesprescribe

Day 1: In the 1950s, designing a folate analogue was an anti-cancer strategy. Used at high levels, the good tolerability of #methotrexate and the option of folinic acid rescue if bone marrow toxicity occured was considered advantageous. #methotrexate was FDA licensed in 1953.

Dr Sharon Rees @reesprescribe

(cont) However, a role for #methotrexate in rheumatoid arthritis was slow to emerge, as sulfasalasine and gold were preferred agents. Considerable evidence supports #methotrexate ef~ cacy as a disease modifying anti-rheumatic drug, a lot of which emerged in comparison trials with newer biologic agents.

Dr Sharon Rees @reesprescribe

Day 2: There is now considerable evidence to support #methotrexate is now well-established as the 1st line immune-suppressive drug for rheumatoid arthritis (RA), being effective and relatively cheap. Also used for flare & remission of Crohn's disease and severe psoriasis. The weekly dose is mostly oral 7.5-25mg (typically 7.5–15mg for RA).

Dr Sharon Rees @reesprescribe

Day 3: Mechanism of action – Nucleotide synthesis is necessary for RNA and DNA production. #methotrexate inhibits multiple enzymes required for the process, hence exerts anti-inflammatory, anti-proliferative and cytotoxic effects.