Methotrexate acts as a folic acid antagonist, reducing DNA, RNA and protein synthesis and causing cell death. It is used in inflammation to reduce the proliferation of rapidly producing cells such as lymphocytes.
Oral, but parenteral routes can be used.
- Gastrointestinal upset
- Rash
- Myelosuppression
- Alopecia
- Cirrhosis
- Pulmonary fibrosis
- Renal impairment (high dose therapy)
Some of these symptoms can be reduced by co-administration of folic acid.
In overdose or toxicity, folinic acid may be used.
Aspirin and NSAIDs reduce the excretion of methotrexate and therefore can cause toxicity.
Other folate antagonists such as trimethoprim or co-trimoxazole should be avoided.
Methotrexate should not be used with ciclosporin.
Methotrexate does not cross the blood-brain barrier and thus needs to be given intrathecally if needed as part of a chemotherapy regime.
