Those individuals with rheumatoid arthritis treated with methotrexate have been found to have a lower risk of cardiovascular events such as myocardial infarctions (heart attacks) and strokes.Results of a systematic review exploring the comparative effectiveness of treatments of early rheumatoid arthritis can be improved with combination therapy of tumor necrosis factor (TNF) or non-TNF biologics with methotrexate alone.Likewise, a 2016 study found the use of methotrexate, in combination with anti-TNF agents, has been shown to be effective for the treatment of ulcerative colitis.Methotrexate has also been used for multiple sclerosis and is used occasionally in systemic lupus erythematosus, with tentative evidence to support such use. During pregnancy
Methotrexate is an abortifacient and it is used to treat ectopic pregnancies, provided the fallopian tube has not ruptured. Methotrexate with dilation and curettage is used to treat molar pregnancy. Rarely, it is used in combination with mifepristone to abort uterine pregnancies. Administration
Methotrexate can be given by mouth or by injection (intramuscular, intravenous, subcutaneous, or intrathecal). Doses are usually taken weekly, not daily, to limit toxicity. Routine monitoring of the complete blood count, liver function tests, and creatinine are recommended. Measurements of creatinine are recommended at least every two months. Adverse effects
The most common adverse effects include: hepatotoxicity (liver damage), ulcerative stomatitis, leukopenia and thus predisposition to infection, nausea, abdominal pain, fatigue, fever, dizziness, acute pneumonitis, rarely pulmonary fibrosis, and kidney failure.
Methotrexate is teratogenic and hence is not advised for either the prospective father to take it before or for the mother to take it before or during pregnancy (pregnancy category X) and for a period after birth. Methotrexate can also cause mucositis.Central nervous system reactions to methotrexate have been reported, especially when given via the intrathecal route (directly into the cerebrospinal fluid), which include myelopathies and leukoencephalopathies. It has a variety of cutaneous side effects, particularly when administered in high doses.Another little understood but serious possible adverse effect of methotrexate is neurological damage and memory loss. Neurotoxicity may result from the drug crossing the blood–brain barrier and damaging neurons in the cerebral cortex. People with cancer who receive the medication often nickname these effects "chemo brain" or "chemo fog". Drug interactions
Penicillins may decrease the elimination of methotrexate, so increase the risk of toxicity. While they may be used together, increased monitoring is recommended. The aminoglycosides, neomycin and paromomycin, have been found to reduce gastrointestinal (GI) absorption of methotrexate. Probenecid inhibits methotrexate excretion, which increases the risk of methotrexate toxicity. Likewise, retinoids and trimethoprim have been known to interact with methotrexate to produce additive hepatotoxicity and haematotoxicity, respectively. Other immunosuppressants like cyclosporins may potentiate methotrexates haematologic effects, hence potentially leading to toxicity. NSAIDs have also been found to fatally interact with methotrexate in numerous case reports. Nitrous oxide potentiating the haematological toxicity of methotrexate has also been documented.