Applies to methotrexate: compounding powder, injectable powder for injection, injectable solution, oral tablet
Hematologic
Hematologic side effects have included myelosuppression which is one of the primary toxic effects of methotrexate. Methotrexate suppressed hematopoiesis has been reported to have caused anemia, aplastic anemia, pancytopenia, leukopenia, neutropenia, thrombocytopenia, lymphadenopathy, and lymphoproliferative disorders including reversible hypogammaglobulinemia (which has been reported rarely).
Preexisting myelosuppression or low hematologic cell counts are contraindications to the use of this drug, particularly in patients with rheumatoid arthritis or psoriasis. Close monitoring of the CBC is mandatory. Profound count nadirs may require therapy discontinuation, at least temporarily. Folate therapy and/or leucovorin rescue may be preventive or palliative. Treated patients who become febrile should be assumed to have neutropenia until proven otherwise.
Cytopenia occurs in 5% to 25% of patients with rheumatoid arthritis (RA) who receive long-term therapy. Risk factors include renal dysfunction, preexisting folate deficiency, increased mean corpuscular volume value, advanced age, concomitant use of other anti-folate medications (such as trimethoprim-sulfamethoxazole), and possibly hypoalbuminemia, concomitant infection, history of bone marrow injury, surgery, and concurrent use of NSAIDs or probenecid. Pancytopenia is rarely observed in patients with rheumatoid arthritis. Bone marrow recovery typically occurs within two weeks after the withdrawal of MTX.
Gastrointestinal
Gastrointestinal side effects are usually controlled by folate supplementation (1 to 5 mg orally, given 4 hours before MTX or 1 mg orally once a day if on low dose therapy, as in rheumatoid arthritis), dosage reduction, dividing the dose over a 12 to 24 hour period, withholding the drug, or giving it parenterally.
Extremely rare cases of colitis and