Methotrexate

DEA Class; Rx

Common Brand Names; Trexall, Otrexup, Rasuvo, Xatmep, RediTrex, Jylamvo

Folate antimetabolite
Used for malignant (e.g., breast cancer, non-Hodgkin lymphoma, ALL) and nonmalignant diseases (e.g., rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis); intrathecal methotrexate used for prophylaxis and treatment of meningeal leukemia
Use is contraindicated in patients with a nonmalignant diagnosis who are pregnant; due to the potential for serious or fatal adverse reactions, treatment with methotrexate requires an experienced physician

Pregnant women with nonmalignant disease

Known hypersensitivity; severe reactions observed

• Arachnoiditis with intrathecal administration
• Subacute toxicity with intrathecal administration (paralysis of extremities, cranial nerve palsy, seizure or coma)
• Demyelinating encephalopathy with cranial irradiation or other systemic chemotherapy
• Reddening of skin
• Hyperuricemia
• Ulcerative stomatitis
• Glossitis
• Gingivitis
• Nausea and vomiting
• Diarrhea
• Anorexia
• Intestinal perforation
• Mucositis (dose-dependent)
• Leukopenia
• Thrombocytopenia
• Renal failure
• Azotemia
• Nephropathy
• Pharyngitis

Based on published reports and its mechanism of action, can cause embryofetal toxicity, including fetal death; contraindicated in females with nonmalignant disease

Hypersensitivity reactions, including anaphylaxis, reported; if hypersensitivity occurs, immediately discontinue and institute appropriate therapy

Myelosuppression reported, including severe and life-threatening pancytopenia, anemia, aplastic anemia, leukopenia, neutropenia, and thrombocytopenia; obtain blood counts at baseline and periodically; provide supportive care and withhold, reduce dose, or discontinue methotrexate if needed

GI toxicity may occur, including diarrhea, vomiting, stomatitis, hemorrhagic enteritis, and fatal intestinal perforation; patients with peptic ulcer disease or ulcerative colitis at greater risk; withhold or discontinued for severe GI toxicity and institute supportive care

Pulmonary toxicity reported, including acute or chronic interstitial pneumonitis and irreversible or fatal cases can occur at all dose levels; pulmonary symptoms (especially a dry, non-productive cough) may require interruption of therapy and careful investigation

Pulmonary toxicity reported, including acute or chronic interstitial pneumonitis and irreversible or fatal cases can occur at all dose levels

Secondary malignancies can occur at all dose levels; in some cases, lymphoproliferative disease that occurred during therapy with low-dose methotrexate regressed completely following withdrawal of methotrexate; if lymphoproliferative disease occurs, discontinue and institute appropriate treatment if lymphoma does not regress

Can induce tumor lysis syndrome with rapidly growing tumors; institute appropriate treatment for prevention and management

Can cause impairment of fertility, oligospermia, and menstrual dysfunction; unknown if infertility is reversible; discuss reproduction risks with female and male patients of reproductive potential

Based on published reports and mechanism of action, can cause embryo-fetal toxicity and fetal death when administered to pregnant women

Limited published literature report the presence of methotrexate in human milk in low amounts; no information is available on the effects on breastfed infants or milk production

NOTE: The suggested maximum tolerated dose (MTD) for methotrexate is dependent on the disease state, performance status, and other chemotherapy agents or radiation given in combination.
NOTE: The correct dose of methotrexate in the treatment of neoplastic disease will vary from protocol to protocol. Clinicians should consult the appropriate references to verify the dose.