Dosage Forms. Tablet: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg
Common FDA Label Indication, Dosing, and Titration.
1. Non-Hodgkin lymphoma, advanced (Burkitt lymphoma, stages I and II): 10-25 mg/d po for 4-8 d for several courses with a 7-10 d rest period
2. Psoriasis (Severe): 10-25 mg/wk po or 2.5 mg q12h × 3 doses
3. Rheumatoid arthritis, severe: 10-15 mg po once weekly, may titrate by 5 mg/wk every 2-3 wk to max 20-30 mg/wk
4. Juvenile rheumatoid arthritis, polyarticular course: 10 mg/m2 po once weekly, may titrate to clinical response
1. Many cancers: Dose varies with cancer, stage, and concurrent chemotherapy
MOA. Reversibly inhibits dihydrofolate reductase (DHFR). Dihydrofolates are reduced to tetrahydrofolates by DHFR before they are used in DNA synthesis. Methotrexate interferes with DNA synthesis, repair, and cellular replication.
Drug Characteristics: Methotrexate
Medication Safety Issues: Methotrexate
Drug Interactions: Methotrexate
Adverse Reactions: Methotrexate
Efficacy Monitoring Parameters. Resolution of symptoms of psoriasis. Decreased pain and improved range of motion in rheumatoid arthritis. Shrinkage or disappearance of tumor. Methotrexate levels may be monitored and used to adjust leucovorin.
Toxicity Monitoring Parameters. Baseline and periodic CBC, SCr, LFTs, negative pregnancy test. Seek medical attention if severe mouth ulcerations, fever >101.5°F, shortness of breath, changes in urination, yellowing of eyes or skin, unusual bruising, or bleeding.
Key Patient Counseling Points. Causes nausea and vomiting; make sure you have antiemetics and know how to take them. Avoid sun exposure. May take with food.
Clinical Pearls. High dose methotrexate requires urine alkalinization with sodium bicarbonate infusions to enhance methotrexate excretion and requires leucovorin administration started 24 h after methotrexate to rescue normal cells. Elimination is reduced in patients with ascites and/or pleural effusions related to third spacing, resulting in prolonged half-life and toxicity. Concomitant methotrexate administration with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis. Numerous dosing regimens are used; do not confuse daily and weekly dosing strategies.