Choriocarcinoma and other trophoblastic diseases: 15–30 mg PO or IM daily for a 5-day course. Repeat courses three to five times with rest periods of 1 wk or longer between courses until toxic symptoms subside. Continue one to two courses of methotrexate after chorionic gonadotropin hormone levels are normal.

Leukemia: Induction: 3.3 mg/m² of methotrexate PO or IM with 60 mg/m² of prednisone daily for 4–6 wk. Maintenance: 30 mg/m² methotrexate PO or IM twice weekly or 2.5 mg/kg IV every 14 days. If relapse occurs, return to induction doses.

Meningeal leukemia: Give methotrexate intrathecally in cases of lymphocytic leukemia as prophylaxis. 12 mg/m² (maximum 15 mg) intrathecally at intervals of 2–5 days; repeat until cell count of CSF is normal, then give one additional dose.

Lymphomas: Burkitt tumor, stages I and II: 10–25 mg/day PO for 4–8 days. In stage III, combine with other neoplastic drugs. All usually require several courses of therapy with 7- to 10-day rest periods between doses.

Mycosis fungoides: 2.5–10 mg/day PO for weeks or months or 50 mg IM once weekly or 25 mg IM twice weekly. Alternatively, in early stage, 5–50 mg PO or IM once weekly, or 15–37.5 mg PO or IM twice weekly; can also give IV with combination chemotherapy regimens in advanced disease.

Osteosarcoma: Starting dose is 12 g/m² or up to 15 g/m² IV to give a peak serum concentration of 1,000 micromol. Must be used as part of a cytotoxic regimen with leucovorin rescue.

Severe psoriasis: 10–25 mg/wk PO, IM, or IV as a single weekly dose. Do not exceed 30 mg/wk. Or 2.5 mg PO at 12-hr intervals for three doses each wk. Do not exceed 30 mg/wk. After optimal clinical response is achieved, reduce dosage to lowest possible with longest rest periods and consider return to conventional, topical therapy.

Severe rheumatoid arthritis: Starting dose: Single doses of 7.5 mg/wk PO or divided dosage of 2.5 mg PO at 12-hr intervals for three doses given as a course once weekly. Dosage may be gradually increased, based on response. Do not exceed 20 mg/wk. Therapeutic response usually begins within 3–6 wk, and improvement may continue for another 12 wk. Improvement may be maintained for up to 2 yr with continued therapy.

Younger than 1 yr: 6 mg intrathecally every 2–5 days.

1–2 yr: 8 mg intrathecally every 2–5 days.

2–3 yr: 10 mg intrathecally every 2–5 days.

3 yr or older: 12 mg intrathecally every 2–5 days.

Polyarticular course juvenile rheumatoid arthritis (2–16 yr): Initially, 10 mg/m² PO weekly. Dosage may be increased based on patient response. Maximum 20 mg/m²/wk. Therapeutic response usually begins in 3–6 wk.