Derm: alopecia, ERYTHEMA MULTIFORME, painful plaque erosions (during psoriasis treatment), photosensitivity, pruritus, rash, skin ulceration, soft tissue necrosis, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria.
EENT: blurred vision, transient blindness.
GI: anorexia, diarrhea, nausea, stomatitis, vomiting, GI PERFORATION, HEPATOTOXICITY.
GU: nephropathy, ↓ fertility, acute renal failure, menstrual abnormalities, oligospermia.
Hemat: anemia, leukopenia, thrombocytopenia, APLASTIC ANEMIA.
Metab: hyperuricemia.
MS: hemiparesis, osteonecrosis, stress fracture.
Neuro: arachnoiditis (IT use only), confusion, dizziness, drowsiness, dysarthria, headache, leukoencephalopathy, malaise, SEIZURES.
Resp: INTERSTITIAL PNEUMONITIS.
Misc: chills, fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION, SECONDARY MALIGNANCY, tumor lysis syndrome.
Acute Lymphoblastic Leukemia
- IV (Adults and Children): 10–5,000 mg/m2 followed by leucovorin rescue (for doses >500 mg/m2). Lower doses (20–30 mg/m2/wk may be used IM.
- PO (Adults): 20 mg/m2 once weekly.
Meningeal Leukemia
- IT (Adults and Children
9 yr): 12–15 mg given at intervals of 2 or more days up to twice weekly (for treatment) and no more than once weekly (for prophylaxis). - IT (Children 3–<9 yr): 12 mg given at intervals of 2 or more days up to twice weekly (for treatment) and no more than once weekly (for prophylaxis).
- IT (Children 2–<3 yr): 10 mg given at intervals of 2 or more days up to twice weekly (for treatment) and no more than once weekly (for prophylaxis).
- IT (Children 1–<2 yr): 8 mg given at intervals of 2 or more days up to twice weekly (for treatment) and no more than once weekly (for prophylaxis).
- IT (Children <1 yr): 6 mg given at intervals of 2 or more days up to twice weekly (for treatment) and no more than once weekly (for prophylaxis).
Non-Hodgkin's Lymphoma
- IV (Adults and Children): In combination with other chemotherapy agents: 1000 mg/m2 or 3000 mg/m2 over 24 hours followed by leucovorin rescue. CNS-directed therapy: 8000 mg/m2 over 4 hr followed by leucovorin rescue (as monotherapy) or 3000–8000 mg/m2 followed by leucovorin rescue (in combination with immunochemotherapy).
- PO (Adults): 2.5 mg 2–4 times weekly.
Osteosarcoma
- IV (Adults and Children): 12 g/m2 (max = 20 g/dose) over 4 hr followed by leucovorin rescue, usually as part of a combination chemotherapeutic regimen (or ↑ dose until peak serum methotrexate level is 1 × 10-3 M/L but not to exceed 15 g/m2); 12 courses are given starting 4 wk after surgery and repeated at scheduled intervals.
Breast Cancer
- IV (Adults): 40 mg/m2 on days 1 and 8 (with other agents; many regimens are used).
Squamous Cell Carcinoma of Head and Neck
- IV (Adults): 40–60 mg/m2 once weekly.
Gestational Trophoblastic Neoplasia
- IV, IM (Adults): Low-risk gestational trophoblastic neoplasia: 30–200 mg/m2.
- IV (Adults): High-risk gestational trophoblastic neoplasia: 300 mg/m2 over 12 hr (with other agents).
Mycosis Fungoides
- PO (Adults): Monotherapy: 25–75 mg once weekly; As part of combination regimen: 10 mg/m2 twice weekly.
- IM (Adults): Early stage: 5–50 mg once weekly; If poor response to weekly therapy: 15–37.5 mg twice weekly.
Rheumatoid Arthritis
- PO, IM, SC (Adults): 7.5 mg once weekly (not to exceed 20 mg/wk); when optimal clinical response is obtained, dose should be ↓. Otrexup may be used when dose is 10–20 mg/wk.
Polyarticular Juvenile Idiopathic Arthritis
- PO, IM, SC (Children): 10 mg/m2 once weekly initially, may be ↑ up to 20–30 mg/m2; however, response may be better if doses >20 mg/m2 are given IM or SUBQ; Otrexup may be used when dose is 10–25 mg/wk.
Psoriasis
Therapy may be preceded by a 5–10-mg test dose
- PO, IM, SC, IV (Adults): 10–25 mg once weekly (not to exceed 25 mg/wk); when optimal clinical response is obtained, dose should be ↓. Otrexup may be used when dose is 10–25 mg/wk.
Jylamvo, Otrexup, Rasuvo, Rheumatrex, Trexall, Xatmep
Therapeutic Classification: antineoplastics, antirheumatics (DMARDs), Immunosuppressant agents
Pharmacologic Classification: antimetabolites
Absorption: Small doses are well absorbed from the GI tract. Larger doses incompletely absorbed.
Distribution: Actively transported across cell membranes, widely distributed. Does not reach therapeutic concentrations in the CSF. Absorption in children is variable (23–95%) and dose-dependent.
Metabolism/Excretion: Excreted mostly unchanged by the kidneys.
Half-life: Low dose: 3–10 hr; high dose: 8–15 hr (↑ in renal impairment).
(effects on blood counts)