THERAPEUTICS

Brands

• Amethopterin, Emthexate, Ledertrexate, Maxtrex, Mexate, MTX, Otrexup, Trexall, Rheumatrex, Metoject

Generic?

• Yes

Class

• Antineoplastic agent, immunosuppressant

Commonly Prescribed for

(FDA approved in bold)

• Treatment of malignancies, including non-Hodgkin lymphoma, gestational choriocarcinoma, head and neck epidermoid cancer, and lung and breast cancer

• Psoriasis

• Rheumatoid arthritis

• Inflammatory myopathies: polymyositis (PM) and dermatomyositis (DM)

• Vasculitis, including Wegener’s granulomatosis

• Relapsing-remitting or chronic progressive multiple sclerosis (MS)

• Primary CNS lymphoma

• Ulcerative colitis or Crohn's disease

• Systemic lupus erythematosus

• Psoriatic arthritis

How the Drug Works

• Inhibits dihydrofolic acid reductase. Prevents synthesis of purine nucleotides and thymidylate. This interferes with DNA synthesis, repair, and replication

How Long Until It Works

• Within a week, but effect on neurological diseases may take months

If It Works

• DM/PM: improves strength, and may allow discontinuation or reduced dose of corticosteroids. Corticosteroids are tapered first. Taper slowly over 6 months if clinical remission occurs

• MS: may reduce relapses and new lesions on MRI

• Other disorders: Improves symptoms and clinical markers of the disease

If It Doesn't Work

• DM/PM: question the diagnosis (inclusion-body myositis, hypothyroidism, muscular dystrophy), rule out corticosteroid-induced myopathy, and evaluate for undiagnosed malignancy (especially in DM). Change to azathioprine

• MS: if clearly not helpful, change to another agent

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Usually used in combination with corticosteroids (to reduce corticosteroid dose) in DM and PM. Occasionally combined with other treatments for the treatment of MS

Tests

• Obtain CBC, liver and renal function tests, and chest x-ray at baseline and at dosage adjustments, or for any clinical symptoms. Use serum level and WBC to assess response to treatment

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Folic acid antagonism

Notable AEs

• Ulcerative stomatitis, nausea, abdominal distress

• Malaise, fatigue, chills and fever, dizziness

• Headache, speech impairment, convusions, encephalopathy

• Rash or photosensitivity

• Elevated liver function tests (up to 15%)