MSK: MTX

Question 1

MTX: INDICATIONS

Answer 1

• DMARD for RA
• Severe Psoriasis and Psoriatic Arthritis (which is resistant to other Tx)
• Chemo regimens for Cancer (Leukemia, Lymphoma, some solid tumors)

Question 2

MTX: MOA

Answer 2

• Inhibits Dihydrofolate Reductase - Converts dietary Folic Acid to FH4
• FH4 required for DNA and protein synthesis, lack of FH4 prevents CELLULAR REPLICATION
• Anti-inflammatory + immunosuppressive effects
• Inhibition of IL6, 8 and TNF ALPHA

Question 3

MTX: ADVERSE EFFECTS

Answer 3

• Mucosal damage (sore mouth, GI upset)
• Bone Marrow Suppression (Neutropenia and increased risk of infection)
• RARELY, Hypersensitivity Rxns (Cutaneous Rxns, hepatitis, pneumonitis)
• LT Use = Hepatic Cirrhosis and Pulmonary Fibrosis
• Risk of accidental OD if taken daily

Question 4

MTX: WARNINGS

Answer 4

• Teratogenic = avoided in pregnancy (men and women taking the drug should use effective contraception during and for 3 months after stopping tx)
• CI in Severe renal impairment
• Abnormal liver fxn (causes hepatotoxicity)

Question 5

MTX: INTERACTIONS

Answer 5

MTX toxicity is more likely if it is prescribed with drugs that inhibit its renal excretion
- NSAIDs, Penicillins

Co-prescription with other folate antagonists increases risk of haematological malignancies
- Trimethoprim, Phenytoin

Risk of Neutropenia is increased if MTX is combined with CLOZAPINE