PARTNERS WITH
Methotrexate
Anti-metabolite
MECHANISM OF ACTION
Inhibit DNA synthesis (dihydrofolate inhibitor)
MECHANISM OF KIDNEY INJURY
Crystallization of MTX in the kidney tubular lumen. Other possible mechanisms; vasoconstriction of afferent capillary and direct effects on renal tubular cells
CLINICAL KIDNEY SYNDROME
CARDIOVASCULAR ADVERSE EFFECTS
Several clinical trials have shown that MTX is associated with improved endothelial function, slower atherosclerosis progression, and decreased risk of major cardiovascular adverse events.
LYTE ABNORMALITIES
Mucositis, Myelosuppresion, megaloblastic anemia, ILD, renal failure, hepatotoxic, neurotoxic
RISK FACTORS
MITIGATION STRATEGIES
High Dose MTX: IV hydration UOP >2.5L/day. IV alkalization of urine to pH >7.0 (serum <8.0 and bicarb 35). Continue MTX <0.1. MTX toxicity extracorporal removal not recommended. Glucarpidase recommended (EXTRIP)
SUGGESTIONS
NOTES/COMMENTS
eGFR, 30-59 ml/min, 50-60% of normal dose
eGFR < 30 ml/min, avoid use
PHARMACOKINETICS
Molecular Weight
454
Volume of Distribution
Plasma Protein Binding
50%
Metabolism
hepatic and intestinal
Bioavailability
Half-life elimination
High Dose 8-15hr; Low Dose 3-10
Time to peak
Excretion
Renal, 44%-100%
Dialyzable?
avoid use or consider 75% dose reduction
REF:
PATHOLOGY SLIDES:
ENTRY UPDATES:
Raad Chowdhury
United States
Sep 25, 2022