Methotrexate | | Figure 7.2 Metabolic pathway inhibited by methotrexate |
(Figure 7.2) - Antimetabolite and antifolate drug; inhibits dihydrofolate reductase (DHFR) involved in folic acid pathway, which is necessary for DNA/RNA synthesis (via purine and thymidylate synthesis); S phase specific
- Renal excretion; liver biopsy at cumulative dose of 1.5 g; treat acute toxicity with leucovorin; caution in patients with ↑ alcohol intake, diabetes, or renal failure
- SE: hepatotoxicity, pancytopenia, teratogenicity, radiation recall, acral erythema, teratogenicity (egg and sperm), ± lymphoma
- ↑ Pancytopenia risk with concomitant use of: NSAID, dapsone, TMP/SMX, or no folate supplementation; ↑ MTX levels with concomitant use of TCN, phenytoin, phenothiazine, barbiturate, NSAID, salicylate, sulfonamide
- Pregnancy category C
|
