Folate Antimetabolites

Question 1

MOA folate antimetabolites

Answer 1

INTERFERE with the enzymes involved in the FOLIC ACID CYCLE, blocking purine and pyrimidine biosynthesis during the S PHASE

Question 2

list folate antimetabolite drugs

Answer 2

Methotrexate (MTX)

pemetrexed
pralatrexate

Question 3

safety concerns for MTX

Answer 3

1. Nephrotoxicity (with high doses ≥ 500 mg/m2)
2. Gastrointestinal toxicity (DIARRHEA, MUCOSITIS)

Question 4

Prevention strategies of nephrotoxicity of MTX

Answer 4

1. LEUCOVORIN or LEVOCOVORIN “rescue”
2. HYDRATION with IV SODIUM BICARBONATE to ALKALINIZE the URINE (improves MTX solubility)
3. Avoid interacting medications (NSAIDS, SALICYLATES, B-lactams, PPI, sulfa abx, probenacid)
4. Caution in pts w/ 3rd spacing (ascites, pleural effusions) which delay drug clearance

Question 5

Tx strategies (ANTIDOTE used) for MTX nephrotoxicity

Answer 5

Antidote: Glucarpidase (Voraxaze) rapidly LOWERS MTX LEVELS in pts with MTX induced AKI and delayed MTX clearance

Question 6

Tx strategies (ANTIDOTE used) for MTX nephrotoxicity

Answer 6

Antidote: Glucarpidase (Voraxaze) rapidly LOWERS MTX LEVELS in pts with MTX induced AKI and delayed MTX clearance

Question 7

What is the “rescue” drug for gastrointestinal toxicity for high dose MTX

Answer 7

Leucovorin or Levoleucovorin

Question 8

what is the prevention/ treatment strategies for GI toxicity (diarrhea and mucositis)

Answer 8

Same as pyrimidine antimetabolites

Question 9

what other conditions can be caused by prolonged use of MTX for chronic conditions (rheumatoid arthritis, psoriasis)

Answer 9

Hepatotoxicity and Photosensitivity