Dihydrofolate Reductase Inhibitors

Dihydrofolate reductase inhibitors block the conversion of folic acid to tetrahydrofolic acid by inhibiting the dihydrofolate reductase enzyme.  High doses of folic acid or administration of leucovorin can be used to bypass dihydrofolate reductase inhibition. Administration of leucovorin is termed, "leucovorin rescue."  Drug-drug interaction, stomatitis, and myelosuppression are noted adverse effects.

Class Drugs

• Methotrexate

• Pemetrexed

• Pralatrexate

Class Mechanism of Action

Inhibits dihydrofolate reductase, which is an important enzyme for cell replication. 

Dihydrofolate reductase converts folic acid to its active form tetrahydrofolic acid

Inhibition of dihydrofolate reductase can be reversed with or administration of leucovorin, which bypasses the inhibited dihydrofolate reductase (AKA "leucovorin rescue")

Class Applications

See individual drugs

Class Adverse Effects

• Stomatitis/Mucositis

• Myelosuppression

• Drug-drug interactions

Drug Table

Drug Name	Application	Comments	Image
Methotrexate	Cancers; -Breast cancer; -Bladder cancer; -Head and neck cancer; -Acute lymphocytic leukemia; Inflammatory conditions; -Dosage lower than for chemotherapy.; -Decreases cytokine and inflammatory cell production; -Crohn's disease; -Rheumatoid Arthritis; -Psoriasis/Psoriatic arthritis		"Meth" "T-rex" "Ate"
Pemetrexed	Non small cell lung cancer		"Pen" "Mets" "T-rex"
Pralatrexate	T-cell lymphoma		"Prat" "Latrine" "T-Rex" "Ate"