Class: Reduced folate (vitamin B9) analog
Mechanism of Action
- Bypasses dihydrofolate reductase (DHFR) → replenishes reduced folate pools
- Enhances or counteracts the effects of antifolate drugs depending on context:
- Rescue after high-dose methotrexate → protects normal cells
- Enhances 5-FU activity by stabilizing the 5-FU–thymidylate synthase complex
Indications
- Methotrexate rescue (high-dose MTX regimens in ALL, osteosarcoma, lymphoma)
- Enhancer of 5-FU cytotoxicity (e.g., colorectal cancer regimens)
- Antidote for folate antagonist toxicity (e.g., accidental methotrexate overdose, trimethoprim toxicity)
Dosing
- MTX rescue:
- Typically begins 24 hours after methotrexate infusion
- Dose and duration guided by MTX levels (e.g., 10–15 mg/m² every 6 hours, or higher)
- 5-FU enhancement:
- 200–400 mg/m² IV bolus before or with 5-FU
- Available as IV, IM, or oral (IV preferred for high-dose rescue)
Key Adverse Effects
- Generally well tolerated
- Rare: allergic reactions, rash, GI upset
- Can mask vitamin B12 deficiency (with long-term use)
Monitoring
- Serum methotrexate levels and renal function (in high-dose MTX regimens)
- CBC and electrolytes if used with chemotherapy
- Assess for timely initiation (delays can worsen toxicity)
Drug Interactions
- Avoid concurrent use with oral calcium folinate and methotrexate (interferes with MTX effect)
- Enhances efficacy and toxicity of 5-FU
Other Notes
- Not interchangeable with folic acid or levoleucovorin (isomer-specific dosing may differ)
- Oral absorption saturates at higher doses → IV preferred for MTX rescue
- Must be continued until MTX levels fall below safe threshold (<0.05–0.1 μM depending on protocol)