Leucovorin
WELLCOVORIN
What it isReduced folate bypassing dihydrofolate reductase; methotrexate rescue and fluorouracil potentiation.
Why this oneIt rescues normal cells from methotrexate yet paradoxically strengthens fluorouracil's antitumor effect.
What limits it⚑ Rescue must start on time; delay makes it ineffective. It does not correct renal methotrexate retention.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Reduce methotrexate toxicity (impaired MTX elimination) | Adults | 10 mg/m² (up to 25 mg) q6h | 10 mg/m² (up to 25 mg) q6h until MTX <0.01 µM | 25 mg q6h (above this, use parenteral) |
| Folic acid antagonist / DHFR inhibitor overdose | Adults | 5–15 mg QD | 5–15 mg QD | 15 mg QD |
| FOLR1-CFTD (cerebral folate transport deficiency) | <40 kg | 1–2 mg/kg/day | up to 8.5 mg/kg/day | 8.5 mg/kg/day |
| FOLR1-CFTD | ≥40 kg | 1–2 mg/kg/day | up to 330 mg/day | 330 mg/day |
Renal Undefined
Hepatic Undefined
For MTX rescue, doses >25 mg q6h require switch to injectable leucovorin.
Instructions
- Oral only; with or without food.
- May crush and mix with food/liquid; give immediately after mixing.
- MTX rescue: give within 24 hr of MTX / ASAP after antagonist overdose; maintain IV fluids 3 L/day and alkalinize urine to pH ≥7.0.
- FOLR1-CFTD: total daily dose once daily or divided up to 6x/day; single doses ≤25 mg preferred, do not exceed 75 mg as a single dose.
Contraindications
- Hypersensitivity to leucovorin, levoleucovorin, or folic acid — severe reaction (antagonist/DHFR toxicity indication) or any reaction (FOLR1-CFTD); anaphylaxis reported
Cautions
- Hypersensitivity/anaphylactic reactions — withhold or discontinue based on severity
Adverse reactions
- Pruritus, rash, urticaria
- Dyspnea
- Rigors, temperature change
Pregnancy No drug-associated risk identified for intermittent use (antagonist/DHFR toxicity); concomitant chemotherapy may cause fetal harm.
Lactation No data on presence in human milk.
NO BOXED WARNINGS
Principal riskRescue must start on time or it is useless
Cost, est. cash$20–$1,500/dose or month
Generic entry1982
Classes and tags
Clinical profile
Legacy pregnancy categoryUnknown / historical label unavailable
Defining liabilityGenerally tolerated at therapeutic doses; clinically important risks are agent-specific and increase with interactions or organ impairment.
Mechanism of action: Leucovorin ballicule
