Dosing and uses of Leucovorin
Adult dosage forms and strengths
tablets
- 5mg
- 10mg
- 15mg
- 25mg
powder for injection
- 50mg
- 100mg
- 200mg
- 350mg
- 500mg
injectable solution
- 10mg/mL
Methotrexate Overdose
1:1 ratio for leucovorin to inadvertent methotrexate overdose, within 1 hr
Initial IV, then may switch to IM q6hr and continue until methotrexate level has fallen below 0.05 micromolar and the renal failure has resolved
High Dose Methotrexate Rescue
10 mg/m² IV q6hr starting 24 hr after methotrexate
May give PO after 1st IV dose
Coadministration with Trimetrexate (Discontinued)
20 mg/m² IV/PO q6hr (for PO, round dose up to next 25 mg increment)
Dose adjustment for both trimetrexate & leucovorin may be necessary if hematologic toxicity occurs
Advanced Colorectal Carcinoma (with 5FU)
Recommended 20 mg/m² IV followed by 425 mg/m² fluorouraciL
Dose reduction treatment pause may be necessary based on hematologic toxicity
Methanol Poisoning
1 mg/kg (50-70 mg adults) IV q4-6hr
Trimethoprim Toxicity
10 mg/m² PO q6hr
Other Indications & Uses
Bone marrow suppression due to folic acid antagonism, megaloblastic anemia
Pediatric dosage forms and strengths
tablets
- 5mg
- 10mg
- 15mg
- 25mg
powder for injection
- 50mg
- 100mg
- 200mg
- 350mg
- 500mg
injectable solution
- 10mg/mL
Methotrexate Overdose
1:1 ratio for leucovorin to inadvertent methotrexate overdose, within 1 hr
Initial IV, then may switch to IM q6hr and continue until methotrexate level has fallen below 0.05 micromolar and the renal failure has resolved
High Dose Methotrexate Rescue
10 mg/m² IV q6hr starting 24 hr after methotrexate
May give PO after 1st IV dose
Trimethoprim Toxicity
10 mg/m² PO q6hr
Leucovorin adverse (side) effects
Frequency not defined
Diarrhea
Nausea
Vomiting
Stomatitis
Thrombocytosis
Anaphylactoid reaction
Wheezing
Urticaria
Anaphylactoid reactions
Warnings
Contraindications
Vitamin B12 deficiency anemia and pernicious anemia
Cautions
Hypersensitivity reactions including anaphylactoid reactions & urticaria
Risk of severe neurological complications in patients with undiagnosed anemia
Geriatric or debilitated patients receiving cotreatment with fluorouraciL
May increase tosicity of 5-fluorouraciL
May increase treatment failure of sulfamethoxazole-trimethoprim therapies
Formulations containing benzyl alcohol not to be used in infants
Thrombocytosis reported during intra-arterial infusion of methotrexate
Pregnancy and lactation
Pregnancy category: C
Lactation: not known whether distributed in breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Leucovorin
Mechanism of action
Serves as a cofactor supplement to counteract folic acid antagonists such as methotrexate; leucovorin is an active metabolite of folic acid
Displaces methotrexate from intracellular binding sites and restores the folate required for DNA/RNA synthesis
In methanol toxicity it serves as a tetrahydrofolate source to help the body eliminate the formic acid resulting from methanol's toxicity
Pharmacokinetics
Distribution: all body tissues, predominantly in liver
Metabolism: Rapidly converted to THF derivatives
Excretion: Urine (primarily); feces
Half-life elimination: 4-8hr
Peak plasma time: 2 hr (PO); 10 min (as folate); 1 hr (as tetrahydrofolate)
Administration
IV Incompatibilities
Additive: fluorouracil, trimetrexate
Syringe: droperidol, trimetrexate, fluorouraciL
Y-site: amphotericin B cholesteryl sulfate, droperidol, foscarnet, NaHCO3
IV Compatibilities
Solution: compatible w/ most common fluids
Additive: cisplatin, cisplatin w/ floxuridine, floxuridine
Syringe: bleomycin, cisplatin, cyclophosphamide, doxorubicin, droperidol, fluorouracil, furosemide, heparin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine
Y-site (partial list): bleomycin, cisplatin, cyclophosphamide, fluorouracil(?), furosemide, heparin, linezolid, methotrexate, metoclopramide, mitomycin
IV Preparation
Reconstitute w/ BWI or SWI of 10 mg/mL or 20 mg/mL (for 350 mg vial)
Available in 10 mg/mL preservative-free solutions
Do not use benzyl alcohol-containing diluents for doses >10 mg/sq.meter
Reconstituted solution is stable for 7 d
Use immediately if reconstituted w/ preservative-free solution
IV/IM Administration
Infusion: not to exceed 160 mg/min
