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leucovorin
generic
Adult Dosing .
Dosage forms: TAB: 5 mg, 10 mg, 15 mg, 25 mg; INJ: 10 mg per mL, 20 mg per mL
colorectal CA
- [combo w/ fluorouracil 370 mg/m^2/day]
- Dose: 200 mg/m^2/dose IV x1 on days 1-5 of 28-day cycle; Info: give x2 cycles, then cont. 28-day cycles or extend to 35-day cycles; dosing protocols may vary; see pkg insert for 5-FU dose adjustments based on toxicity
- [combo w/ fluorouracil 425 mg/m^2/day]
- Dose: 20 mg/m^2/dose IV x1 on days 1-5 of 28-day cycle; Info: give x2 cycles, then cont. 28-day cycles or extend to 35-day cycles; dosing protocols may vary; see pkg insert for 5-FU dose adjustments based on toxicity
leucovorin rescue, high-dose methotrexate
- [normal methotrexate elimination]
- Dose: 15 mg PO/IM/IV q6h x10 doses; Start: 24h after methotrexate start; Max: 25 mg/dose PO, may give higher doses IM/IV; Info: cont. until methotrexate level <0.05 micromolar; use this regimen if methotrexate level approx. 10 micromolar at 24h, 1 micromolar at 48h, and <0.2 micromolar at 72h after methotrexate start; may incr. to 14 doses w/ subsequent cycles if abnormal methotrexate elimination but not severe enough to require adjustments below
- [delayed late methotrexate elimination]
- Dose: 15 mg PO/IM/IV q6h; Max: 25 mg/dose PO, may give higher doses IM/IV; Info: cont. until methotrexate level <0.05 micromolar; use this regimen if methotrexate level >0.2 micromolar at 72h and >0.05 micromolar at 96h after methotrexate start
- [delayed early methotrexate elimination and/or acute renal injury]
- Dose: 150 mg IV q3h until methotrexate level <1 micromolar, then 15 mg IV q3h; Info: cont. until methotrexate level <0.05 micromolar; use this regimen if methotrexate level >50 micromolar at 24h or >5 micromolar at 48h OR if SCr incr. 100% from baseline at 24h after methotrexate start; use in combo w/ hydration and urinary alkalinization
leucovorin rescue, methotrexate overdose
- [10 mg/m^2/dose PO/IM/IV q6h]
- Start: ASAP after overdose and w/in 24h if delayed methotrexate elimination; Max: 25 mg/dose PO, may give higher doses IM/IV; Info: cont. until methotrexate level <0.01 micromolar; incr. dose to 100 mg/m^2/dose IV q3h if SCr incr. 50% from baseline at 24h OR if methotrexate level >5 micromolar at 24h or >0.9 micromolar at 48h
folate antagonist overdose
- [pemetrexed]
- Dose: 50 mg/m^2/dose IV q6h x8 days; Start: 100 mg/m^2/dose IV x1
- [pyrimethamine, trimethoprim]
- Dose: 5-15 mg PO/IM/IV qd until hematopoiesis restored
megaloblastic anemia, folate deficiency-associated
- [<1 mg IM/IV qd]
- Max: 1 mg/day
folate deficiency prevention, pyrimethamine-induced (off-label)
- [PCP or toxoplasmosis prophylaxis use]
- Dose: 25 mg PO qwk
- [toxoplasmosis treatment or maintenance use]
- Dose: 10-25 mg PO qd
- [cystoisosporiasis treatment or maintenance use]
- Dose: 5-25 mg PO qd
renal dosing
- [not defined]
- renal impairment: not defined
- HD/PD: not defined
hepatic dosing
- [not defined]
Peds Dosing .
- Dosage forms: TAB: 5 mg, 10 mg, 15 mg, 25 mg; INJ: 10 mg per mL, 20 mg per mL
leucovorin rescue, high-dose methotrexate
- [normal methotrexate elimination]
- Dose: 10 mg/m^2/dose PO/IM/IV q6h x10 doses; Start: 24h after methotrexate start; Max: 25 mg/dose PO, may give higher doses IM/IV; Info: cont. until methotrexate level <0.05 micromolar; use this regimen if methotrexate level approx. 10 micromolar at 24h, 1 micromolar at 48h, and <0.2 micromolar at 72h after methotrexate start; may incr. to 14 doses w/ subsequent cycles if abnormal methotrexate elimination but not severe enough to require adjustments below
- [delayed late methotrexate elimination]
- Dose: 10 mg/m^2/dose PO/IM/IV q6h; Max: 25 mg/dose PO, may give higher doses IM/IV; Info: cont. until methotrexate level <0.05 micromolar; use this regimen if methotrexate level >0.2 micromolar at 72h and >0.05 micromolar at 96h after methotrexate start
- [delayed early methotrexate elimination and/or acute renal injury]
- Dose: 100 mg/m^2/dose IV q3h until methotrexate level <1 micromolar, then 10 mg/m^2/dose IV q3h; Info: cont. until methotrexate level <0.05 micromolar; use this regimen if methotrexate level >50 micromolar at 24h or >5 micromolar at 48h OR if SCr incr. 100% from baseline at 24h after methotrexate start; use in combo w/ hydration and urinary alkalinization
leucovorin rescue, methotrexate overdose
- [10 mg/m^2/dose PO/IM/IV q6h]
- Start: ASAP after overdose and w/in 24h if delayed methotrexate elimination; Max: 25 mg/dose PO, may give higher doses IM/IV; Info: cont. until methotrexate level <0.01 micromolar; incr. dose to 100 mg/m^2/dose IV q3h if SCr incr. 50% from baseline at 24h OR if methotrexate level >5 micromolar at 24h or >0.9 micromolar at 48h
folate antagonist overdose
- [pyrimethamine, trimethoprim]
- Dose: 5-15 mg PO/IM/IV qd until hematopoiesis restored
megaloblastic anemia, folate deficiency-associated
- [<1 mg IM/IV qd]
- Max: 1 mg/day
folate deficiency prevention, pyrimethamine-induced (off-label)
- [toxoplasmosis prophylaxis or suppression use]
- Dose: 5 mg PO q3 days
- [congenital toxoplasmosis treatment use]
- Dose: 10 mg PO/IM w/ each pyrimethamine dose
- [acquired toxoplasmosis treatment use]
- Dose: 10-25 mg PO qd
- [cystoisosporiasis use]
- Dose: 5-15 mg PO qd
renal dosing
- [not defined]
- renal impairment: not defined
- HD/PD: not defined
hepatic dosing
- [not defined]
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- intrathecal use
- GI toxicity, unresolved (colorectal CA use)
- caution: anemia, pernicious
- caution: megaloblastic anemia, vitamin B12-deficiency
- caution: vitamin B-12 deficiency
Drug Interactions .
Overview
leucovorin
folate analog
- glucarpidase substrate
- levoleucovorin is the active isomer of racemic leucovorin; similar interactions anticipated
Avoid/Use Alternative
- capecitabine
- pafolacianine
- sulfamethoxazole
- trimethoprim
Monitor/Modify Tx
- fosphenytoin
- glucarpidase
- pentobarbital
- phenobarbital
- phenytoin
- primidone
Caution Advised
- fluorouracil
Adverse Reactions .
Serious Reactions
- anaphylactoid rxn
- GI toxicity (colorectal CA use)
- seizures
- syncope
- hypercalcemia (IV use)
Common Reactions
- urticaria
- vomiting (IV use)
- nausea (IV use)
Safety/Monitoring .
Monitoring Parameters
Adv. Colorectal CA Fluorouracil Adjuvant Tx: CBC w/ diff before every cycle, then qwk during 1st 2 cycles, then once per cycle during anticipated WBC nadir; electrolytes, LFTs before each cycle x3, then before every other cycle
Other Indications: no routine tests recommended
Benzyl Alcohol Content
if dose >10 mg/m^2 use sterile water for injection as diluent to avoid benzyl alcohol toxicity
Look/Sound-Alike Drug Names
leucovorin confused with: Leukeran; LEVOleucovorin; Leukine; levothyroxine
Pregnancy/Lactation .
Pregnancy
Clinical Summary
may use during pregnancy; no known risk of fetal harm based on human data
Lactation
Clinical Summary
may use while breastfeeding; no human data available, though risk of infant harm not expected based on drug properties; no human data available to assess effects on milk production
Pharmacology .
Metabolism: liver, GI tract; CYP450: unknown; Info: active metabolite
Excretion: urine 80-90%, fecal 5-8%; Half-life: 6.2h
Subclass: Folate Derivatives, Oncologic ; Supportive Care: Folate Analog Toxicity ; Toxicity: Drugs
Mechanism of Action
participates in reactions utilizing folates, counteracting folate antagonists (folic acid analog)
Formulary .
No Formulary Selected
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