Parenteral Manual

Leucovorin calcium

Disclaimer: Official controlled document is the CHEO online copy. It is the responsibility of user to ensure that any paper copy version is the same as the online version before use.

Alternate Name(s): 
Folid Acid Derivative
Original Date: 
August 2005
Revised Date: 
December 2019
  • To counteract ("rescue") the continuing marrow toxicity of large doses of folic acid antagonists (especially methotrexate >300 mg/m2)
  • Treatment of megaloblastic anemia due to folate deficiency, when oral therapy is not feasible
Reconstitution and Stability: 
  • Available as a 10 mg/mL solution
  • Refrigerate vials. Stable 7 days at room temperature
  • Stable 24 hours at room temperature when diluted in compatible solutions
  • Stable 8 hours in syringe (Novopharm product)
  • Stable 48 hours at room temp and 7 days in fridge (Hospira product)
  • Protect from light

- Solutions Compatible: dextrose solutions up to D10W, 0.9% NaCl, and combinations

- Additive/Above Cassette Compatible: no information

- Y-site Compatible: filgrastim, fluconazole, 5-fluorouracil, heparin, metoclopramide, non-acetate containing TPN (amino acids/dextrose)

- Incompatible: amphotericin B, sodium bicarbonate, droperidol


(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)

IV Direct NO
IV Intermittent Infusion

Usual dilution: 5 mg/mL

Infusion time: 15-60 minutes
Infusion rate: do not exceed 160 mg/minute because of calcium content 

IV Continuous Infusion NO

(For neonatal dosages, refer to Neonatal IV Drug Manual.)

"Rescue" Therapy after Methotrexate Administration:

  • Dose and schedule vary according to protocol and/or methotrexate serum level
  • Usual dose 10-15 mg/m2 q6h, beginning 24-48 hours after the start of methotrexate until serum methotrexate level falls below 1 x 10-7 M (0.1 microMolar).

Bleyer Nomogram for Delayed Elimination of Methotrexate:

48 Hour Methotrexate Level

Leucovorin Dose

<1 microMolar

10 mg/m2 q6h

<8 microMolar

100 mg/m2 q6h

>8 microMolar

1,000 mg/m2 q6h



Megaloblastic Anemia



  • 1 mg IM daily (doses greater than 1 mg have no greater efficacy)
Potential hazards of parenteral administration: 
  • Allergic reactions (rare)
  • Not to be used for the treatment of pernicious anemia or other megaloblastic anemias secondary to a Vitamin B12 deficiency (hematologic effects of Vitamin B12 deficiency may be masked, but neurologic abnormalities will not be prevented)
  • If serum creatinine is increased by more than 50% above baseline 24 hours after methotrexate administration, increase leucovorin dose to 100 mg/m2 q3h until serum methotrexate level falls below 5 x 10-8 Molar (0.05 microMolar) and obtain a nuclear GFR
  • High doses of methotrexate (>5 g/m2) are rescued at 24-36 hours
  • Intermediate doses of methotrexate (< 5 g/m2) are usually rescued at 42-48 hours
  • High doses of leucovorin may reduce the efficacy of intrathecally administered methotrexate

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