LEUCOVORIN CALCIUM
Pronounciation
Trade Name(s)
May be given IV/IM or PO. If GI toxicity is present, should be administered parenterally.
Delayed excretion or overdose of methotrexate (MTX):
10 mg/M2 every 6 hours until the serum MTX level is less than 0.05 micromolar. Milligram for milligram or greater than the dose of MTX is common. Administer within the first hour (or as soon as possible) in overdose or within 24 hours of MTX dose if there is delayed excretion. At least every 24 hours, obtain a SCr and MTX level. If SCr is more than 50% above pretreatment level, increase the leucovorin dose to 100 mg/M2 every 3 hours until the serum MTX level is less than 0.05 micromolar.
Leucovorin rescue after high-dose MTX therapy:
With high-dose methotrexate (12 to 15 Gm/M2 as an infusion over 4 hours), begin leucovorin 15 mg (approximately 10 mg/M2) 24 hours after MTX infusion started. Repeat every 6 hours for 10 doses. If MTX elimination is delayed, extend every-6-hour dosing until MTX level is less than 0.05 micromolar. If there is evidence of acute renal injury, increase leucovorin to 150 mg every 3 hours until MTX level is less than 1 micromolar, then 15 mg every 3 hours until MTX level is less than 0.05 micromolar. In both situations obtain SCr and MTX level at least every 24 hours. Other protocols are in use. Amount of leucovorin is dependent on MTX dose, MTX serum levels, and SCr.
Megaloblastic anemia:
Up to 1 mg daily.
200 mg/M2 followed by fluorouracil (5-FU) 370 mg/M2 or leucovorin 20 mg/M2 followed by 5-FU 425 mg/M2 daily for 5 days. Repeat at 4-week intervals twice, then repeat every 28 to 35 days based on complete recovery from toxic effects. Reduce 5-FU dose based on tolerance to previous course, 20% for moderate hematologic or GI toxicity, 30% for severe. Leucovorin doses remain the same. Increase 5-FU dose 10% if no toxicity. Other protocols are in use. Also approved for use with irinotecan and 5-FU.
Pemetrexed toxicity (unlabeled):
A single dose of 100 mg/M2. Follow with 50 mg/M2 every 6 hours for 8 days.
See adjustments in Usual Dose; larger reductions may be required in the elderly based on the potential for decreased renal function, especially in combination with fluorouracil. ■ See Precautions/Monitor.
Each 50-mg, 100-mg, or 350-mg vial should be diluted to a 10 mg/mL to 20 mg/mL solution. For total doses less than 10 mg/M2, dilute with bacteriostatic water for injection (contains benzyl alcohol as a preservative). Use SWFI without a preservative for any dose 10 mg/M2 or greater. May be further diluted in 100 to 500 mL of D5W, D10W, NS, R, or LR. 1-mL (3-mg) ampules may be given undiluted (contain benzyl alcohol).
If prepared without a preservative, use immediately; stable up to 7 days with a preservative.
Several sources, including the manufacturer, cite incompatibility with fluorouracil (5-FU) as an additive; may form a precipitate.
Other sources suggest specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
Because of calcium content, do not exceed a rate of 160 mg/min (16 mL of a 10-mg/mL or 8 mL of a 20-mg/mL solution). May be given more slowly. Large doses may be infused equally distributed over 1 to 6 hours. Never exceed above limits.
Potent agent for neutralizing immediate toxic effects of methotrexate (and other folic acid antagonists) on the hematopoietic system. Preferentially rescues normal cells without reversing the oncolytic effect of methotrexate. Also enhances the therapeutic and toxic effects of fluoropyrimidines (e.g., fluorouracil).
Treatment of accidental folic acid antagonist (e.g., methotrexate) overdose or delayed excretion of MTX. ■ Folinic acid rescue to prevent or decrease the toxicity of massive MTX doses used to treat resistant neoplasms. ■ Treatment of megaloblastic anemia due to folic acid deficiency when oral therapy not appropriate. ■ In combination with fluorouracil or fluorouracil and irinotecan to treat colorectal cancer.
Adjunct in the treatment of Ewing’s sarcoma, head and neck cancer, non-Hodgkin lymphomas, and trophoblastic tumors. ■ Treatment of pemetrexed toxicity.
Pernicious anemia and other megaloblastic anemias secondary to lack of vitamin B12. None when used as indicated for other specific uses.
Usually administered in the hospital by or under the direction of the physician specialist. ■ Permits use of massive doses of methotrexate. ■ Do not discontinue leucovorin calcium until methotrexate serum levels fall below toxic levels. ■ Much less effective in accidental overdose after a 1-hour delay. ■ Delayed MTX excretion may occur from third-space fluid accumulation (ascites, pleural effusion), renal insufficiency, or inadequate hydration. ■ All doses over 25 mg should be given IM or IV (no more than 25 mg can be absorbed orally). ■ IM or IV dosing required in presence of GI toxicity, nausea, or vomiting. ■ Benzyl alcohol associated with gasping syndrome in premature infants.
Monitor serum blood levels of MTX and SCr levels at least daily until level is less than 0.05 micromolar. Death can occur in 5 to 10 days if MTX remains at toxic levels longer than 48 hours. ■ Minimum fluid intake of 3 L/24 hr and alkalinization of urine to a pH of 7 or more with oral sodium bicarbonate recommended. Begin 12 hours before MTX dose and continue for 48 hours after final dose in each sequence. Does not reduce nephrotoxicity of MTX from drug or metabolite precipitation in the kidney. ■ See methotrexate or fluorouracil monograph.
Category C: safety for use in pregnancy and breast-feeding not established. Benefits must outweigh risks. ■ Contains benzyl alcohol; do not use in neonates or dilute with SWFI if indicated; see Dilution.
Response similar to that seen in younger patients; however, use caution; may have greater sensitivity to its toxic effects (e.g., greater risk for GI toxicity and severe diarrhea in combination with fluorouracil). Monitoring of renal function suggested. ■ See Dose Adjustments.
May inhibit phenytoin, phenobarbital, and primidone; may cause increased frequency of seizures. ■ Is used in combination with fluorouracil; use caution; leucovorin calcium may increase toxic as well as therapeutic effects of fluorouracil. ■ When given with MTX, avoid any drug that may interfere with MTX elimination or binding to serum albumin (e.g., NSAIDs, probenecid, procarbazine, salicylates, sulfonamides). Consider as a possible cause of toxicity. ■ High doses of leucovorin may reduce the effectiveness of intrathecally administered methotrexate.■ Leucovorin may enhance the toxic effects of capecitabine; monitor closely. ■ Concurrent use with sulfamethoxazole and trimethoprim may cause treatment failure and increased morbidity in HIV patients being treated for Pneumocystis jiroveci pneumonia.
Allergic reactions including anaphylaxis have occurred rarely. Methotrexate or fluorouracil may cause many serious and dose-limiting side effects; see individual monographs.