Levoleucovorin Calcium Dosage
Applies to the following strengths: 50 mg; 175 mg; 10 mg/mL
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Usual Adult Dose for:
Additional dosage information:
Usual Adult Dose for Methotrexate Rescue
Levoleucovorin Rescue After High Dose Methotrexate Therapy:
Dose: 7.5 mg (approximately 5 mg/m2) IV every 6 hours for 10 doses starts 24 hours after the beginning of the methotrexate infusion. (The recommendations for levoleucovorin rescue are based on a methotrexate dose of 12 grams/m2 administered by intravenous infusion over 4 hours.)
Serum creatinine and methotrexate levels should be determined at least once daily. Levoleucovorin administration, hydration, and urinary alkalinization (pH of 7.0 or greater) should be continued until the methotrexate level is below 0.05 micromolar. The levoleucovorin dose should be adjusted or rescue extended based on the following guidelines:
Guidelines for Levoleucovorin Dosage and Administration
Clinical Situation 1) Normal Methotrexate Elimination
Laboratory Findings: Serum methotrexate level approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours.
Levoleucovorin Dosage and Duration: 7.5 mg IV every 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion).
Clinical Situation 2) Delayed Late Methotrexate Elimination
Laboratory Findings: Serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration.
Levoleucovorin Dosage and Duration: Continue 7.5 mg IV every 6 hours, until methotrexate level is less than 0.05 micromolar.
Clinical Situation 3) Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal Injury
Laboratory Findings: Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, or; a 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0.5 mg/dL to a level of 1 mg/dL or more).
Levoleucovorin Dosage and Duration: 75 mg IV every 3 hours until methotrexate level is less than 1 micromolar; then 7.5 mg IV every 3 hours until methotrexate level is less than 0.05 micromolar.
Patients who experience delayed early methotrexate elimination are likely to develop reversible renal failure. In addition to appropriate levoleucovorin therapy, these patients require continuing hydration, urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved.
Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe than the abnormalities described above. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, levoleucovorin rescue should be extended for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.
Delayed methotrexate excretion may be caused by accumulation in a third space fluid collection (i.e., ascites, pleural effusion), renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of levoleucovorin or prolonged administration may be indicated.
Although levoleucovorin may ameliorate the hematologic toxicity associated with high dose methotrexate, levoleucovorin has no effect on other established toxicities of methotrexate such as the nephrotoxicity resulting from drug and/or metabolite precipitation in the kidney.
Usual Adult Dose for Methotrexate Overdosage
Dosing Recommendations for Inadvertent Methotrexate Overdosage
Dose: 7.5 mg (approximately 5 mg/m2) should be administered IV every 6 hours until the serum methotrexate level is less than 10^-8 M.
Levoleucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion. As the time interval between antifolate administration (e.g., methotrexate) and levoleucovorin rescue increases, levoleucovorin effectiveness in counteracting toxicity may decrease.
Serum creatinine and methotrexate levels should be determined at 24 hour intervals. If the 24 hour serum creatinine has increased 50% over baseline or if the 24 hour methotrexate level is greater than 5 x 10^-6 M or the 48 hour level is greater than 9 x 10^-7 M, the dose of levoleucovorin should be increased to 50 mg/m2 IV every 3 hours until the methotrexate level is less than 10^-8 M. Hydration (3 L/day) and urinary alkalinization with NaHCO3 should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7.0 or greater.
Usual Adult Dose for Colorectal Cancer
For use in combination chemotherapy with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer:
Regimen 1: 100 mg/m2 by slow intravenous injection over a minimum of 3 minutes, followed by 5-FU at 370 mg/m2 by intravenous injection.
Regimen 2: 10 mg/m2 by intravenous injection followed by 5-FU at 425 mg/m2 by intravenous injection.
Treatment is repeated daily for five days. This five day treatment course may be repeated at 4 week (28 day) intervals, for 2 courses and then repeated at 4 to 5 week (28 to 35 day) intervals provided that the patient has completely recovered from the toxic effects of the prior treatment course.
In subsequent treatment courses, the dosage of 5-FU should be adjusted based on patient tolerance of the prior treatment course. The daily dosage of 5-FU should be reduced by 20% for patients who experienced moderate hematologic or gastrointestinal toxicity in the prior treatment course, and by 30% for patients who experienced severe toxicity. For patients who experienced no toxicity in the prior treatment course, 5-FU dosage may be increased by 10%. Levoleucovorin dosages are not adjusted for toxicity.
Renal Dose Adjustments
Data not available
Liver Dose Adjustments
Data not available
Levoleucovorin is dosed at one-half the usual dose of the racemic form.
Levoleucovorin is indicated for intravenous administration only. Do not administer intrathecally.
Due to the risk of precipitation, do not coadministered levoleucovorin with other agents in the same admixture.
No more than 16 mL of reconstituted solutions (160 mg of levoleucovorin) should be injected intravenously per minute, because of the calcium content of the levoleucovorin solution.
Data not available
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Other brands: Fusilev