Leucovorin (Leucovorin Calcium) - Indications and Dosage

INDICATIONS AND USAGE

Leucovorin Calcium Tablets USP are indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists.

DOSAGE AND ADMINISTRATION

Leucovorin calcium tablets are intended for oral administration. Because absorption is saturable, oral administration of doses greater than 25 mg is not recommended.

Impaired Methotrexate Elimination or Inadvertent Overdosage

Leucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion (see WARNINGS). Leucovorin 15 mg (10 mg/m²) should be administered IM, IV, or PO every 6 hours until the serum methotrexate level is less than 10^-8 M. In the presence of gastrointestinal toxicity, nausea, or vomiting, leucovorin should be administered parenterally.

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 leucovorin should be increased to 150 mg (100 mg/m²) IV every 3 hours until the methotrexate level is less than 10^-8 M. Doses greater than 25 mg should be given parenterally (see CLINICAL PHARMACOLOGY).

Hydration (3 L/d) and urinary alkalinization with sodium bicarbonate should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7.0 or greater.

The recommended dose of leucovorin to counteract hematologic toxicity from folic acid antagonists with less affinity for mammalian dihydrofolate reductase than methotrexate (i.e., trimethoprim, pyrimethamine) is substantially less, and 5 to 15 mg of leucovorin per day has been recommended by some investigators.

Patients who experience delayed early methotrexate elimination are likely to develop reversible non-oliguric renal failure. In addition to appropriate leucovorin therapy, these patients require continuing hydration and urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen 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. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, leucovorin rescue should be extended for an additional 24 hours (total 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.

HOW SUPPLIED

Leucovorin Calcium Tablets USP are available for oral administration as:

5 mg white, scored tablets (Identified 54 293).

NDC 0054-8496-19: Unit dose, 10 tablets per strip, 5 strips per shelf pack.

NDC 0054-4496-13: Bottles of 30 tablets.

NDC 0054-4496-25: Bottles of 100 tablets.

10 mg white, scored tablets (Identified 54 942).

NDC 0054-8497-06: Unit dose, 10 tablets per strip.

NDC 0054-4497-05: Bottles of 12 tablets.

NDC 0054-4497-10: Bottles of 24 tablets.

15 mg yellow, scored tablets (Identified 54 650).

NDC 0054-8498-06: Unit dose, 10 tablets per strip.

NDC 0054-4498-05: Bottles of 12 tablets.

NDC 0054-4498-10: Bottles of 24 tablets.

25 mg yellow, scored tablets (Identified 54 013).

NDC 0054-8499-06: Unit dose, 10 tablets per strip.

NDC 0054-4499-11: Bottles of 25 tablets.

Store at Controlled Room Temperature 15°-30°C (59°-86°F).

Protect From Light and Moisture.

References:

1. Grem JL, Shoemaker DD, Petrelli NJ, Douglas HO. Severe and fatal toxic effects observed in treatment with high- and low-dose leucovorin plus 5-fluorouracil for colorectal carcinoma. Cancer Treat Rep 1987;71:1122.
2. Link MP, Goorin AM, Miser AW et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 1986;314:1600-1606.

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© RLI, 2000