Leucovorin calcium tablets 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 (leucovorin calcium (leucovorin calcium (leucovorin calcium tablets) tablets) tablets) 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 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 then 25 mg should be
given parenterally (see CLINICAL PHARMACOLOGY).
Hydration (3L/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 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. 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.
Leucovorin Calcium (leucovorin calcium (leucovorin calcium (leucovorin calcium tablets) tablets) tablets) Tablets, USP are available as:
White, round, unscored, biconvex tablets. Debossed with stylized b on one side and 484 on the other side. Available in bottles of:
Pale green, round, unscored, biconvex tablets. Debossed with stylized b on
one side and 485 on the other side. Available in bottles of:
Protect from light and moisture.
Dispense with a child-resistant closure in a tight, light-resistant container.
Store at controlled room temperature 15°-25°C (59°-77°F) [See USP].
1. Grem JL, Shoemaker DD, Petrelli NJ, Douglas HO Jr: 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.
MANUFACTURED BY BARR LABORATORIES, INC. POMONA, NY 10970. OCTOBER
2002. FDA Rev date: 12/26/2000