A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Leucovorin Indications, Dosage, Storage, Stability - Leucovorin
Leucovorin Indications, Dosage, Storage, Stability - Leucovorin
INDICATIONS
Leucovorin calcium
rescue is indicated after highdose methotrexate therapy in
osteosarcoma. Leucovorin is also 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.
Leucovorin Rescue after HighDose Methotrexate Therapy:
The recommendations for leucovorin rescue are based on a methotrexate
dose of 1215 grams/m2 administered
by intravenous infusion over 4 hours (see methotrexate
package insert for full prescribing information).3
Leucovorin rescue at a dose of 15 mg
(approximately 10 mg/m2) every 6
hours for 10 doses starts 24 hours after the beginning of the
methotrexate infusion. In
the presence of gastrointestinal
toxicity, nausea
or vomiting, leucovorin should be administered parenterally.
Serum creatinine
and methotrexate
levels should be determined at least once daily. Leucovorin administration,
hydration, and urinary
alkalinization (pH of 7.0 or greater) should be continued until
the methotrexate
level is below 5 x 10-8 M (0.05
micromolar). The leucovorin dose
should be adjusted or leucovorin rescue extended based on the following
guidelines:
GUIDELINES FOR LEUCOVORIN DOSAGE AND ADMINISTRATION
DO NOT ADMINISTER LEUCOVORIN INTRATHECALLY
| Clinical Situation |
Laboratory Findings |
Leucovorin Dosage and Duration |
| Normal Methotrexate Elimination |
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. |
15 mg
PO, IM, or IV q 6 hours
for 60 hours (10 doses starting at 24 hours after start of
methotrexate
infusion). |
| Delayed Late Methotrexate Elimination |
Serum methotrexate
level remaining above 0.2 micromolar at 72 hours, and more
than 0.05 micromolar at 96 hours after administration. |
Continue 15 mg
PO, IM, or IV q 6 hours,
until methotrexate level is less than 0.05 micromolar. |
| Delayed Early Methotrexate Elimination
and/or Evidence of Acute Renal Injury |
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
creatinie level at 24 hours after methotrexate administration
(eg, an increase from 0.5 mg/dL to a level of 1 mg/dL or more). |
150 mg
IV q 3 hours, until
methotrexate
level is less than 1 micromolar; then 15 mg
IV q 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
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 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
in the table above. 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 of 14 doses over 84 hours) in subsequent courses of therapy.
The possibility that the patient
is taking other medications which interact with methotrexate
(eg, medications which may interfere with methotrexate
elimination or binding
to serum albumin) should
always be reconsidered when laboratory
abnormalities or clinical toxicities are observed.
Impaired Methotrexate Elimination or Inadvertent OVERDOSAGE:
The same dosage and administration
guidelines may be used. However, leucovorin administration should
begin as soon as possible after an inadvertent overdosage is recognized.
HOW SUPPLIED
Leucovorin Calcium Tablets, 5 mg
are round, convex, yellowishwhite, engraved LL above 5 on one
side, scored in half on the other side
and engraved C above the score
and 33 below, each containing 5 mg
of leucovorin as the calcium salt,
supplied as follows:
NDC 58406-624-62 Bottle of 30 with CRC
NDC 58406-624-67 Bottle of 100
Leucovorin Calcium Tablets, 15 mg
are oval, convex, yellowishwhite, engraved LL on left
and 15 on right on one
side, scored in half on the other side
and engraved C to the left
of the score and 35 to
the right, each containing 15 mg
of leucovorin as the calcium
salt, supplied as follows:
NDC 58406-626-68 Bottle of 12 with CRC
NDC 58406-626-74 Bottle of 24 with CRC
STORE BETWEEN 15°30°C (59°86°F). PROTECT
FROM LIGHT.
REFERENCES
1. Grem, JL, Shoemaker, DD, Petrelli, NJ, Douglas, HO, "Severe
and Fatal Toxic Effects Observed in Treatment with High and
LowDose Leucovorin Plus 5Fluorouracil for Colorectal Carcinoma,"
Cancer Treat Rep 1987; 71:1122.
2. Meropol NJ, Creaven PJ, White RM, et al, "Seizures Associated
With Leucovorin Administration in Cancer Patients." JNCI
1995;87(1):56-58.
3. Link, MP, Goorin, AM, Miser, AW, et al, "The Effect of
Adjuvant Chemotherapy on RelapseFree Survival in Patients with
Osteosarcoma of the Extremity." N Engl J Med 1986;
314:16001606.
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