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 Warnings, Precautions, Pregnancy, Nursing, Abuse - Leucovorin
Leucovorin Warnings, Precautions, Pregnancy, Nursing, Abuse - Leucovorin
WARNINGS
In the treatment
of accidental overdosages of folic acid
antagonists, leucovorin should be administered as promptly as possible.
As the time interval between
antifolate administration
[eg, methotrexate
(MTX)] and leucovorin rescue increases, leucovorin's effectiveness
in counteracting toxicity diminishes.
Monitoring of serum MTX
concentration
is essential in determining
the optimal dose and duration
of treatment with
leucovorin.
Delayed MTX excretion
may be caused by a third space
fluid accumulation (ie,
ascites, pleural effusion),
renal insufficiency, or
inadequate hydration. Under such
circumstances, higher doses of leucovorin or prolonged administration
may be indicated. Doses higher than those recommended for oral
use must be given intravenously.
Leucovorin may enhance the toxicity
of fluorouracil. Deaths from severe enterocolitis, diarrhea,
and dehydration
have been reported in elderly patients receiving weekly leucovorin
and fluorouracil.1
Concomitant granulocytopenia
and fever were present
in some but not all of the patients.
Seizures and/or syncope
have been reported rarely in cancer
patients receiving leucovorin, usually in association
with fluoropyrimidine administration, and most commonly in those
with CNS metasteses or other
predisposing factors,
however, a causal relationship has not been established.2
PRECAUTIONS
General
Parenteral administration
is preferable to oral dosing
if there is a possibility that the patient
may vomit or not absorb
the leucovorin. Leucovorin has no
effect on other established
toxicities of MTX such
as the nephrotoxicity resulting from drug
and/or metabolite
precipitation
in the kidney.
Drug Interactions
Folic acid in large amounts
may counteract the
antiepileptic
effect of phenobarbital, phenytoin
and primidone, and increase the frequency
of seizures in susceptible
children.
Preliminary animal and
human studies have shown
that small quantities of systemically administered leucovorin enter
the CSF primarily as 5methyltetrahydrofolate
and, in humans, remain 13 orders of magnitude
lower than the usual methotrexate concentrations following intrathecal
administration. However, high doses of leucovorin may reduce
the efficacy of intrathecally
administered methotrexate.
Leucovorin may enhance the toxicity
of fluorouracil
(see WARNINGS
).
Pregnancy: Teratogenic Effects
"Pregnancy Category C." Animal reproduction
studies have not been conducted with leucovorin. It is also not
known whether leucovorin can cause
fetal harm when administered
to a pregnant woman
or can affect reproduction capacity. Leucovorin should be given
to a pregnant woman
only if clearly needed.
Nursing Mothers: It is not known whether this drug
is excreted in human milk.
Because many drugs are excreted in human
milk, caution should be exercised when leucovorin is administered
to a nursing mother.
Pediatric Use: see DRUG
INTERACTIONS.
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