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
Anzemet Warnings, Precautions, Pregnancy, Nursing, Abuse - Dolasetron
Anzemet Warnings, Precautions, Pregnancy, Nursing, Abuse - Dolasetron
WARNINGS
ANZEMET can cause
ECG interval
changes (PR, QTc, JT prolongation and QRS widening).
These changes are related in magnitude and frequency
to blood levels of the
active metabolite. These changes are self-limiting with declining
blood levels. Some patients
have interval prolongations for 24 hours or longer. Interval prolongation
could lead to cardiovascular
consequences, including heart
block or cardiac
arrhythmias. These have rarely been reported.
A cardiac conduction
abnormality observed
on an intra-operative cardiac rhythm monitor
(interpreted as complete heart
block) was reported in a 61 year old woman
who received 200 mg ANZEMET
for the prevention
of postoperative nausea and vomiting. This patient
was also taking verapamil. A similar event also interpreted as complete
heart block
was reported in one patient receiving placebo.
A 66-year-old man with Stage
IV non-Hodgkins lymphoma
died suddenly 6 hours after receiving 1.8 mg/kg (119 mg) intravenous
ANZEMET Injection. This patient had other potential
risk factors including
substantial exposure to doxorubicin and concomitant
cyclophosphamide.
PRECAUTIONS
General
Dolasetron should be administered with caution in patients who
have or may develop prolongation of cardiac
conduction intervals,
particularly QTc. These include patients with hypokalemia
or hypomagnesemia, patients taking diuretics with potential
for inducing electrolyte
abnormalities, patients with congenital
QT syndrome, patients
taking anti-arrhythmic drugs or other drugs which lead
to QT prolongation, and cumulative
high dose anthracycline therapy.
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis, Impairment
of Fertility
In a 24-month carcinogenicity study, there
was a statistically significant (P<0.001) increase in the incidence
of combined hepatocellular adenomas and carcinomas in male
mice treated with 150 mg/kg/day and above. In this study, mice (CD-1)
were treated orally with dolasetron mesylate 75, 150 or 300 mg/kg/day
(225, 450 or 900 mg/m2/day). For
a 50 kg person
of average height
(1.46 m2 body surface
area), these doses represent 3, 6, and 12 times the recommended
clinical dose (74 mg/m2)
on a body surface area
basis. No increase in liver
tumors was observed at a dose
of 75 mg/kg/day in male
mice and at doses up to 300 mg/kg/day in female
mice.
In a 24-month rat (Sprague-Dawley)
carcinogenicity study, oral
dolasetron mesylate was not tumorigenic
at doses up to 150 mg/kg/day (900 mg/m2/day,
12 times the recommended human
dose based on body
surface area) in male
rats and 300 mg/kg/day (1800 mg/m2/day,
24 times the recommended human
dose based on body
surface area) in female
rats.
Dolasetron mesylate was not genotoxic
in the Ames test, the rat
lymphocyte chromosomal aberration
test, the Chinese hamster
ovary (CHO) cell
(HGPRT) forward mutation
test, the rat hepatocyte
unscheduled DNA synthesis
(UDS) test or the mouse
micronucleus test.
Dolasetron mesylate was found to have no
effect on fertility
and reproductive performance at oral
doses up to 100 mg/kg/day (600 mg/m2/day,
8 times the recommended human
dose based on body
surface area) in female
rats and up to 400 mg/kg/day (2400 mg/m2/day,
32 times the recommended human
dose based on body
surface area) in male
rats.
Pregnancy
Teratogenic Effects. Pregnancy Category B. Teratology
studies have not revealed evidence
of impaired fertility or harm to the fetus
due to dolasetron mesylate. These studies have been performed in
pregnant rats at oral
doses up to 100 mg/kg/day (8 times the recommended human
dose based on body
surface area) and pregnant
rabbits at oral doses up
to 100 mg/kg/day (16 times the recommended human
dose based on body surface
area). There are, however, no
adequate and well-controlled studies in pregnant
women. Because animal
reproduction studies
are not always predictive of human
response, this drug should
be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether dolasetron mesylate is excreted in human
milk. Because many drugs are excreted in human
milk, caution should be exercised when ANZEMET Tablets are administered
to a nursing woman.
Pediatric Use
ANZEMET Tablets are expected to be as safe
and effective as when ANZEMET Injection is given orally to pediatric
patients. ANZEMET Tablets are recommended for children old enough
to swallow tablets (see
CLINICAL PHARMACOLOGY, Pharmacokinetics
in Humans).
Elderly
Dosage adjustment
is not needed in patients over 65. Effectiveness in prevention
of nausea and vomiting
in elderly patients was no
different than in younger age
groups.
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