Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3715
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ZOFRAN (Injection)
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Prevention of Chemotherapy-Induced Nausea and Vomiting:<br/>Adult Dosing: The recommended I.V.
dosage of ZOFRAN for adults is a single 32-mg dose or three 0.15-mg/kg doses.
A single 32-mg dose is infused over 15 minutes beginning 30 minutes
before the start of emetogenic chemotherapy. The recommended infusion rate
should not be exceeded (see OVERDOSAGE). With the three-dose (0.15-mg/kg)
regimen, the first dose is infused over 15 minutes beginning 30 minutes
before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg)
are administered 4 and 8 hours after the first dose of ZOFRAN. ZOFRAN
Injection should not be mixed with solutions for which physical and chemical
compatibility have not been established. In particular, this applies to alkaline
solutions as a precipitate may form.<br/>Vial: DILUTE BEFORE USE FOR PREVENTION
OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING. ZOFRAN Injection should
be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride
Injection before administration.<br/>Flexible Plastic Container: REQUIRES NO DILUTION.
ZOFRAN Injection Premixed, 32 mg in 5% Dextrose, 50 mL.<br/>Pediatric Dosing: On the basis of the available
information (see CLINICAL TRIALS: Pediatric Studies and CLINICAL PHARMACOLOGY:
Pharmacokinetics), the dosage in pediatric cancer patients 6 months to
18 years of age should be three 0.15-mg/kg doses. The first dose is to
be administered 30 minutes before the start of moderately to highly emetogenic
chemotherapy, subsequent doses (0.15 mg/kg) are administered 4 and 8 hours
after thefirst dose of ZOFRAN. The drug should be infused intravenously over
15 minutes. Little information is available about dosage in pediatric
cancer patients younger than 6 months of age.<br/>Vial: DILUTE BEFORE USE. ZOFRAN
Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9%
Sodium Chloride Injection before administration.<br/>Flexible Plastic Container: REQUIRES NO DILUTION.
ZOFRAN Injection Premixed, 32 mg in 5% Dextrose, 50 mL.<br/>Geriatric Dosing: The dosage recommendation is the same as for the general
population.<br/>Prevention of Postoperative Nausea and Vomiting:<br/>Adult Dosing: The recommended I.V. dosage of ZOFRAN for adults is 4 mg undiluted administered intravenously in not less
than 30 seconds, preferably over 2 to 5 minutes, immediately before
induction of anesthesia, or postoperatively if the patient experiences nausea
and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as
a single injection for adults. While recommended as a fixed dose for patients
weighing more than 40 kg, few patients above 80 kg have been studied.
In patients who do not achieve adequate control of postoperative nausea and
vomiting following a single, prophylactic, preinduction, I.V. dose of ondansetron
4 mg, administration of a second I.V. dose of 4 mg ondansetron postoperatively
does not provide additional control of nausea and vomiting.<br/>Vial: REQUIRES NO DILUTION FOR ADMINISTRATION
FOR POSTOPERATIVE NAUSEA AND VOMITING.<br/>Pediatric Dosing: The recommended I.V. dosage of ZOFRAN for pediatric surgical
patients (1 month to 12 years of age) is a single 0.1-mg/kg dose
for patients weighing 40 kg or less, or a single 4-mg dose for patients
weighing more than 40 kg. The rate of administration should not be less
than 30 seconds, preferably over 2 to 5 minutes immediately prior
to or following anesthesia induction, or postoperatively if thepatient experiences
nausea and/or vomiting occurring shortly after surgery. Prevention of further
nausea and vomiting was only studied in patients who had not received prophylactic
ZOFRAN.<br/>Vial: REQUIRES NO DILUTION FOR ADMINISTRATION
FOR POSTOPERATIVE NAUSEA AND VOMITING.<br/>Geriatric Dosing: The dosage recommendation is the same as for the general
population.<br/>Dosage Adjustment for Patients With Impaired Renal Function: The dosage recommendation is the same as for the general
population. There is no experience beyond first-day administration of ondansetron.<br/>Dosage Adjustment for Patients With Impaired Hepatic Function: In patients with severe hepatic impairment (Child-Pughscore
of 10 or greater), a single maximal daily dose of 8 mg to be infused
over 15 minutes beginning 30 minutes before the start of the emetogenic
chemotherapy is recommended. There is no experience beyond first-day administration
of ondansetron.<br/>ZOFRAN Injection Premixed in Flexible Plastic Containers:<br/>Instructions for Use:<br/>To Open: Tear outer wrap at notch and remove solution container.
Check for minute leaks by squeezing container firmly. If leaks are found,
discard unit as sterility may be impaired.<br/>Preparation for Administration: Use aseptic technique.<br/>Caution: ZOFRAN Injection Premixed in flexible plastic containers
is to be administered by I.V. drip infusion only. ZOFRAN Injection Premixed
should not be mixed with solutions for which physical and chemical compatibility
have not been established. In particular, this applies to alkaline solutions
as a precipitate may form. If used with a primary I.V. fluid system, the primary
solution should be discontinued during ZOFRAN Injection Premixed infusion. Do
not administer unless solution is clear and container is undamaged.<br/>Warning: Do not use flexible plastic container in series connections.<br/>Stability: ZOFRAN Injection is stable at room temperature under normal
lighting conditions for 48 hours after dilution with the following I.V.
fluids: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose
and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride
Injection, and 3% Sodium Chloride Injection. Although
ZOFRAN Injection is chemically and physically stable when diluted as recommended,
sterile precautions should be observed because diluents generally do not contain
preservative. After dilution, do not use beyond 24 hours.<br/>Note: Parenteral drug products should be inspected visually for
particulate matter and discoloration before administration whenever solution
and container permit.<br/>Precaution: Occasionally, ondansetron precipitates at the stopper/vial
interface in vials stored upright. Potency and safety are not affected. If
a precipitate is observed, resolubilize by shaking the vial vigorously.
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The active ingredient in ZOFRAN Injection and ZOFRAN Injection
Premixed is ondansetron hydrochloride (HCl), the racemic form of ondansetron
and a selective blocking agent of the serotonin 5-HTreceptor
type. Chemically it is (��) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one,
monohydrochloride, dihydrate. It has the following structural formula: The
empirical formula is CHNO���HCl���2HO,
representing a molecular weight of 365.9. Ondansetron
HCl is a white to off-white powder that is soluble in water and normal saline.<br/>Sterile Injection for Intravenous (I.V.) or Intramuscular (I.M.) Administration: Each 1 mL of aqueous
solution in the 2-mL single-dose vial contains 2 mg of ondansetron as
the hydrochloride dihydrate; 9.0 mg of sodium chloride, USP; and 0.5 mg
of citric acid monohydrate, USP and 0.25 mg of sodium citrate dihydrate,
USP as buffers in Water for Injection, USP. Each 1 mL of aqueous solution in the 20-mL
multidose vial contains 2 mg of ondansetron as the hydrochloride dihydrate;
8.3 mg of sodium chloride, USP; 0.5 mg of citric acid monohydrate,
USP and 0.25 mg of sodium citrate dihydrate, USP as buffers; and 1.2 mg
of methylparaben, NF and 0.15 mg of propylparaben, NF as preservatives
in Water for Injection, USP. ZOFRAN Injection is a
clear, colorless, nonpyrogenic, sterile solution. The pH of the injection
solution is 3.3 to 4.0.<br/>Sterile, Premixed Solution for Intravenous Administration in Single-Dose,
Flexible Plastic Containers: Each 50 mL contains ondansetron 32 mg (as the
hydrochloride dihydrate); dextrose 2,500 mg; and citric acid 26 mg
and sodium citrate 11.5 mg as buffers in Water for Injection, USP. It
contains no preservatives. The osmolarity of this solution is 270 mOsm/L
(approx.), and the pH is 3.0 to 4.0. The flexible plastic
container is fabricated from a specially formulated, nonplasticized, thermoplastic
co-polyester (CR3). Water can permeate from inside the container into the
overwrap but not in amounts sufficient to affect the solution significantly.
Solutions inside the plastic container also can leach out certain of the chemical
components in very small amounts before the expiration period is attained.
However, the safety of the plastic has been confirmed by tests in animals
according to USP biological standards for plastic containers.
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Pharmacodynamics: Ondansetron is a selective 5-HTreceptor antagonist.
While ondansetron's mechanism of action has not been fully characterized,
it is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HTtype
are present both peripherally on vagal nerve terminals and centrally in the
chemoreceptor trigger zone of the area postrema. It is not certain whether
ondansetron's antiemetic action in chemotherapy-induced nausea and vomiting
is mediated centrally, peripherally, or in both sites. However, cytotoxic
chemotherapy appears to be associated with release of serotonin from the enterochromaffin
cells of the small intestine. In humans, urinary 5-HIAA (5-hydroxyindoleacetic
acid) excretion increases after cisplatin administration in parallel with
the onset of vomiting. The released serotonin may stimulate the vagal afferents
through the 5-HTreceptors and initiate the vomiting reflex. In
animals, the emetic response to cisplatin can be prevented by pretreatment
with an inhibitor of serotonin synthesis, bilateral abdominal vagotomy and
greater splanchnic nerve section, or pretreatment with a serotonin 5-HTreceptor
antagonist. In normal volunteers, single I.V. doses
of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric
motility, lower esophageal sphincter pressure, or small intestinal transit
time. In another study in six normal male volunteers, a 16-mg dose infused
over 5 minutes showed no effect of the drug on cardiac output, heart
rate, stroke volume, blood pressure, or electrocardiogram (ECG). Multiday
administration of ondansetron has been shown to slow colonic transit in normal
volunteers. Ondansetron has no effect on plasma prolactin concentrations. In
a gender-balanced pharmacodynamic study (n = 56), ondansetron 4 mg
administered intravenously or intramuscularly was dynamically similar in the
prevention of nausea and vomiting using the ipecacuanha model of emesis. Ondansetron
does not alter the respiratory depressant effects produced by alfentanil or
the degree of neuromuscular blockade produced by atracurium. Interactions
with general or local anesthetics have not been studied.<br/>Pharmacokinetics: Ondansetron is extensively metabolized in humans, with approximately
5% of a radiolabeled dose recovered as the parent compound from the urine.
The primary metabolic pathway is hydroxylation on the indole ring followed
by glucuronide or sulfate conjugation. Although some
nonconjugated metabolites have pharmacologic activity, these are not found
in plasma at concentrations likely to significantly contribute to the biological
activity of ondansetron. In vitro metabolism studies
have shown that ondansetron is a substrate for human hepatic cytochrome P-450
enzymes, including CYP1A2, CYP2D6, and CYP3A4. In terms of overall ondansetron
turnover, CYP3A4 played the predominant role. Because of the multiplicity
of metabolic enzymes capable of metabolizing ondansetron, it is likely that
inhibition or loss of one enzyme (e.g., CYP2D6 genetic deficiency) will be
compensated by others and may result in little change in overall rates of
ondansetron elimination. Ondansetron elimination may be affected by cytochrome
P-450 inducers. In a pharmacokinetic study of 16 epileptic patients maintained
chronically on CYP3A4 inducers, carbamazepine, or phenytoin, reduction in
AUC, C, and Tof ondansetron was observed.This
resulted in a significant increase in clearance. However, on the basis of
available data, no dosage adjustment for ondansetron is recommended (see PRECAUTIONS:
Drug Interactions). In humans, carmustine, etoposide,
and cisplatin do not affect the pharmacokinetics of ondansetron. In
normal adult volunteers, the following mean pharmacokinetic data have been
determined following a single 0.15-mg/kg I.V. dose. A reduction in clearance and increase in elimination half-life
are seen in patients over 75 years of age. In clinical trials with cancer
patients, safety and efficacy were similar in patients over 65 years of age
and those under 65 years of age; there was an insufficient number of patients
over 75 years of age to permit conclusions in that age-group. No dosage
adjustment is recommended in the elderly. In patients
with mild-to-moderate hepatic impairment, clearance is reduced 2-fold and
mean half-life is increased to 11.6 hours compared to 5.7 hours
in normals. In patients with severe hepatic impairment (Child-Pughscore
of 10 or greater), clearance is reduced 2-fold to 3-fold and apparent volume
of distribution is increased with a resultant increase in half-life to 20 hours.
In patients with severe hepatic impairment, a total daily dose of 8 mg
should not be exceeded. Due to the very small contribution
(5%) of renal clearance to the overall clearance, renal impairment was not
expected to significantly influence the total clearance of ondansetron. However,
ondansetron mean plasma clearance was reduced by about 41% in patients with
severe renal impairment (creatinine clearance<30 mL/min). This reduction
in clearance is variable and was not consistent with an increase in half-life.
No reduction in dose or dosing frequency in these patients is warranted. In
adult cancer patients, the mean elimination half-life was 4.0 hours,
and there was no difference in the multidose pharmacokinetics over a 4-day
period. In a study of 21 pediatric cancer patients (4 to 18 years
of age) who received three I.V. doses of 0.15 mg/kg of ondansetron at
4-hour intervals, patients older than 15 years of age exhibited ondansetron
pharmacokinetic parameters similar to those of adults. Patients 4 to 12 years
of age generally showed higher clearance and somewhat larger volume of distribution
than adults. Most pediatric patientsyounger than 15 years of age with
cancer had a shorter (2.4 hours) ondansetron plasma half-life than patients
older than 15 years of age. It is not known whether these differences
in ondansetron plasma half-life may result in differences in efficacy between
adults and some young pediatric patients (see CLINICAL TRIALS: Pediatric Studies). Pharmacokinetic
samples were collected from 74 cancer patients 6 to 48 months of age,
who received a dose of 0.15 mg/kg of I.V. ondansetron every 4 hours for 3
doses during a safety and efficacy trial. These data were combined with sequential
pharmacokinetics data from 41 surgery patients 1 month to 24 months
of age, who received a single dose of 0.1 mg/kg of I.V. ondansetron prior
to surgery with general anesthesia, and a population pharmacokinetic analysis
was performed on the combined data set. The results of this analysis are included
in Table 2 and are compared to the pharmacokinetic results in cancer patients
4 to 18 years of age. Population PK (Pharmacokinetic)
Patients: 64% cancer patients and 36% surgery patients. Based
on the population pharmacokinetic analysis, cancer patients 6 to 48 months
of age who receive a dose of 0.15 mg/kg of I.V. ondansetron every 4 hours
for 3 doses would be expected to achieve a systemic exposure (AUC) consistent
with the exposure achieved in previous pediatric studies in cancer patients
(4 to 18 years of age) at similar doses. In a
study of 21 pediatric patients (3 to 12 years of age) who were undergoing
surgery requiring anesthesia for a duration of 45 minutes to 2 hours,
a single I.V. dose of ondansetron, 2 mg (3 to 7 years) or 4 mg
(8 to 12 years), was administered immediately prior to anesthesia induction.
Mean weight-normalized clearance and volume of distribution values in these
pediatric surgical patients were similar to those previously reported for
young adults. Mean terminal half-life was slightly reduced in pediatric patients
(range, 2.5 to 3 hours) in comparison with adults (range, 3 to 3.5 hours). In
a study of 51 pediatric patients (1 month to 24 months of age)
who were undergoing surgery requiring general anesthesia, a single I.V. dose
of ondansetron, 0.1 or 0.2 mg/kg, was administered prior to surgery.
As shown in Table 3, the 41 patients with pharmacokinetic data were divided
into 2 groups, patients1 month to 4 months of age and patients
5 to 24 months of age, and are compared to pediatric patients 3 to 12 years
of age. In general, surgical and cancer pediatric patients younger
than 18 years tend to have a higher ondansetron clearance compared to
adults leading to a shorter half-life in most pediatric patients. In patients
1 month to 4 months of age, a longer half-life was observed due
to the higher volume of distribution in this age group. In
normal volunteers (19 to 39 years old, n = 23), the peak plasmaconcentration was 264 ng/mL following a single 32-mg dose administered
as a 15-minute I.V. infusion. The mean elimination half-life was 4.1 hours.
Systemic exposure to 32 mg of ondansetron was not proportional to dose
as measured by comparing dose-normalized AUC values to an 8-mg dose. This
is consistent with a small decrease in systemic clearance with increasing
plasma concentrations. A study was performed in normal
volunteers (n = 56) to evaluate the pharmacokinetics of a single
4-mg dose administered as a 5-minute infusion compared to a single intramuscular
injection. Systemic exposure as measured by mean AUC was equivalent, with
values of 156 [95% CI 136, 180] and 161 [95% CI 137, 190] ng���h/mL for
I.V. and I.M. groups, respectively. Mean peak plasma concentrations were 42.9
[95% CI 33.8, 54.4] ng/mL at 10 minutes after I.V. infusion and 31.9
[95% CI 26.3, 38.6] ng/mL at 41 minutes after I.M. injection. The mean
elimination half-life was not affected by route of administration. Plasma
protein binding of ondansetron as measured in vitro was 70% to 76%, with binding
constant over the pharmacologic concentration range (10 to 500 ng/mL).
Circulating drug also distributes into erythrocytes. A
positive lymphoblast transformation test to ondansetron has been reported,
which suggests immunologic sensitivity to ondansetron.
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ZOFRAN Injection and ZOFRAN Injection Premixed are contraindicated
for patients known to have hypersensitivity to the drug.
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ZOFRAN Injection, 2 mg/mL,
is supplied as follows: NDC 0173-0442-02 2-mL single-dose
vials (Carton of 5) NDC 0173-0442-00 20-mL multidose
vials (Singles) Store between
2��and 30��C (36��and 86��F). Protect from light. ZOFRAN Injection Premixed, 32 mg/50 mL,
in 5% Dextrose, contains no preservatives and is supplied as a sterile, premixed
solution for I.V. administration in single-dose, flexible plastic containers
(NDC 0173-0461-00) (case of 6). Store
between 2��and 30��C (36��and 86��F). Protect from light.
Avoid excessive heat. Protect from freezing.
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General: Ondansetron is not a drug that stimulates gastric or intestinal
peristalsis. It should not be used instead of nasogastric suction. The use
of ondansetron in patients following abdominal surgery or in patients with
chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or
gastric distention. Rarely and predominantly with intravenous
ondansetron, transient ECG changes including QT interval prolongation have
been reported.<br/>Drug Interactions: Ondansetron does not itself appear to induce or inhibit
the cytochrome P-450 drug-metabolizing enzyme system of the liver (see CLINICAL
PHARMACOLOGY: Pharmacokinetics). Because ondansetron is metabolized by hepatic
cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers
or inhibitors of these enzymes may change the clearance and, hence, the half-life
of ondansetron. On the basis of limited available data, no dosage adjustment
is recommended for patients on these drugs.<br/>Phenytoin, Carbamazepine, and Rifampicin: In patients treated with potent inducers of CYP3A4 (i.e.,
phenytoin, carbamazepine, and rifampicin), the clearance of ondansetron was
significantly increased and ondansetron blood concentrations were decreased.
However, on the basis of available data, no dosage adjustment for ondansetron
is recommended for patients on these drugs.<br/>Tramadol: Although no pharmacokinetic drug interaction between ondansetron
and tramadol has been observed, data from 2 small studies indicate that ondansetron
may be associated with an increase in patient controlled administration of
tramadol.<br/>Chemotherapy: Tumor response to chemotherapy in the P 388 mouse leukemia
model is not affected by ondansetron. In humans, carmustine, etoposide, and
cisplatin do not affect the pharmacokinetics of ondansetron. In
a crossover study in 76 pediatric patients, I.V. ondansetron did not increase
blood levels of high-dose methotrexate.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenic effects were not seen in 2-year studies in
rats and mice with oral ondansetron doses up to 10 and 30 mg/kg per day,
respectively. Ondansetron was not mutagenic in standard tests for mutagenicity.
Oral administration of ondansetron up to 15 mg/kg per day did not affect
fertility or general reproductive performance of male and female rats.<br/>Pregnancy:<br/>Teratogenic Effects: Pregnancy Category
B. Reproduction studies have been performed in pregnant rats and rabbits at
I.V. doses up to 4 mg/kg per day and have revealed no evidence of impaired
fertility or harm to the fetus due to ondansetron. 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.<br/>Nursing Mothers: Ondansetron is excreted in the breast milk of rats. It is
not known whether ondansetron is excreted in human milk. Because many drugs
are excreted in human milk, caution should be exercised when ondansetron is
administered to a nursing woman.<br/>Pediatric Use: Little information is available about the use of ondansetron
in pediatric surgical patients younger than 1 month of age. (See CLINICAL
TRIALS section for studies of ondansetron in prevention of postoperative nausea
and vomiting in patients 1 month of age and older.) Little information
is available about the use of ondansetron in pediatric cancer patients younger
than 6 months of age. (See CLINICAL TRIALS section for studies of ondansetron
in chemotherapy-induced nausea and vomiting in pediatric patients 6 months
of age and older.) (See DOSAGE AND ADMINISTRATION.) The
clearance of ondansetron in pediatric patients 1 month to 4 months of age
is slower and the half-life is ~2.5 fold longer than patients who are>4 to
24 months of age. As a precaution, it is recommended that patients less than
4 months of age receiving this drug be closely monitored. (See CLINICAL PHARMACOLOGY:
Pharmacokinetics). The frequency and type of adverse
events reported in pediatric patients receiving ondansetron were similar to
those in patients receiving placebo. (See ADVERSE EVENTS.)<br/>Geriatric Use: Of the total number of subjects enrolled in cancer chemotherapy-induced
and postoperative nausea and vomiting in US- and foreign-controlled clinical
trials, 862 were 65 years of age and over. No overall differences in safety
or effectiveness were observed between these subjects and younger subjects,
and other reported clinical experience has not identified differences in responses
between the elderly and younger patients, but greater sensitivity of some
older individuals cannot be ruled out. Dosage adjustment is not needed in
patients over the age of 65 (see CLINICAL PHARMACOLOGY).
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There is no specific antidote for ondansetron overdose.
Patients should be managed with appropriate supportive therapy. Individual
doses as large as 150 mg and total daily dosages (three doses) as large
as 252 mg have been administered intravenously without significant adverse
events. These doses are more than 10 times the recommended daily dose. In
addition to the adverse events listed above, the following events have been
described in the setting of ondansetron overdose:���Sudden blindness���(amaurosis) of 2 to 3 minutes' duration plus severe constipation
occurred in one patient that was administered 72 mg of ondansetron intravenously
as a single dose. Hypotension (and faintness) occurred in another patient
that took 48 mg of oral ondansetron. Following infusion of 32 mg
over only a 4-minute period, a vasovagal episode with transient second-degree
heart block was observed. In all instances, the events resolved completely.
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ondansetron hydrochloride
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ZOFRAN (Injection)
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Chemotherapy-Induced Nausea and Vomiting: The adverse events in
Table 12 have been reported in adults receiving ondansetron at a dosage of
three 0.15-mg/kg doses or as a single 32-mg dose in clinical trials. These
patients were receiving concomitant chemotherapy, primarily cisplatin, and
I.V. fluids. Most were receiving a diuretic. * See Neurological. The
following have been reported during controlled clinical trials:<br/>Cardiovascular: Rare cases of angina (chest pain), electrocardiographic
alterations, hypotension, and tachycardia have been reported. In many cases,
the relationship to ZOFRAN Injection was unclear.<br/>Gastrointestinal: Constipation has been reported in 11% of chemotherapy patients
receiving multiday ondansetron.<br/>Hepatic: In comparative trials in cisplatin chemotherapy patients
with normal baseline values of aspartate transaminase (AST) and alanine transaminase
(ALT), these enzymes have been reported to exceed twice the upper limit of
normal in approximately 5% of patients. The increases were transient and did
not appear to be related to dose or duration of therapy. On repeat exposure,
similar transient elevations in transaminase values occurred in some courses,
but symptomatic hepatic disease did not occur.<br/>Integumentary: Rash has occurred in approximately 1% of patients receiving
ondansetron.<br/>Neurological: There have been rare reports consistent with, but not diagnostic
of, extrapyramidal reactions in patients receiving ZOFRAN Injection, and rare
cases of grand mal seizure. The relationship to ZOFRAN was unclear.<br/>Other: Rare cases of hypokalemia have been reported. The relationship
to ZOFRAN Injection was unclear.<br/>Postoperative Nausea and Vomiting: The adverse events in Table 13 have been reported in���2%
of adults receiving ondansetron at a dosage of 4 mg I.V. over 2 to 5 minutes
in clinical trials. Rates of these events were not significantly different
in the ondansetron and placebo groups. These patients were receiving multiple
concomitant perioperative and postoperative medications. * Sites of pain included abdomen,
stomach, joints, rib cage, shoulder.<br/>Pediatric Use: The adverse events in Table 14were the most commonly reported adverse events in pediatric patients
receiving ondansetron (a single 0.1-mg/kg dose for pediatric patients weighing
40 kg or less, or 4 mg for pediatric patients weighing more than40 kg) administered intravenously over at least 30 seconds. Rates
of these events were not significantly different in the ondansetron and placebo
groups. These patients were receiving multiple concomitant perioperative and
postoperative medications. The adverse events in Table 15 were the most commonly
reported adverse events in pediatric patients, 1 month to 24 months of
age, receiving a single 0.1-mg/kg I.V. dose of ondansetron. The incidence
and type of adverse events were similar in both the ondansetron and placebo
groups. These patients were receiving multiple concomitant perioperative and
postoperative medications.<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical trials,
the following events have been identified during post-approval use of intravenous
formulations of ZOFRAN. Because they are reported voluntarily from a population
of unknown size, estimates of frequency cannot be made. The events have been
chosenfor inclusion due to a combination of their seriousness, frequency
of reporting, or potential causal connection to ZOFRAN.<br/>Cardiovascular: Arrhythmias (including ventricular and supraventricular
tachycardia, premature ventricular contractions, and atrial fibrillation),
bradycardia, electrocardiographic alterations (including second-degree heart
block, QT interval prolongation, and ST segment depression), palpitations, and syncope.<br/>General: Flushing. Rare cases of hypersensitivity reactions, sometimes
severe (e.g., anaphylaxis/anaphylactoid reactions, angioedema, bronchospasm,
cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock,
shortness of breath, stridor) have also been reported.<br/>Hepatobiliary: Liver enzyme
abnormalities have been reported. Liver failure and death have been reported
in patients with cancer receiving concurrent medications including potentially
hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver
failure is unclear.<br/>Local Reactions: Pain, redness, and burning at site of injection.<br/>Lower Respiratory: Hiccups<br/>Neurological: Oculogyric crisis, appearing alone, as well as with other
dystonic reactions.<br/>Skin: Urticaria<br/>Special Senses: Transient dizziness during or shortly after I.V. infusion.
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| dailymed-instance:warning |
Hypersensitivity reactions have been reported in patients
who have exhibited hypersensitivity to other selective 5-HTreceptor
antagonists.
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ZOFRAN
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