Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2170
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Ondansetron (Injection)
|
| dailymed-instance:dosage |
Prevention of
Chemotherapy-Induced Nausea and Vomiting:: The
recommended intravenous dosage of Ondansetron Injection, USP is
a single 32 mg dose infused over 15 minutes beginning 30 minutes
before the start of emetogenic chemotherapy. The recommended
infusion rate should not be exceeded . Ondansetron
Injection, USP 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. Ondansetron
Injection, USP REQUIRES NO
DILUTION.<br/>Pediatric Use:: The
ondansetron premixed formulation is not recommended for use in
children. The ondansetron premixed formulation is a fixed dosage
form that has not been studied in the pediatric population, and
is not appropriate for weight based dosing in pediatric
patients.<br/>Geriatric Use:: 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/>Administration:: Ondansetron
Injection, USP is intended for intravenous infusion only. Parenteral
drug products should be inspected visually for particulate
matter and discoloration prior to administration whenever
solution and container permit. Do not use
if the solution is cloudy or precipitated or if the seal is not
intact. Consult with pharmacist for additive
compatibility. If additives are introduced, use
aseptic technique, mix thoroughly and use immediately. Ondansetron
Injection, USP 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/>Directions for Use:: Do not
remove unit from overwrap until ready for use. The overwrap is a
moisture barrier. The inner bag maintains the sterility of the
product.<br/>Caution:: Do not use
plastic containers in series connections. Such use could result
in air embolism due to residual air being drawn from the primary
container before administration of the fluid from the secondary
container is completed.<br/>To Open:: Tear
overwrap down side at slit and remove solution container. Some
opacity of the plastic due to moisture absorption during the
sterilization process may be observed. This is normal and does
not affect the solution quality or safety. The opacity will
diminish gradually. After removing overwrap, check for minute
leaks by squeezing inner bag firmly. If leaks are found, discard
unit as sterility may be impaired.<br/>Preparation for
Administration::<br/>Use aseptic
technique.: 1.
Suspend container from eyelet support. 2.
Remove protector from outlet port at bottom of
container. 3.
Attach administration set. Refer to complete directions
accompanying set.
|
| dailymed-instance:descripti... |
The active
ingredient in Ondansetron Injection, USP is Ondansetron Hydrochloride
USP, 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 365.86. Ondansetron
Hydrochloride, USP is a white to off-white powder that is soluble in
water and normal saline.<br/>Sterile, Premixed
Solution for Intravenous Administration in Single-Dose, Flexible
Plastic Containers:: A ready to
use iso-osmotic formulation of Ondansetron Injection, USP in 50
mL of sodium chloride diluent is available in the INTRAVIA
plastic container. Each 50 mL contains 32 mg ondansetron (as
Ondansetron Hydrochloride, USP); 450 mg Sodium Chloride, USP; 25
mg Citric Acid Monohydrate, USP; and 12.5 mg Sodium Citrate
Dihydrate, USP. Ondansetron Injection, USP is a clear,
colorless, nonpyrogenic sterile solution that contains no
preservatives. The pH is 3.3 to 4.0. The flexible plastic container is fabricated from a specially
designed multilayer plastic (PL 2408).
Solutions in contact with the plastic container leach out
certain of the chemical components from the plastic in very
small amounts; however the plastic container materials conform
to USP Biological Reactivity Testing requirements. The flexible
container has a foil overwrap. Water can permeate the plastic
into the overwrap, but the amount is insufficient to
significantly affect the premixed solution.
|
| dailymed-instance:clinicalP... |
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 emesis 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 emesis. 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 intravenous 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 emesis and nausea using the
ipecacuanha model of emesis. Both treatments were tolerated. 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 conjugations. 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 . In humans,
carmustine, etoposide, and cisplatin do not affect the
pharmacokinetics of ondansetron. In normal
volunteers, the following mean pharmacokinetic data have been
determined following a single 0.15-mg/kg intravenous dose. Geriatric:
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. Hepatic
Impairment: In patients with mild-to-moderate hepatic
impairment, clearance is reduced twofold and mean half-life is
increased to 11.6 hours compared to 5.7 hours in normals. In
patients with severe hepatic impairment (Child-Pugh
scoreof 10 or greater), clearance is reduced
twofold to threefold 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. Renal
Impairment: 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. Pediatric:
The pharmacokinetics of single dose 32 mg ondansetron pre-mixed
injection have not been characterized in pediatric patients. In normal
volunteers (19 to 39 years old, n = 23), the peak plasma
concentration was 264 ng/mL following a single 32-mg dose
administered as a 15-minute intravenous 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. 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.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Based on reports of
profound hypotension and loss of consciousness when apomorphine was
administered with ondansetron, the concomitant use of apomorphine with
ondansetron is contraindicated. Ondansetron
Injection, USP is contraindicated for patients known to have
hypersensitivity to the drug.
|
| dailymed-instance:supply |
Ondansetron
Injection, USP premix in INTRAVIA Plastic Containers is supplied as
follows: 2J1421 NDC
0338-1762-41 32 mg/50 mL 10 Pack<br/>Storage: Store
between 2��and 30��C (36��and 86��F). Brief exposure up to 40��C
(104��F) does not adversely affect the product. Protect from
light until immediately prior to use. Avoid excessive heat.
Protect from freezing.
|
| dailymed-instance:genericDr... | |
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:precautio... |
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/>Apomorphine:: Based on
reports of profound hypotension and loss of consciousness when
apomorphine was administered with ondansetron, the concomitant
use of apomorphine with ondansetron is
contraindicated.<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.<br/>Carcinogenesis,
Mutagenesis, Impairment of Fertility:: In a 2-year
oral carcinogenicity study in mice, ondansetron was not
carcinogenic at doses up to 30 mg/kg/day (about 3.8 times the
recommended human intravenous dose of 32 mg based on body
surface area). In a 2-year
oral carcinogenicity study in rats, ondansetron was not
carcinogenic at doses up to 10 mg/kg/day (about 2.5 times the
recommended human intravenous dose based on body surface area). Ondansetron
was not mutagenic in standard tests for mutagenicity. Ondansetron
at oral doses up to 15 mg/kg/day (about 3.8 times the
recommended human intravenous dose based on body surface area)
was found to have no effect on fertility and reproductive
performance of male or female rats.<br/>Pregnancy::<br/>Teratogenic
Effects::<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:: Ondansetron
premixed injection has not been studied in pediatric patients
and therefore is not recommended for use in children (seeDOSAGE AND
ADMINISTRATION section).<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).
|
| dailymed-instance:overdosag... |
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.
|
| dailymed-instance:genericMe... |
Ondansetron
|
| dailymed-instance:fullName |
Ondansetron (Injection)
|
| dailymed-instance:adverseRe... |
Chemotherapy-Induced Nausea and Vomiting:: The adverse
events in Table 6 have been reported in individuals 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 intravenous
fluids. Most were receiving a diuretic. 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 ondansetron 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 ondansetron
injection and rare cases of grand mal seizure. The relationship
to ondansetron injection was unclear.<br/>Other:: Rare cases
of hypokalemia have been reported. The relationship to
ondansetron injection was unclear.<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 opndansetron injection. Because they
are reported voluntarily from a population of unknown size,
estimates of frequency cannot be made. The events have been
chosen for inclusion due to a combination of their seriousness,
frequency of reporting, or potential causal connection to
ondansetron injection.<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 intravenous
infusion.<br/>Eye Disorders:: Transient blurred vision, in some cases associated with
abnormalities of accommodation. Rare cases of transient
blindness, predominantly during intravenous
administration, have been reported. These cases of
transient blindness were reported to resolve within a
few minutes up to 48 hours.
|
| dailymed-instance:warning |
Hypersensitivity
reactions have been reported in patients who have exhibited
hypersensitivity to other selective 5-HTreceptor
antagonists.
|
| dailymed-instance:indicatio... |
Prevention of
nausea and vomiting associated with initial and repeat courses of
emetogenic cancer chemotherapy in adult patients, including high-dose
cisplatin. Efficacy of the 32 mg single dose beyond 24 hours in these
patients has not been established.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Ondansetron
|