palonosetron
(injection)
Generic
Name: palonosetron (injection) (PAL oh NOE se tron)
Brand Name: Aloxi
Indications and Usage for Palonosetron Hydrochloride Injection
Chemotherapy-Induced
Nausea and Vomiting in Adults
Palonosetron Hydrochloride
(HCl) Injection is indicated for:
•
Moderately emetogenic cancer chemotherapy – prevention of acute and delayed
nausea and vomiting associated with initial and repeat courses
•
Highly emetogenic cancer chemotherapy – prevention of acute nausea and vomiting
associated with initial and repeat courses
Palonosetron Hydrochloride Injection Dosage and Administration
Recommended
Dosage
Chemotherapy-Induced Nausea and Vomiting
The recommended adult dosage
of Palonosetron HCl Injection is 0.25 mg administered as a single intravenous
dose over 30 seconds. Dosing should occur approximately 30 minutes before
the start of chemotherapy.
Instructions
for Intravenous Administration
Palonosetron HCl Injection is intended for direct
intravenous administration without further dilution.
Do not mix with other drugs.
When applicable, flush the line with normal saline
before and after administration of Palonosetron HCl Injection to ensure
complete dosing and to avoid drug incompatibilities.
Inspect Palonosetron HCl Injection visually for
particulate matter and discoloration before administration.
Dosage Forms and Strengths
Palonosetron Hydrochloride
Injection is sterile, clear, and colorless:
• 0.25 mg
palonosetron in 2 mL (0.125 mg/mL) in a single-dose vial
Contraindications
Palonosetron HCl Injection is
contraindicated in patients known to have hypersensitivity to the drug or any
of its components [see Adverse
Reactions (6.2)].
Warnings and Precautions
Hypersensitivity
Hypersensitivity reactions,
including anaphylaxis, have been reported with or without known
hypersensitivity to other 5-HT3 receptor antagonists.
Serotonin Syndrome
The development of serotonin
syndrome has been reported with 5-HT3 receptor antagonists. Most reports have been associated
with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake
inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs),
monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and
intravenous methylene blue). Some of the reported cases were fatal.
Serotonin syndrome occurring with overdose of another 5-HT3 receptor antagonist
alone has also been reported. The majority of reports of serotonin syndrome
related to 5-HT3 receptor antagonist use occurred in a post-anesthesia care
unit or an infusion center.
Symptoms associated with
serotonin syndrome may include the following combination of signs and symptoms:
mental status changes (e.g. agitation, hallucinations, delirium, and coma),
autonomic instability (e.g. tachycardia, labile blood pressure, dizziness,
diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor,
rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without
gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients
should be monitored for the emergence of serotonin syndrome, especially with
concomitant use of Palonosetron HCl Injection and other serotonergic
drugs. If symptoms of serotonin syndrome occur, discontinue Palonosetron
HCl Injection and initiate supportive treatment. Patients should be
informed of the increased risk of serotonin syndrome, especially if
Palonosetron HCl Injection is used concomitantly with other serotonergic
drugs [see Drug
Interactions (7.1)].
Adverse Reactions
Clinical
Trials Experience
Because clinical trials are
conducted under widely varying conditions, adverse reaction rates observed in
the clinical trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates reported in
practice.
The safety of Palonosetron HCl
Injection has been established from adequate and well-controlled studies of
another intravenous formulation of palonosetron HCl [see Clinical
Studies (14)]. Below is a display of the adverse reactions of
palonosetron HCl in these adequate and well-controlled studies.
Chemotherapy-Induced
Nausea and Vomiting
In clinical trials for the
prevention of nausea and vomiting induced by moderately or highly emetogenic
chemotherapy, 1374 adult patients received a single 0.25 mg dose of
palonosetron HCl. Adverse reactions were similar in frequency and severity with
intravenous palonosetron HCl and ondansetron or dolasetron.
The following is a listing of
all adverse reactions reported by ≥ 2% of patients in these trials (Table 1).
Table
1: Adverse Reactions from Chemotherapy-Induced Nausea and Vomiting Studies ≥ 2%
in any Treatment Group
|
Adverse Reaction
|
Palonosetron HCl
0.25 mg Intravenous
(N=633)
|
Ondansetron
32 mg Intraveneous
(N=410)
|
Dolasetron
100 mg Intraveneous
(N=194)
|
|
Headache
|
60 (9%)
|
34 (8%)
|
32 (16%)
|
|
Constipation
|
29 (5%)
|
8 (2%)
|
12 (6%)
|
|
Diarrhea
|
8 (1%)
|
7 (2%)
|
4 (2%)
|
|
Dizziness
|
8 (1%)
|
9 (2%)
|
4 (2%)
|
|
Fatigue
|
3 (< 1%)
|
4 (1%)
|
4 (2%)
|
|
Abdominal Pain
|
1 (< 1%)
|
2 (1%)
|
3 (2%)
|
|
Insomnia
|
1 (< 1%)
|
3 (1%)
|
3 (2%)
|
In other studies, 2 patients
experienced severe constipation following a single palonosetron HCl dose of
approximately 0.75 mg, three times the recommended dose.
In clinical trials, the
following infrequently reported adverse reactions, assessed by investigators as
treatment-related or causality unknown, occurred following administration of
palonosetron HCl to adult patients receiving concomitant cancer chemotherapy:
Cardiovascular: 1%: non-sustained tachycardia, bradycardia, hypotension, <
1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus
arrhythmia, supraventricular extrasystoles and QT prolongation. In many cases,
the relationship to palonosetron was unclear.
Dermatological: < 1%: allergic dermatitis, rash.
Hearing
and Vision: < 1%: motion
sickness, tinnitus, eye irritation and amblyopia.
Gastrointestinal
System: 1%: diarrhea, < 1%: dyspepsia,
abdominal pain, dry mouth, hiccups and flatulence.
General: 1%: weakness, < 1%: fatigue, fever, hot flash, flu-like
syndrome.
Liver: < 1%: transient, asymptomatic increases in AST and/or ALT
and bilirubin. These changes occurred predominantly in patients receiving
highly emetogenic chemotherapy.
Metabolic: 1%: hyperkalemia, < 1%: electrolyte fluctuations,
hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia.
Musculoskeletal: < 1%: arthralgia.
Nervous
System: 1%: dizziness, < 1%: somnolence,
insomnia, hypersomnia, paresthesia.
Psychiatric: 1%: anxiety, < 1%: euphoric mood.
Urinary
System: < 1%: urinary retention.
Vascular: < 1%: vein discoloration, vein distention.
Postmarketing
Experience
The following adverse
reactions have been identified during post approval use of another intravenous
formulation of palonosetron HCl. Because these reactions are reported
voluntarily from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship to drug
exposure.
Very rare cases (<1/10,000)
of hypersensitivity reactions including anaphylaxis and anaphylactic shock and
injection site reactions (burning, induration, discomfort and pain) were
reported from postmarketing experience of palonosetron HCl 0.25 mg in the
prevention of chemotherapy-induced nausea and vomiting.
Drug Interactions
Serotonergic
Drugs
Serotonin syndrome (including
altered mental status, autonomic instability, and neuromuscular symptoms) has
been described following the concomitant use of 5-HT3 receptor antagonists and
other serotonergic drugs, including selective serotonin reuptake inhibitors
(SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs).
Monitor for the emergence of serotonin syndrome. If symptoms occur,
discontinue Palonosetron HCl Injection and initiate supportive treatment [see Warnings
and Precautions (5.2)].
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
There are no available data on
palonosetron HCl use in pregnant women to inform a drug-associated risk. In
animal reproduction studies, no effects on embryo-fetal development were
observed with the administration of oral palonosetron HCl to rats and rabbits
during organogenesis at doses up to 1894 and 3789 times the recommended human
intravenous dose, respectively [see Data].
The estimated background risk
of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major
birth defects and miscarriage in clinically recognized pregnancies is 2 to 4%
and 15 to 20%, respectively.
Data
Animal
Data
In animal reproduction
studies, no effects on embryo-fetal development were observed in pregnant rats
given oral palonosetron HCl at doses up to 60 mg/kg/day (1894 times the
recommended human intravenous dose based on body surface area) or pregnant
rabbits given oral doses up to 60 mg/kg/day (3789 times the recommended human
intravenous dose based on body surface area) during the period of
organogenesis.
Lactation
Risk Summary
There are no data on the
presence of palonosetron in human milk, the effects of palonosetron on the
breastfed infant, or the effects of palonosetron on milk production. The
developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for Palonosetron HCl Injection and any
potential adverse effects on the breastfed infant from palonosetron or from the
underlying maternal condition.
Pediatric Use
This product has not been
approved for use in pediatric patients for prevention of chemotherapy-induced
nausea and vomiting.
Geriatric Use
Of the 1374 adult cancer
patients in clinical studies of intravenously administered palonosetron HCl for
CINV, 316 (23%) were aged 65 years and over, while 71 (5%) were aged 75 years
and over. No overall differences in safety or effectiveness were observed
between these subjects and the younger subjects, but greater sensitivity in
some older individuals cannot be ruled out. Population pharmacokinetics
analysis did not reveal any differences in palonosetron pharmacokinetics
between cancer patients aged 65 years and older and younger patients (18 to 64
years). No dose adjustment or special monitoring are required for
geriatric patients.
Overdosage
There is no known antidote to
palonosetron HCl. Overdose should be managed with supportive care.
Dialysis studies have not been
performed; however, due to the large volume of distribution, dialysis is
unlikely to be an effective treatment for palonosetron HCl overdose. A single
intravenous dose of palonosetron HCl at 30 mg/kg (947 and 474 times the human
dose for rats and mice, respectively, based on body surface area) was lethal to
rats and mice. The major signs of toxicity were convulsions, gasping, pallor,
cyanosis and collapse.
Palonosetron Hydrochloride Injection Description
Palonosetron Hydrochloride
Injection contains palonosetron as palonosetron HCl, an antiemetic and
antinauseant agent. It is a serotonin-3 (5-HT3) receptor antagonist with a
strong binding affinity for this receptor. Chemically, palonosetron HCl is:
(3aS)-2-[(S)-1-Azabicyclo [2.2.2]oct-3-yl]-2,3,3a,4,5,6 hexahydro-1-oxo-1Hbenz[de]isoquinoline
hydrochloride. The empirical formula is C19H24N2O•HCl, with a molecular weight
of 332.87. Palonosetron HCl exists as a single isomer and has the following
structural formula:
Palonosetron HCl is a white to
off-white crystalline powder. It is freely soluble in water, soluble in
propylene glycol, and slightly soluble in ethanol and 2-propanol.
Palonosetron HCl Injection is
a sterile, clear, colorless, non-pyrogenic, non-buffered, hypotonic solution
for intravenous administration. Palonosetron HCl Injection contains no
preservative or chelating agent. Palonosetron HCl Injection is available as 2
mL single-dose vial.
Each 2 mL vial contains 0.25
mg palonosetron base equivalent to 0.28 mg palonosetron HCl, and water for
intravenous administration.
The pH of the solution in the
2 mL vial is 6.5 to 8.5.
Palonosetron Hydrochloride Injection - Clinical Pharmacology
Mechanism of
Action
Palonosetron is a 5-HT3 receptor antagonist with
a strong binding affinity for this receptor and little or no affinity for other
receptors.
Cancer chemotherapy may be
associated with a high incidence of nausea and vomiting, particularly when
certain agents, such as cisplatin, are used. 5-HT3 receptors are located on
the nerve terminals of the vagus in the periphery and centrally in the
chemoreceptor trigger zone of the area postrema. It is thought that
chemotherapeutic agents produce nausea and vomiting by releasing serotonin from
the enterochromaffin cells of the small intestine and that the released
serotonin then activates 5-HT3receptors located on vagal afferents to initiate the vomiting
reflex.
Pharmacodynamics
Cardiac Electrophysiology
The effect of intravenous
palonosetron HCl on blood pressure, heart rate, and ECG parameters including
QTc were comparable to intravenous ondansetron and dolasetron in CINV clinical
trials. In non-clinical studies palonosetron possesses the ability to block ion
channels involved in ventricular de- and re-polarization and to prolong action
potential duration.
The effect of palonosetron on
QTc interval was evaluated in a double blind, randomized, parallel, placebo and
positive (moxifloxacin) controlled trial in adult men and women. The objective
was to evaluate the ECG effects of intravenously administered palonosetron HCl
at single doses of 0.25, 0.75 or 2.25 mg in 221 healthy subjects. At a dose 9
times the maximum recommended dose, palonosetron did not prolong the QT
interval to any clinically relevant extent.
Pharmacokinetics
After intravenous dosing of
palonosetron HCl in healthy subjects and cancer patients, an initial decline in
plasma concentrations is followed by a slow elimination from the body.
Mean maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-∞) are generally
dose-proportional over the dose range of 0.3 to 90 mcg/kg in healthy subjects
and in cancer patients. Following a single intravenous dose of palonosetron HCl
at 3 mcg/kg (or 0.21 mg/70 kg) to six cancer patients, the mean (±SD) maximum
plasma concentration was estimated to be 5630 ± 5480 ng/L and the mean AUC was
35.8 ± 20.9 h•mcg/L.
Following intravenous
administration of palonosetron HCl 0.25 mg once every other day for 3 doses in
11 cancer patients, the mean increase in plasma palonosetron concentration from
Day 1 to Day 5 was 42 ± 34%. Following intravenous administration of
palonosetron HCl 0.25 mg once daily for 3 days in 12 healthy subjects, the mean
(±SD) increase in plasma palonosetron concentration from Day 1 to Day 3 was 110
± 45%.
Distribution
Palonosetron has a volume of distribution of approximately 8.3 ± 2.5 L/kg.
Approximately 62% of palonosetron is bound to plasma proteins.
Elimination
After a single intravenous dose of 10 mcg/kg [14C]-palonosetron HCl,
approximately 80% of the dose was recovered within 144 hours in the urine with
palonosetron representing approximately 40% of the administered dose. In
healthy subjects, the total body clearance of palonosetron was 0.160 ± 0.035
L/h/kg and renal clearance was 0.067 ± 0.018 L/h/kg. The mean terminal
elimination half-life is approximately 40 hours.
Metabolism
Palonosetron is eliminated by multiple routes with approximately
50% metabolized to form two primary metabolites: N-oxide-palonosetron and
6-S-hydroxy-palonosetron. These metabolites each have less than 1% of the 5-HT3 receptor antagonist
activity of palonosetron. In vitro metabolism
studies have suggested that CYP2D6 and to a lesser extent, CYP3A4 and CYP1A2
are involved in the metabolism of palonosetron. However, clinical
pharmacokinetic parameters are not significantly different between poor and
extensive metabolizers of CYP2D6 substrates.
Excretion
Palonosetron is partially eliminated from the body through renal
excretion.
Specific
Populations
Renal Impairment
Mild to moderate renal impairment does not significantly affect
palonosetron pharmacokinetic parameters. Total systemic exposure increased by
approximately 28% in patients with severe renal impairment relative to healthy
subjects. This increase is not considered clinically meaningful.
Hepatic
Impairment
Hepatic impairment does not significantly affect total body
clearance of palonosetron compared to the healthy subjects.
Race/Ethnicity
The pharmacokinetics of palonosetron were characterized in
twenty-four healthy Japanese subjects over the dose range of 3 to 90
mcg/kg. Total body clearance was 25% higher in Japanese subjects compared
to Whites; however, no dose adjustment is required. The pharmacokinetics
of palonosetron in Blacks has not been adequately characterized.
Drug
Interaction Studies
In vitro studies indicated that palonosetron is not an inhibitor of
CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not
investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5.
Therefore, the potential for clinically significant drug interactions with
palonsetron appears to be low.
Dexamethasone
Coadministration of 0.25 mg palonosetron HCl and 20 mg
dexamethasone administered intravenously in healthy subjects revealed no
pharmacokinetic drug-interactions between palonosetron and dexamethasone.
Oral
Aprepitant
In an interaction study in healthy subjects where a single 0.25
mg intravenous dose of palonosetron HCl was administered on day 1 and oral
aprepitant for 3 days (125 mg/80 mg/80 mg), the pharmacokinetics of
palonosetron were not significantly altered (AUC: no change, Cmax: 15% increase).
Metoclopramide
A study in healthy subjects involving a single 0.75 mg
intravenous dose of palonosetron HCl and steady state oral metoclopramide (10
mg four times daily) demonstrated no significant pharmacokinetic interaction.
Corticosteroids,
Analgesics, Antiemetics/Antinauseants, Antispasmodics and Anticholinergic
Agents
In controlled clinical trials, palonosetron HCl has been safely
administered with corticosteroids, analgesics, antiemetics/antinauseants,
antispasmodics and anticholinergic agents.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 104-week carcinogenicity
study in CD-1 mice, animals were treated with oral doses of palonosetron HCl at
10, 30 and 60 mg/kg/day. Treatment with palonosetron was not tumorigenic. The
highest tested dose produced a systemic exposure to palonosetron (plasma AUC)
of about 150 to 289 times the human exposure (AUC = 29.8 h•mcg/L) at the
recommended intravenous dose of 0.25 mg. In a 104-week carcinogenicity study in
Sprague-Dawley rats, male and female rats were treated with oral doses of 15,
30 and 60 mg/kg/day and 15, 45 and 90 mg/kg/day, respectively. The highest
doses produced a systemic exposure to palonosetron (plasma AUC) of 137 and 308
times the human exposure at the recommended dose. Treatment with palonosetron
HCl produced increased incidences of adrenal benign pheochromocytoma and
combined benign and malignant pheochromocytoma, increased incidences of
pancreatic Islet cell adenoma and combined adenoma and carcinoma and pituitary
adenoma in male rats. In female rats, it produced hepatocellular adenoma and
carcinoma and increased the incidences of thyroid C-cell adenoma and combined
adenoma and carcinoma.
Palonosetron was not genotoxic
in the Ames test, the Chinese hamster ovarian cell (CHO/HGPRT) forward mutation
test, the ex vivo hepatocyte
unscheduled DNA synthesis (UDS) test or the mouse micronucleus test. It was,
however, positive for clastogenic effects in the Chinese hamster ovarian (CHO)
cell chromosomal aberration test.
Palonosetron HCl at oral doses
up to 60 mg/kg/day (about 1894 times the recommended human intravenous dose
based on body surface area) was found to have no effect on fertility and
reproductive performance of male and female rats.
Clinical Studies
The safety and efficacy of
Palonosetron HCl Injection have been established based on adequate and
well-controlled adult studies of another intravenous formulation of
palonosetron HCl in chemotherapy induced nausea and vomiting. Below is a
display of the results of these adequate and well-controlled studies of
palonosetron HCl.
Chemotherapy-Induced
Nausea and Vomiting
Efficacy of a single
intravenous dose of palonosetron HCl in preventing acute and delayed nausea and
vomiting induced by both moderately and highly emetogenic chemotherapy was
studied in 4 trials. In these double-blind trials, complete response rates (no
emetic episodes and no rescue medication) and other efficacy parameters were
assessed through at least 120 hours after administration of chemotherapy. The
safety and efficacy of palonosetron HCl in repeated courses of chemotherapy was
also assessed.
Moderately
Emetogenic Chemotherapy:
Two double-blind trials (Study
1 and Study 2) involving 1132 patients compared a single intravenous dose of
palonosetron HCl with either a single intravenous dose of ondansetron (Study 1)
or dolasetron (Study 2) given 30 minutes prior to moderately emetogenic
chemotherapy including carboplatin, cisplatin ≤ 50 mg/m², cyclophosphamide <
1500 mg/m², doxorubicin > 25 mg/m², epirubicin, irinotecan, and methotrexate
> 250 mg/m². Concomitant corticosteroids were not administered
prophylactically in Study 1 and were only used by 4 to 6% of patients in Study
2. The majority of patients in these studies were women (77%), White (65%) and
naïve to previous chemotherapy (54%). The mean age was 55 years.
Highly
Emetogenic Chemotherapy:
A double-blind, dose-ranging
trial evaluated the efficacy of single-dose intravenous palonosetron from 0.3
to 90 mcg/kg (equivalent to < 0.1 mg to 6 mg fixed dose) in 161
chemotherapy-naïve adult cancer patients receiving highly emetogenic
chemotherapy (either cisplatin ≥ 70 mg/m² or cyclophosphamide >1100 mg/m²).
Concomitant corticosteroids were not administered prophylactically. Analysis of
data from this trial indicates that 0.25 mg is the lowest effective dose in
preventing acute nausea and vomiting induced by highly emetogenic chemotherapy.
A double-blind trial involving
667 patients compared a single intravenous dose of palonosetron HCl with a
single intravenous dose of ondansetron (Study 3) given 30 minutes prior to
highly emetogenic chemotherapy including cisplatin ≥ 60 mg/m², cyclophosphamide
> 1500 mg/m², and dacarbazine. Corticosteroids were co-administered
prophylactically before chemotherapy in 67% of patients. Of the 667 patients, 51%
were women, 60% White, and 59% naïve to previous chemotherapy. The mean age was
52 years.
Efficacy
Results:
The antiemetic activity of
palonosetron HCl was evaluated during the acute phase (0-24 hours) [Table 3],
delayed phase (24-120 hours) [Table 4], and overall phase (0-120 hours) [Table
5] post-chemotherapy in Studies 1, 2 and 3.
Table
3: Prevention of Acute Nausea and Vomiting (0-24 hours): Complete Response
Rates
a Intent-to-treat cohort
b 2-sided
Fisher’s exact test. Significance level α=0.025.
c These
studies were designed to show non-inferiority. A lower bound greater than –15%
demonstrates non-inferiority between palonosetron HCl and comparator.
d Ondansetron
32 mg intravenous was used in the clinical trial. Although this dose was
used in the trial, this is no longer the currently recommended dose.
Refer to the ondansetron prescribing information for the current
recommended dose.
These trials show that
palonosetron HCl was effective in the prevention of acute nausea and vomiting
associated with initial and repeat courses of moderately and highly emetogenic
cancer chemotherapy.
In Study 3, efficacy was
greater when prophylactic corticosteroids were administered concomitantly.
Clinical superiority over other 5-HT3 receptor antagonists has not been adequately demonstrated
in the acute phase.
Table
4: Prevention of Delayed Nausea and Vomiting (24-120 hours): Complete Response
Rates
a Intent-to-treat cohort
b 2-sided
Fisher’s exact test. Significance level α=0.025.
c These
studies were designed to show non-inferiority. A lower bound greater than –15%
demonstrates non-inferiority between palonosetron HCl and comparator.
d Ondansetron
32 mg intravenous was used in the clinical trial. Although this dose was
used in the trial, this is no longer the currently recommended dose.
Refer to the ondansetron prescribing information for the current
recommended dose.
These trials show that
palonosetron HCl was effective in the prevention of delayed nausea and vomiting
associated with initial and repeat courses of moderately emetogenic
chemotherapy.
Table
5: Prevention of Overall Nausea and Vomiting (0-120 hours): Complete Response
Rates
a Intent-to-treat cohort
b 2-sided
Fisher’s exact test. Significance level α=0.025.
c These
studies were designed to show non-inferiority. A lower bound greater than –15%
demonstrates non-inferiority between palonosetron HCl and comparator.
d Ondansetron
32 mg intravenous was used in the clinical trial. Although this dose was
used in the trial, this is no longer the currently recommended dose.
Refer to the ondansetron prescribing information for the current
recommended dose.
These trials show that
palonosetron HCl was effective in the prevention of nausea and vomiting
throughout the 120 hours (5 days) following initial and repeat courses of
moderately emetogenic cancer chemotherapy.
How Supplied/Storage and Handling
How Supplied
Palonosetron Hydrochloride
Injection is clear and colorless and is supplied in single-dose vials as
follows:
NDC Number Strength
Package
0143-9513-01 0.25
mg/2 mL (0.125 mg/mL) 1 vial/carton
Storage
Store at 20° to 25°C (68° to 77°F); [Excursions
permitted to 15° to 30°C (59° to 86°F)].
Protect from freezing.
Protect from light.
Patient Counseling Information
Advise patients to read the
FDA-approved patient labeling (Patient
Information).
Hypersensitivity
Reactions
Advise patients that
hypersensitivity reactions, including anaphylaxis, have been reported in
patients with or without known hypersensitivity to other 5-HT3 receptor
antagonists. Advise patients to seek immediate medical attention if any
signs or symptoms of a hypersensitivity reaction occur with administration of
Palonosetron HCl Injection [see Warnings
and Precautions (5.1)].
Serotonin
Syndrome
Advise patients of the
possibility of serotonin syndrome, especially with concomitant use of
Palonsetron HCl Injection and another serotonergic agent such as medications to
treat depression and migraines. Advise patients to seek immediate medical
attention if the following symptoms occur: changes in mental status,
autonomic instability, neuromuscular symptoms with or without gastrointestinal
symptoms [see Warnings
and Precautions (5.2)].
Manufactured
by:
Exela Pharma Sciences LLC
Lenoir, NC 28645 USA
Distributed
by:
WEST-WARD
A HIKMA COMPANY
Eatontown, NJ 07724 USA
9513-0617-00
Issued June 2017
Patient
Information
Palonosetron Hydrochloride Injection (PAL-oh-NOE-se-tron
HYE-droe-KLOR-ide)
for intravenous use
Read this Patient Information
before you receive Palonosetron Hydrochloride Injection and each time you
receive Palonosetron Hydrochloride Injection. There may be new information.
This information does not take the place of talking with your doctor about your
medical condition or your treatment.
What
is Palonosetron Hydrochloride Injection?
Palonosetron Hydrochloride
Injection is a prescription medicine called an “antiemetic.”
Palonosetron Hydrochloride
Injection is used in adults to help prevent the nausea and vomiting that
happens right away or later with certain anti-cancer medicines (chemotherapy).
This product has not been
approved for use in children to help prevent nausea and vomiting after
chemotherapy.
Who
should not receive Palonosetron Hydrochloride Injection?
Do not receive Palonosetron
Hydrochloride Injection if you are allergic to palonosetron hydrochloride or
any of the ingredients in Palonosetron Hydrochloride Injection. See the end of
this leaflet for a complete list of ingredients in Palonosetron Hydrochloride
Injection.
What
should I tell my doctor before receiving Palonosetron Hydrochloride Injection?
Before
receiving Palonosetron Hydrochloride Injection, tell your doctor about all of
your medical conditions, including if you:
• have had an allergic
reaction to another medicine for nausea or vomiting
• are pregnant or plan to
become pregnant. It is not known if Palonosetron Hydrochloride Injection will
harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known
if Palonosetron Hydrochloride Injection passes into your breast milk or if it
will affect your baby or your breast milk. Talk to your doctor about the best
way to feed your baby if you will receive Palonosetron Hydrochloride Injection.
Tell
your doctor about all of the medicines you take including prescription and over-the-counter medicines,
vitamins and herbal supplements.
Palonosetron Hydrochloride
Injection and certain other medicines can affect each other, causing serious
side effects.
How
will I receive Palonosetron Hydrochloride Injection?
• Palonosetron Hydrochloride
Injection will be given to you in your vein by I.V. (intravenous) injection.
• Palonosetron Hydrochloride
Injection is usually given about 30 minutes before you receive your anti-cancer
medicine (chemotherapy).
What
are the possible side effects of Palonosetron Hydrochloride Injection?
Palonosetron
Hydrochloride Injection may cause serious side effects, including:
• Serious
allergic reactions. Palonosetron Hydrochloride Injection can
cause allergic reactions that can sometimes be serious. Tell your doctor or
nurse right away if you have any of the following symptoms of a serious
allergic reaction with Palonosetron Hydrochloride Injection:
o hives
o swollen
face
o breathing
trouble
o chest
pain
• Serotonin
Syndrome. A possible life-threatening problem called serotonin
syndrome can happen with medicines called 5-HT3 receptor antagonists,
including Palonosetron Hydrochloride Injection, especially when used with
medicines used to treat depression and migraine headaches called serotonin
reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors
(SNRIs), monoamine oxidase inhibitors (MAOIs) and certain other medicines. Tell
your doctor or nurse right away if you have any of the following symptoms of
serotonin syndrome:
o
agitation, seeing things that are not there (hallucinations), confusion, or
coma
o fast
heartbeat or unusual and frequent changes in your blood pressure
o
dizziness, sweating, flushing, or fever
o tremors,
stiff muscles, muscle twitching, overactive reflexes, or loss of coordination
o seizures
o nausea,
vomiting, or diarrhea
The most common side effects
of Palonosetron Hydrochloride Injection in adults are headache and
constipation.
These are not all the possible
side effects of Palonosetron Hydrochloride Injection. Call your doctor for medical
advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.
General
information about the safe and effective use of Palonosetron Hydrochloride
InjectionMedicines are sometimes prescribed for
purposes other than those listed in a Patient Information leaflet. You can ask
your doctor or pharmacist for information about Palonosetron Hydrochloride
Injection that is written for health professionals.
What
are the ingredients in Palonosetron Hydrochloride Injection?
Active
ingredient: palonosetron
hydrochloride
Inactive
ingredient: water for intravenous
administration
Rx Only
Manufactured
by: Exela Pharma Sciences LLC, Lenoir, NC 28645 USA
Distributed
by: WEST-WARD, A HIKMA COMPANY, Eatontown, NJ 07724 USA
For Product Inquiry call
1-877-845-0689.
This Patient Information has
been approved by the U.S. Food and Drug Administration.
9513-0617-00
Issued June 2017
