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ONDANSETRON 2MG/ML SOLUTION FOR INJECTION OR INFUSION

Active substance(s): ONDANSETRON HYDROCHLORIDE DIHYDRATE

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S UMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Ondansetron 2mg/ml Solution for Injection or Infusion
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains 2mg of ondansetron (as hydrochloride
dihydrate)
Each 2ml ampoule contains 4mg of ondansetron (as
hydrochloride dihydrate)
For a full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Solution for injection or infusion
Clear, colourless solution, free from particles.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Adults
Ondansetron hydrochloride is indicated for the management of
nausea and vomiting induced by cytotoxic chemotherapy and
radiotherapy, and for the prevention and treatment of postoperative nausea and vomiting (PONV).
Paediatric Population
Ondansetron hydrochloride is indicated for the management of
chemotherapy-induced nausea and vomiting (CINV) in children
aged ≥6 months, and for the prevention and treatment of PONV
in children aged ≥1 month.
4.2. Posology and method of administration
Chemotherapy and Radiotherapy
For intravenous use or for intramuscular use. Refer to Section
6.6 ‘Instructions for Use and Handling’, for information on
compatibility with intravenous fluids and other drugs.
For single use. Discard any unused product immediately
after use
Adults: The emetogenic potential of cancer treatment varies
according to the doses and combinations of chemotherapy and
radiotherapy regimens used. The route of administration and
dose of Ondansetron hydrochloride should be flexible in the
range of 8-32mg a day and selected as shown below.
Emetogenic chemotherapy and radiotherapy: Ondansetron
hydrochloride can be given either by rectal, oral (tablets or
syrup), intravenous or intramuscular administration.
For most patients receiving emetogenic chemotherapy or
radiotherapy, Ondansetron hydrochloride 8mg should be
administered as a slow intravenous or intramuscular injection
immediately before treatment, followed by 8 mg orally twelve
hourly.
To protect against delayed or prolonged emesis after the
first 24 hours, oral or rectal treatment with Ondansetron
hydrochloride should be continued for up to five days after a
course of treatment.
Highly emetogenic chemotherapy: For patients receiving highly
emetogenic chemotherapy, e.g. high-dose cisplatin, Ondansetron
hydrochloride can be given either by rectal, intravenous or
intramuscular administration.
Ondansetron hydrochloride has been shown to be equally
effective in the following dose schedules over the first 24 hours
of chemotherapy:
- A single dose of 8mg by slow intravenous or intramuscular
injection immediately before chemotherapy.
- A dose of 8mg by slow intravenous or intramuscular injection
immediately before chemotherapy, followed by two further
intravenous or intramuscular doses of 8mg two to four hours
apart, or by a constant infusion of 1mg/hour for up to 24 hours.
- A single dose of 16mg diluted in 50-l00ml of saline or other
compatible infusion fluid (see Pharmaceutical Precautions)
and infused over not less than 15 minutes immediately
before chemotherapy. A single dose greater than 16 mg
must not be given due to dose dependent increase of
QT-prolongation risk (see sections 4.4, 4.8 and 5.1).
The selection of dose regimen should be determined by the
severity of the emetogenic challenge.
The efficacy of ondansetron hydrochloride in highly emetogenic
chemotherapy may be enhanced by the addition of a single
intravenous dose of dexamethasone sodium phosphate, 20mg
administered prior to chemotherapy.
To protect against delayed or prolonged emesis after the first
24 hours, oral or rectal treatment with ondansetron
hydrochloride should be continued for up to five days
after a course of treatment.
Paediatric Population
CINV in children aged ≥6 months and adolescents
The dose for CINV can be calculated based on body surface area
(BSA) or weight – see below.
Weight-based dosing results in higher total daily doses
compared to BSA-based dosing (sections 4.4.and 5.1).
Ondansetron hydrochloride should be diluted in 5% dextrose
or 0.9% sodium chloride or other compatible infusion fluid
(see section 6.6) and infused intravenously over not less than
15 minutes.
There are no data from controlled clinical trials on the use
of ondansetron hydrochloride in the prevention of delayed or
prolonged CINV. There are no data from controlled clinical trials
on the use of ondansetron hydrochloride for radiotherapyinduced nausea and vomiting in children.
Dosing by BSA
Ondansetron hydrochloride should be administered immediately
before chemotherapy as a single intravenous dose of 5 mg/m2.
The intravenous dose must not exceed 8 mg.
Oral dosing can commence twelve hours later and may be
continued for up to 5 days (Table 1).
The total daily dose must not exceed adult dose of 32 mg.
Table 1: BSA-based dosing for Chemotherapy - Children aged
≥6 months and adolescents

Table 2: Weight-based dosing for Chemotherapy - Children aged
≥6 months and adolescents

BSA
Day 1 (a,b)
Days 2-6 (b)
≤ 10 Kg Up to 3 doses of 0.15mg/kg 2 mg syrup every
every 4 hrs
12 hrs
≥ 10 Kg Up to 3 doses of 0.15mg/kg 4 mg syrup or tablet
every 4 hrs
every 12 hrs
a The intravenous dose must not exceed 8mg.
b The total daily dose must not exceed adult dose of 32 mg.
Elderly: Ondansetron hydrochloride is well tolerated by patients
over 65 years and no alteration of dosage, dosing frequency or
route of administration are required.
Patients with Renal Impairment: No alteration of daily dosage
or frequency of dosing, or route of administration are required.
Patients with hepatic Impairment: Clearance of Ondansetron
hydrochloride is significantly reduced and serum half-life
significantly prolonged in subjects with moderate or severe
impairment of hepatic function. In such patients a total daily
dose of 8mg should not be exceeded.
Post-operative nausea and vomiting (PONV):
Adults: For the prevention of PONV ondansetron hydrochloride
can be administered orally or by intravenous or intramuscular
injection.
Ondansetron hydrochloride may be administered as a single
dose of 4mg given by intramuscular or slow intravenous
injection at induction of anaesthesia.
For treatment of established PONV a single dose of 4mg given by
intramuscular or slow intravenous injection is recommended.
Paediatric population
PONV in children aged ≥1 month and adolescents.
For prevention of PONV in paediatric patients having surgery
performed under general anaesthesia, a single dose of
ondansetron may be administered by slow intravenous
injection (not less than 30 seconds) at a dose of 0.1mg/kg up
to a maximum of 4mg either prior to, at or after induction of
anaesthesia.
For the treatment of PONV after surgery in paediatric patients
having surgery performed under general anaesthesia, a single
dose of ondansetron hydrochloride may be administered by slow
intravenous injection (not less than 30 seconds) at a dose of
0.1mg/kg up to a maximum of 4mg.
There are no data on the use of ondansetron hydrochloride in
the treatment of PONV in children below 2 years of age.
Elderly: There is limited experience in the use of ondansetron
hydrochloride in the prevention and treatment of PONV in the
elderly, however ondansetron hydrochloride is well tolerated in
patients over 65 years receiving chemotherapy.
Patients with renal impairment: No alteration of daily dosage
or frequency of dosing, or route of administration are required.
Patients with hepatic impairment: Clearance of ondansetron
hydrochloride is significantly reduced and serum half life
significantly prolonged in subjects with moderate or severe
impairment of hepatic function. In such patients a total daily
dose of 8mg should not be exceeded.
Patients with poor sparteine/debrisoquine metabolism:
The elimination half-life of ondansetron hydrochloride is not
altered in subjects classified as poor metabolisers ofsparteine
and debrisoquine. Consequently in such patients repeat dosing
will give drug exposure levels no different from those of the
general population. No alteration of daily dosage or frequency of
dosing are required.
4.3. Contraindications
Hypersensitivity to the active substance(s) or any of excipients
listed in section 6.1.
Concomitant use with apomorphine (see section 4.5).
4.4. Special warnings and precautions for use
Hypersensitivity reactions have been reported in patients
who have exhibited hypersensitivity to other selective 5HTs
receptor antagonists. Respiratory events should be treated
symptomatically and clinicians should pay particular attention to
them as precursors of hypersensitivity reactions.
Rarely, transient ECG changes including QT interval prolongation
have been reported in patients receiving ondansetron. In
addition, post-marketing cases of Torsade de Pointes have been
reported in patients using ondansetron. Ondansetron should be
administered with caution to patients who have or may develop
prolongation of QTc. These conditions include patients with
electrolyte abnormalities, with congenital long QT syndrome,
or patients taking other medicinal products that lead to QT
prolongation. Therefore, caution should be exercised in patients
with cardiac rhythm or conduction disturbances, in patients
treated with antiarrhythmic agents or betaadrenergic blocking
agents and in patients with significant electrolyte disturbances.
As ondansetron is known to increase large bowel transit time,
patients with signs of subacute intestinal obstruction should be
monitored following administration.
In patients with adenotonsillar surgery prevention of nausea and
vomiting with ondansetron may mask occult bleeding. Therefore,
such patients should be followed carefully after ondansetron.
This medicinal product contains less than 1mmol (23mg) of
sodium in each ampoule. It is essentially ‘sodium-free’.
Paediatric Population
Paediatric patients receiving ondansetron with hepatotoxic
chemotherapeutic agents should be monitored closely for
impaired hepatic function.
CINV
When calculating the dose on an mg/kg basis and administering
three doses at 4-hourly intervals, the total daily dose will be
(a,b)
(b)
BSA
Day 1
Days 2-6
higher than if one single dose of 5mg/m2 followed by an oral
dose is given. The comparative efficacy of these two different
<0.6m2 5 mg/m2 i.v. plus 2 mg syrup 2 mg syrup every
dosing regimens has not been investigated in clinical trials.
after 12 hrs
12 hrs
Cross-trial comparison indicates similar efficacy for both
≥0.6m2 5 mg/m2 i.v. plus 4 mg syrup 4 mg syrup or tablet
regimens (section 5.1).
or tablet after 12 hrs
every 12 hrs
4.5. Interaction with other medicinal products and other forms
a The intravenous dose must not exceed 8mg.
of interaction
b The total daily dose must not exceed adult dose of 32 mg
There is no evidence that ondansetron either induces or inhibits
Dosing by bodyweight
the metabolism of other drugs commonly co-administered
Weight-based dosing results in higher total daily doses
with it. Specific studies have shown that there are no
compared to BSA-based dosing (sections 4.4. and 5.1).
pharmacokinetic interactions when ondansetron is administered
Ondansetron hydrochloride should be administered immediately
with alcohol, temazepam, furosemide, alfentanil, tramadol,
before chemotherapy as a single intravenous dose of
morphine, lidocaine, thiopental or propofol.
0.15 mg/kg. The intravenous dose must not exceed 8 mg.
Ondansetron is metabolised by multiple hepatic cytochrome
Two further intravenous doses may be given in 4-hourly intervals.
P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the
The total daily dose must not exceed adult dose of 32 mg.
multiplicity of metabolic enzymes capable of metabolising
Oral dosing can commence twelve hours later and may be
ondansetron, enzyme inhibition or reduced activity of one enzyme
continued for up to 5 days (Table 2).
e.g. CYP2D6 genetic deficiency) is normally compensated by

other enzymes and should result in little or no significant change
in overall ondansetron clearance or dose requirement.
Apomorphine: Based on reports of profound hypotension and
loss of consciousness when ondansetron was administered with
apomorphine hydrochloride, concomitant use with apomorphine
is contraindicated.
Phenytoin, Carbamazepine and Rifampicin: In patients treated
with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine,
and rifampicin), the oral clearance of ondansetron was increased
and ondansetron blood concentrations were decreased.
Tramadol: Data from small studies indicate that ondansetron
may reduce the analgesic effect of tramadol.
Use of ondansetron with QT prolonging drugs may result in
additional QT prolongation.
Concomitant use of ondansetron with cardiotoxic drugs
(e.g. anthracyclines) may increase the risk of arrhythmias
(see section 4.4).
4.6. Fertility, pregnancy and lactation
Pregnancy
The safety of ondansetron for use in human pregnancy has not
been established.
Evaluation of experimental animal studies does not indicate
direct or indirect harmful effects with respect to the
development of the embryo, or foetus, the course of gestation
and pre- and postnatal development. However as animal
studies are not always predictive of human response the use of
ondansetron in pregnancy is not recommended.
Breast-feeding
Tests have shown that ondansetron passes into the milk of
lactating animals. It is therefore recommended that mothers
receiving ondansetron should not breast-feed their babies.
Fertility
There is no information on the effects of ondansetron on
human fertility.
4.7. Effects on ability to drive and use machines
In psychomotor testing ondansetron does not impair
performance nor cause sedation.
4.8. Undesirable effects
Adverse events are listed below by system organ class and
frequency. Frequencies are defined as: very common (≥1/10),
common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100),
rare (≥1/10,000 to <1/1000) and very rare (<1/10,000).
Very common, common and uncommon events were generally
determined from clinical trial data. The incidence in placebo was
taken into account. Rare and very rare events were generally
determined from post-marketing spontaneous data.
The following frequencies are estimated at the standard
recommended doses of ondansetron according to indication
and formulation.
Immune system disorders
Rare: Immediate hypersensitivity reactions,
sometimes severe including anaphylaxis.
Nervous system disorders
Very common: Headache.
Uncommon: Seizures, movement disorders (including
extrapyramidal reactions such as dystonic
reactions, oculogyric crisis and dyskinesia),
observed without definitive evidence of
persistent clinical sequelae.
Rare: Dizziness during rapid intravenous
administration.
Eye disorders
Rare: Transient visual disturbances (e.g. blurred
vision), predominantly during intravenous
administration.
Very rare: Transient blindness, predominantly during
intravenous administration.
The majority of the blindness cases reported
resolved within 20 minutes.
Most patients had received chemotherapeutic
agents, which included cisplatin.
Some cases of transient blindness were
reported as cortical in origin.
Cardiac disorders
Uncommon: Arrhythmias, chest pain with or without ST
segment depression, bradycardia.
Very rare: Transient ECG changes including QT interval
prolongation, predominantly with intravenous
administration of ondansetron.
Vascular disorders
Common:
Sensation of warmth or flushing.
Uncommon: Hypotension.
Respiratory, thoracic and mediastinal disorders
Uncommon: Hiccups.
Gastrointestinal disorders
Common:
Constipation.
Hepatobiliary disorders
Uncommon: Asymptomatic increases in liver function tests.
These events were observed commonly in
patients receiving chemotherapy with cisplatin.
General disorders and administration site conditions
Common: Local intravenous injection site reactions
(e.g. rash, urticaria, itching), sometimes
extending along the drug administration vein.
Paediatric population
The adverse event profiles in children and adolescents were
comparable to that seen in adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation
of the medicinal product is important. It allows continued
monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any
suspected adverse reactions via the Yellow Card Scheme at
www.mhra.gov.uk/yellowcard.
4.9. Overdose
Symptoms and Signs
There is limited experience of ondansetron overdose. In the
majority of cases, symptoms were similar to those already
reported in patients receiving recommended doses (see section
4.8). Manifestations that have been reported include visual
disturbances, severe constipation, hypotension and a vasovagal
episode with transient second degree AV block.
Treatment
There is no specific antidote for ondansetron, therefore in all
cases of suspected overdose, symptomatic and supportive
therapy should be given as appropriate.
The use of ipecacuanha to treat overdose with ondansetron is
not recommended, as patients are unlikely to respond due to the
anti-emetic action of ondansetron itself.

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Date

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Ondansetron may reduce the effects
of tramadol. The use of ondansetron
with medicines that affect the heart
(e.g. anthracyclines such as doxorubicin
and idarubicin) may increase the risk of
arrhythmias (changes in your heart beat).
In patients receiving cancer chemotherapy
with medicines such as doxorubicin, the
rhythm of the heart may be affected.
Caution should be taken in patients who
are being treated with medication that
suppresses abnormal rhythms of the
heart, such as beta blockers (e.g. atenolol)
or antiarrhythmics (e.g. amiodarone).
Pregnancy and Breast-feeding
If you are pregnant or breast-feeding you
should talk to your doctor or pharmacist
before taking any medicine.
Driving and using machines
Ondansetron does not affect your ability to
drive or operate machines.
3. HOW TO ADMINISTER
ONDANSETRON SOLUTION FOR
INJECTION FOR INFUSION
The injection will usually be given by a
doctor or nurse.
For patients receiving chemotherapy
or radiotherapy Ondansetron can be
given either by oral, intravenous or
intramuscular administration.
For most patients receiving chemotherapy
or radiotherapy that causes nausea and
vomiting: the recommended dose is 8 mg
given by intravenous (into a vein) or
intramuscular injection (into a muscle),
immediately before chemotherapy,
followed by 8 mg tablet after 12 hours.
For patients receiving chemotherapy
that causes severe nausea and vomiting:
any of the following dose schedules are
recommended
• 8 mg by intravenous or intramuscular
injection immediately before
chemotherapy.
• 8 mg by intravenous or intramuscular
injection immediately before
chemotherapy, followed by two further
intravenous or intramuscular doses of
8 mg 2 to 4 hours apart, or by a
constant infusion of 1mg/hour for up to
24 hours.
• 16mg of ondansetron infused over
not less than 15 minutes immediately
before chemotherapy.
After the initial ondansetron injection, you
may be given ondansetron tablets for up
to 5 days to prevent any further nausea
& vomiting.
Use in children aged over 6 months and
adolescents
The doctor will decide the dose. Look at
the label for more information.

Measure bar should be 150mm at 100% scale

Package leaflet: Information for the patient It is also used to prevent and treat
ONDANSETRON 2 mg/ml SOLUTION FOR sickness that can sometimes occur after
INJECTION OR INFUSION
an operation (adults only).
(Ondansetron)
2. W
 HAT YOU NEED TO KNOW
BEFORE ONDANSETRON SOLUTION
FOR INJECTION IS ADMINISTERED
Do not administer Ondansetron
Solution for Injection if any of the
following apply to you.
• you are allergic (hypersensitive)
to ondansetron or any of the other
ingredients of Ondansetron Solution
for Injection (please refer to Section 6
for full list of ingredients). An allergic
reaction may include rash, itching,
Read all of this leaflet carefully before
swelling of face, lips, tongue or hands/
this medicine is administered to
feet, or breathing difficulties
you because it contains important
• you are taking apomorphine (used to
information for you.
treat Parkinson’s disease).
• Keep this leaflet. You may need to
Warnings and precautions
read it again.
• If you have further questions, please Talk to your doctor or pharmacist before
ask your doctor or your pharmacist. Ondansetron Solution for Injection is
• This medicine has been prescribed administered:
• if you have symptoms of subacute
for you only. Do not pass it on to
intestinal obstruction (blockage in the
others. It may harm them, even if
bowel) such as stomach ache, nausea,
their signs of illness are the same as
vomiting, constipation or difficulty in
yours.
passing wind
• If you get any side effects, talk to
• if you have undergone tonsil surgery.
your doctor or pharmacist. This
Prevention of nausea and vomiting
includes any possible side effects not
with ondansetron may mask hidden
listed in this leaflet. See section 4.
bleeding.
In this leaflet:
Therefore, such patients should
1. What Ondansetron Solution for Injection
be monitored carefully after taking
is and what it is used for
Ondansetron.
2. What you need to know before
• if you are taking any of the following
Ondansetron Solution for Injection is
medicines: tropisetron & granisetron.
administered
• if you are having cancer chemotherapy.
3. How to administer Ondansetron
• if you have an abnormal heart rhythm,
Solution for Injection
suffer from palpitations, take drugs
4. Possible side effects
to control your heart rhythm, take
5. How to store Ondansetron Solution for
beta-blocking drugs or if you have
Injection
significant abnormalities of the
6. Contents of the pack and other
electrolytes (sodium and potassium
information
salts) in your blood.
The name of your medicine is
Please consult your doctor, even if these
Ondansetron 2mg/ml Solution for
statements were applicable to you at any
Injection or Infusion (also referred to as
time in the past.
Ondansetron injection or Ondansetron
Other medicines and Ondansetron
throughout this leaflet).
Tell your doctor or pharmacist if you are
1. WHAT ONDANSETRON SOLUTION taking, have recently taken or might have
FOR INJECTION IS AND WHAT IT
taken any other medicines.
IS USED FOR
In particular you should tell your doctor if
Ondansetron Injection contains the active you are taking any of the following:
substance Ondansetron (as Ondansetron • phenytoin, used in the treatment of
epilepsy
hydrochloride dihydrate).
• carbamazepine, used to treat epilepsy
Ondansetron belongs to the group of
and bipolar disorder
medicines known as antiemetics.
Ondansetron is used to treat nausea and • rifampicin, an antibiotic used to treat
bacterial infections.
vomiting caused by cancer chemotherapy
or radiotherapy (in adults and children).



5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
ATC code:- A04 Antiemetics and antinauseants
ATC group:- A04AAO 1 Serotonin (5HT3) antagonist
Ondansetron is a potent, highly selective 5HTs receptorantagonist. Its precise mode of action in the control of nausea
and vomiting is not known. Chemotherapeutic agents and
radiotherapy may cause release of 5HT in the small intestine
initiating a vomoting reflex by activating vagal afferents via
5HTs receptors. Ondansetron blocks the initiation of this reflex.
Activation of vagal afferents may also cause a release of 5HT in
the area postrema, located on the floor of the fourth ventricle,
and this may also promote emesis through a central mechanism.
Thus, the effect of ondansetron in the management of the
nausea and vomiting induced by cytotoxic chemotherapy and
radiotherapy is probably due to antagonism of 5HT3 receptors
on neurons located both in the peripheral and central nervous
system. The mechanisms of action in post-operative nausea and
vomiting are not known but there may be common pathways
with cytotoxic induced nausea and vomiting.
Ondansetron does not alter plasma prolactin concentrations.
The role of ondansetron in opiateinduced emesis is not yet
established.
The effect of ondansetron on the QTc interval was evaluated in
a double blind, randomised placebo and positive (moxifloxacin)
controlled, crossover study in 58 healthy adult men and
women. Ondansetron doses included 8 mg and 32 mg infused
intravenously over 15 minutes.
At the highest tested dose of 32 mg, the maximum mean
(upper limit of 90% Cl) difference in QTcF from placebo after
baseline-correction was 19.6 (21.5)msec. At the lower tested
dose of 8 mg, the maximum mean (upper limit of 90% Cl)
difference in QTcF from placebo after baseline-correction was
5.8 (7.8) msec. In this study, there were no QTcF measurements
greater than 480 msec and no QTcF prolongation was greater
than 60 msec. No significant changes were seen in the
measured electrocardiographic PR or QRS intervals.
Paediatric population
CINV
The efficacy of ondansetron in the control of emesis and nausea
induced by cancer chemotherapy was assessed in a double-blind
randomised trial in 415 patients aged 1 to 18 years (S3AB3006).
On the days of chemotherapy, patients received either
ondansetron 5 mg/m2 intravenous + ondansetron 4 mg
orally after 8-12 hrs or ondansetron 0.45 mg/kg intravenous
+ placebo orally after 8-12 hrs. Post- chemotherapy both
groups received 4 mg ondansetron syrup twice daily for 3 days.
Complete control of emesis on worst day of chemotherapy
was 49% (5 mg/m2 intravenous + ondansetron 4 mg orally)
and 41% (0.45 mg/kg intravenous + placebo orally). Postchemotherapy both groups received 4 mg ondansetron syrup
twice daily for 3 days.
A double-blind randomised placebo-controlled trial (S3AB4003)
in 438 patients aged 1 to 17 years demonstrated complete
control of emesis on worst day of chemotherapy in:
• 73% of patients when ondansetron was administered
intravenously at a dose of 5 mg/m2 intravenous together with
2-4 mg dexamethasone orally
• 71% of patients when ondansetron was administered as
syrup at a dose of 8 mg + 2-4 mg dexamethasone orally on
the days of chemotherapy.
Post-chemotherapy both groups received 4 mg ondansetron
syrup twice daily for 2 days.
The efficacy of ondansetron in 75 children aged 6 to 48 months
was investigated in an open-label, non-comparative, single-arm
study (S3A40320). All children received three 0.15 mg/kg doses
of intravenous ondansetron, administered 30 minutes before
the start of chemotherapy and then at four and eight hours
after the first dose. Complete control of emesis was achieved
in 56% of patients.
Another open-label, non-comparative, single-arm study
(S3A239) investigated the efficacy of one intravenous dose
of 0.15 mg/kg ondansetron followed by two oral ondansetron
doses of 4 mg for children aged < 12 yrs and 8 mg for children
aged ≥ 12 yrs (total no. of children n= 28). Complete control of
emesis was achieved in 42% of patients.
PONV
The efficacy of a single dose of ondansetron in the prevention
of post-operative nausea and vomiting was investigated in a
randomised, double-blind, placebo-controlled study in
670 children aged 1 to 24 months (post-conceptual age
≥44 weeks, weight ≥3 kg). Included subjects were scheduled
to undergo elective surgery under general anaesthesia
and had an ASA status ≤III. A single dose of ondansetron
0.1 mg/kg was administered within five minutes following
induction of anaesthesia. The proportion of subjects who
experienced at least one emetic episode during the 24-hour
assessment period (ITT) was greater for patients on placebo
than those receiving ondansetron ((28% vs. 11%, p <0.0001).
Four double-blind, placebo-controlled studies have been
performed in 1469 male and female patients (2 to 12 years of
age) undergoing general anaesthesia. Patients were randomised
to either single intravenous doses of ondansetron (0.1 mg/kg
for paediatric patients weighing 40 kg or less, 4 mg for
paediatric patients weighing more than 40 kg; number of
patients = 735)) or placebo (number of patients = 734). Study
drug was administered over at least 30 seconds, immediately
prior to or following anaesthesia induction. Ondansetron was
significantly more effective than placebo in preventing nausea
and vomiting. The results of these studies are summarised
in Table 3.
Table 3 Prevention and treatment of PONV in Paediatric Patients
– Treatment response over 24 hours

5.2. Pharmacokinetic properties
Following oral administration, ondansetron is passively and
completely absorbed from the gastrointestinal tract and
undergoes first pass metabolism. Peak plasma concentrations of
about 30ng/ml are attained approximately 1.5 hours after an 8mg
dose. For doses above 8mg the increase in ondansetron systemic
exposure with dose is greater than proportional; this may reflect
some reduction in first pass metabolism at higher oral doses.
Bioavailability, following oral administration, is slightly enhanced
by the presence of food but unaffected by antacids. Studies
in healthy elderly volunteers have shown slight, but clinically
insignificant, age-related increases in both oral bioavailability
(65%) and half-life (five hours) of ondansetron. Gender differences
were shown in the disposition of ondansetron, with females
having a greater rate and extent of absorption following an oral
dose and reduced systemic clearance and volume of distribution
(adjusted for weight). The disposition of ondansetron following
oral, intramuscular (IM) and intravenous (IV) dosing is similar with
a terminal half life of about three hours and steady state volume
of distribution of about 140L. Equivalent systemic exposure is
achieved after IM and IV administration of ondansetron.
A 4mg intravenous infusion of ondansetron given over five
minutes results in peak plasma concentrations of about
65ng/ml. Following intramuscular administration of ondansetron,
peak plasma concentrations of about 25ng/ml are attained
within 10 minutes of injection.
Following administration of ondansetron suppository, plasma
ondansetron concentrations become detectable between
15 and 60 minutes after dosing.
Concentrations rise in an essentially linear fashion, until peak
concentrations of 20-30ng/ml are attained, typically six hours
after dosing. Plasma concentrations then fall, but at a slower
rate than observed following oral dosing due to continued
absorption of ondansetron. The absolute bioavailability of
ondansetron from the suppository is approximately 60% and
is not affected by gender. The half life of the elimination phase
following suppository administration is determined by the
rate of ondansetron absorption, not systemic clearance and is
approximately six hours.
Females show a small, clinically insignificant, increase in halflife in comparison with males.
Ondansetron is not highly protein bound (70-76%). Ondansetron
is cleared from the systemic circulation predominantly by
hepatic metabolism through multiple enzymatic pathways.
Less than 5% of the absorbed dose is excreted unchanged
in the urine. The absence of the enzyme CYP2D6 (the
debrisoquine polymorphism) has no effect on ondansetron's
pharmacokinetics.
The pharmacokinetic properties of ondansetron are unchanged
on repeat dosing.
Special Patient Populations
Children and Adolescents (aged 1 month to 17 years)
In paediatric patients aged 1 to 4 months (n=19) undergoing
surgery, weight normalised clearance was approximately
30% slower than in patients aged 5 to 24 months (n=22) but
comparable to the patients aged 3 to 12 years. The half-life
in the patient population aged 1 to 4 month was reported to
average 6.7 hours compared to 2.9 hours for patients in the
5 to 24 month and 3 to 12 year age range. The differences
in pharmacokinetic parameters in the 1 to 4 month patient
population can be explained in part by the higher percentage of
total body water in neonates and infants and a higher volume of
distribution for water soluble drugs like ondansetron.
In paediatric patients aged 3 to 12 years undergoing elective
surgery with general anaesthesia, the absolute values for
both the clearance and volume of distribution of ondansetron
were reduced in comparison to values with adult patients.
Both parameters increased in a linear fashion with weight
and by 12 years of age, the values were approaching those
of young adults.
When clearance and volume of distribution values were
normalised by body weight, the values for these parameters
were similar between the different age group populations.
Use of weight-based dosing compensates for age-related
changes and is effective in normalising systemic exposure in
paediatric patients.
Population pharmacokinetic analysis was performed on
428 subjects (cancer patients, surgery patients and healthy
volunteers) aged 1 month to 44 years following intravenous
administration of ondansetron. Based on this analysis, systemic
exposure (AUC) of ondansetron following oral or IV dosing in
children and adolescents was comparable to adults, with the
exception of infants aged 1 to 4 months. Volume was related
to age and was lower in adults than in infants and children.
Clearance was related to weight but not to age with the
exception of infants aged 1 to 4 months. It is difficult to conclude
whether there was an additional reduction in clearance related
to age in infants 1 to 4 months or simply inherent variability
due to the low number of subjects studied in this age group.
Since patients less than 6 months of age will only receive a
single dose in PONV a decreased clearance is not likely to be
clinically relevant.
In patients with renal impairment (creatinine clearance
15-60 ml/min), both systemic clearance and volume of
distribution are reduced following IV administration of
ondansetron, resulting in a slight, but clinically insignificant,
increase in elimination half-life (5.4h). A study in patients with
severe renal impairment who required regular haemodialysis
(studied between dialyses) showed ondansetron's
pharmacokinetics to be essentially unchanged following
IV administration.
Specific studies in the elderly or patients with renal impairment
have been limited to IV and oral administration. However, it
is anticipated that the half-life of ondansetron after rectal
administration in these populations will be similar to that seen in
healthy volunteers, since the rate of elimination of ondansetron
Study
Endpoint
Ondansetron % Placebo % p value
following rectal administration is not determined by systemic
clearance.
S3A380 CR
68
39
0.001
Following oral, intravenous or intramuscular dosing in patients
S3GT09 CR
61
35
0.001
with severe hepatic impairment, ondansetron's systemic
clearance is markedly reduced with prolonged elimination
S3A381 CR
53
17
0.001
half-lives (15-32 h) and an oral bioavailability approaching
S3GT11 no nausea 64
51
0.004
100% due to reduced pre-systemic metabolism.
S3GT11 no emesis 60
47
0.004
The pharmacokinetics of ondansetron following administration
as a suppository have not been evaluated in patients with
CR = no emetic episodes, rescue or withdrawal
hepatic impairment.

106938/2

5.3. Preclinical safety data
No additional data of relevance.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Citric acid monhydrate
Sodium citrate
Sodium chloride
Water for injections.
6.2. Incompatibilities
Ondansetron injection should not be administered in the same
syringe or infusion as any other medication.
6.3. Shelf life
36 months (unopened).
After dilution, see section 6.4 Special precautions for storage.
6.4. Special precautions for storage
Do not store above 25°C.
Keep the ampoule in the outer carton
Keep out of the reach and sight of children
After dilution:Chemical and physical in use stability has been demonstrated
for 24 hours at 25°C and 5°C.
From a microbiological point of view, the product should be used
immediately. If not used immediately, in-use storage times and
conditions prior to use are the responsibility of the user and
would not normally be longer than 24 hours at 2-8°C, unless
opening and dilution has taken place in controlled and validated
aseptic conditions.
6.5. Nature and contents of container
Type I Ph Eur amber glass 3ml capacity ampoules. Each pack
contains one, five or ten ampoules.
6.6. Special precautions for disposal
For single use. Discard any unused product immediately
after use.
Ondansetron injection should not be autoclaved.
Compatibility with intravenous fluids:
Ondansetron injection should only be admixed with those
infusion solutions which are recommendedSodium Chloride Intravenous Infusion BP 0.9%w/v
Glucose Intravenous Infusion BP 5%w/v
Mannitol Intravenous Infusion BP 10%w/v
Ringers Intravenous Infusion
Potassium Chloride 0.3%w/v and Sodium Chloride 0.9%w/v
Intravenous Infusion BP
Potassium Chloride 0.3%w/v and Glucose 5%w/v Intravenous
Infusion BP
In keeping with good pharmaceutical practice dilutions of
Ondansetron Injection in intravenous fluids should be prepared
at the time of infusion although chemical and physical in use
stability after dilution has been demonstrated for 24 hours at
25°C and 5°C.
Compatibility with other drugs: Ondansetron may be
administered by intravenous infusion at 1mg/hour, e.g. from
an infusion bag or syringe pump. The following drugs may be
administered via the Y-site of the ondansetron giving set for
ondansetron concentrations of 16 to 160 micrograms/ml
(e.g. 8 mg/500 ml and 8 mg/50 ml respectively):
Cisplatin: Concentrations up to 0.48 mg/ml (e.g. 240 mg in
500 ml) administered over one to eight hours.
5 -Fluorouracil: Concentrations up to 0.8 mg/ml (e.g. 2.4g in
3 litres or 400mg in 500ml) administered at a rate of at least
20ml per hour (500 ml per 24 hours). Higher concentrations
of 5-fluorouracil may cause precipitation of ondansetron.
The 5-fluorouracil infusion may contain up to 0.045%w/v
magnesium chloride in addition to other excipients shown to
be compatible.
Carboplatin: Concentrations in the range 0.18mg/ml to
9.9mg/ml (e.g. 90mg in 500ml to 990mg in 100ml),
administered over ten minutes to one hour.
Etoposide: Concentrations in the range 0.14 mg/ml to
0.25 mg/ml (e.g. 72mg in 500ml to 250 mg in 1 litre),
administered over thirty minutes to one hour.
Ceftazidime: Doses in the range 250 mg to 2000 mg
reconstituted with Water for Injections BP as recommended
by the manufacturer (e.g. 2.5ml for 250mg and 10ml for 2g
ceftazidime) and given as an intravenous bolus injection over
approximately five minutes.
Cyclophosphamide: Doses in the range 100mg to 1g,
reconstituted with Water for Injections BP, 5ml per 100mg
cyclophosphamide, as recommended by the manufacturer and
given as an intravenous bolus injection over approximately
five minutes.
Doxorubicin: Doses in the range 10-100mg reconstituted
with Water for Injections BP, 5ml per 10mg doxorubicin, as
recommended by the manufacturer and given as an intravenous
bolus injection over approximately five minutes.
Dexamethasone: Dexamethasone sodium phosphate 20mg may
be administered as a slow intravenous injection over two to five
minutes via the Y-site of an infusion set delivering 8 or 16mg
of ondansetron diluted in 50-100ml of a compatible infusion
fluid over approximately 15 minutes. Compatibility between
dexamethasone sodium phosphate and ondansetron has been
demonstrated supporting administration of these drugs through
the same giving set resulting in concentrations in line of
32 micrograms to 2.5mg/ml for dexamethasone sodium
phosphate and |8 micrograms to 1mg/ml for ondansetron.
7. MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd
Ash Road North
Wrexham
LL13 9UF
U.K
8. MARKETING AUTHORISATION NUMBER(S)
PL 29831/0154
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Renewed: 06/11/2013
10. DATE OF REVISION OF THE TEXT
03/2016

106938/2

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Date

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Ondensetron injection common leaflet UK
Description

• The other ingredients are sodium
chloride, sodium citrate, citric acid
monohydrate and water for injections
• This medicinal product contains less than
1 mmol sodium (23mg) per ampoule, i.e.
essentially 'sodium-free'.
What Ondansetron solution for injection
or infusion looks like and contents of
the pack
Ondansetron 2mg/ml Solution for Injection
or Infusion is a clear colourless solution.
Ondansetron Injection is available in 1, 5, or
10, ampoules at 2 ml or 1, 5, or 10, at 4 ml.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Wockhardt UK Limited, Ash Road North,
Wrexham, LL13 9UF, United Kingdom.
Manufacturer
CP Pharmaceuticals Limited,
Ash Road North, Wrexham, L13 9UF,
United Kingdom.
Other formats:
To listen to or request a copy of this leaflet
in Braille, large print or audio please call,
free of charge:
0800 198 5000 (UK Only)
Please be ready to give the following
information:
Product name
Reference
number
Ondansetron 2mg/ml PL 29831/0153
Solution for Injection PL 29831/0154
or Infusion
This is a service provided by the Royal
National Institute of Blind People.
This leaflet was last revised in 04/2016

Wockhardt UK Limited

44

Text free area (non-printing)

Keyline (non-printing)

Process Black

Colours Used

• Each ampoule contains either 4mg or
8mg Ondansetron (as Ondansetron
hydrochloride dihydrate)

Customer

Other possible side effects are:
• Headache
• Feeling of warmth in the head or
stomach
• Dizziness or lightheaded feeling
• Slow or irregular heartbeat
• Chest pain
• Flushes of the face
• Hiccups
• Upset bowels - constipation
• Irritation and redness at the site of
injection
If you have any blood tests to check how
your liver is working, this medicine may
affect the results. If you feel unwell or
have any other unusual discomfort you do
not understand, tell your doctor as soon
as possible.
Reporting of side effects
If you get any side effects, talk to your
doctor, pharmacist or nurse. This includes
any possible side effects not listed in this
leaflet. You can also report side effects
directly via the Yellow Card Scheme at
www.mhra.gov.uk/yellowcard.
By reporting side effects you can help
provide more information on the safety of
this medicine.
5. H
 OW TO STORE ONDANSETRON
SOLUTION FOR INJECTION OR
INFUSION
Keep this medicine out of the sight and
reach of children.
Do not store above 25°C.
Keep the ampoule in the outer carton.
Do not use Ondansetron Solution for
Injection or Infusion after the expiry date
which is stated on the carton. The expiry
date refers to the last day of that month.
Chemical and physical in use stability
has been demonstrated for 24 hours at
25°C and 5°C. From a microbiological
point of view, the product should be used
immediately. If not used immediately,
in-use storage times and conditions prior
to use are the responsibility of the user
and would not normally be longer than
24 hours at 2-8°C, unless opening and
dilution has taken place in controlled and
validated aseptic conditions.
For single use. Discard any unused
product immediately after use.
Do not use if the ampoule is damaged or if
the solution is cloudy or contains particles.
6. C ONTENTS OF THE PACK AND
OTHER INFORMATION
What Ondansetron solution for injection
or infusion contains
• The active substance is Ondansetron
(as Ondansetron hydrochloride dihydrate).

Measure bar should be 150mm at 100% scale

On the day of chemotherapy or radiotherapy
• the first dose is given by an injection into
a vein, just before your child's treatment.
After chemotherapy, your child's
medicine will usually be given by mouth;
the usual dose is a 4mg ondansetron
tablet or 4mg ondansetron syrup twelve
hours later.
On the following days
• one 4mg tablet or 4mg syrup twice a
day.
• this can be given for up to five days.
To prevent nausea and vomiting after an
operation: the usual adult dose is 4 mg
given by intravenous or intramuscular
injection before the operation.
For children aged over 1 month and
adolescents, the doctor will decide the
dose. The maximum dose is 4mg given
as an injection into the vein. This will be
given just before the operation.
To treat nausea and vomiting after an
operation: the usual adult dose is 4 mg
given as intravenous or intramuscular
injection.
For children aged over 1 month and
adolescents, the doctor will decide the
dose. The maximum dose is 4mg given as
an injection into the vein.
Patients with moderate or severe liver
disease: the total daily dose should not be
more than 8 mg.
If you think you may have missed a dose
or had too much, let your doctor or nurse
know immediately.
4. POSSIBLE SIDE EFFECTS
Like all medicines, Ondansetron can have
side effects, although not everybody gets
them.
A few people can be allergic to some
medicines; if any of the following rare side
effects come on soon after having your
injection, tell your doctor immediately:
• Sudden chest tightness or wheezing
• Swelling of eyelids, face or lips
• Skin rash - red spots or hives
(skin lumps)
• Collapse
The following side effects are very rare
but if you have them you should let your
doctor know immediately:
• Upward rolling of the eyes
• Abnormal muscular stiffness, body
movements or shaking
• Fits
• Blurring of vision
• Temporary blindness
• Yellowing of the skin or whites of the
eyes caused by liver problems
• Low blood pressure (symptoms may
include dizziness, fainting and nausea)

Package leaflet: Information for the patient
ONDANSETRON 2 mg/ml SOLUTION FOR INJECTION OR INFUSION
(Ondansetron)


FPO

Read all of this leaflet carefully before this medicine is
administered to you because it contains important
information for you.
• Keep this leaflet. You may need to read it again.
• If you have further questions, please ask your doctor
or your pharmacist.
• This medicine has been prescribed for you only.
Do not pass it on to others. It may harm them, even if
their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or
pharmacist. This includes any possible side effects not
listed in this leaflet. See section 4.
In this leaflet:
1. What Ondansetron Solution for Injection is and what it is
used for
2. What you need to know before Ondansetron Solution for
Injection is administered
3. How to administer Ondansetron Solution for Injection
4. Possible side effects
5. How to store Ondansetron Solution for Injection
6. Contents of the pack and other information
The name of your medicine is Ondansetron 2mg/ml Solution for
Injection or Infusion (also referred to as Ondansetron injection
or Ondansetron throughout this leaflet).
1. WHAT ONDANSETRON SOLUTION FOR INJECTION IS
AND WHAT IT IS USED FOR
Ondansetron Injection contains the active substance
Ondansetron (as Ondansetron hydrochloride dihydrate).



Ondansetron belongs to the group of medicines known as
antiemetics.
Ondansetron is used to treat nausea and vomiting caused by
cancer chemotherapy or radiotherapy (in adults and children).
It is also used to prevent and treat sickness that can
sometimes occur after an operation (adults only).
2. WHAT YOU NEED TO KNOW BEFORE ONDANSETRON
SOLUTION FOR INJECTION IS ADMINISTERED
Do not administer Ondansetron Solution for Injection if
any of the following apply to you.
• you are allergic (hypersensitive) to ondansetron or any of
the other ingredients of Ondansetron Solution for Injection
(please refer to Section 6 for full list of ingredients).
An allergic reaction may include rash, itching, swelling of
face, lips, tongue or hands/feet, or breathing difficulties
• you are taking apomorphine (used to treat Parkinson’s
disease).
Warnings and precautions
Talk to your doctor or pharmacist before Ondansetron Solution
for Injection is administered:
• if you have symptoms of subacute intestinal obstruction
(blockage in the bowel) such as stomach ache, nausea,
vomiting, constipation or difficulty in passing wind
• if you have undergone tonsil surgery. Prevention of nausea
and vomiting with ondansetron may mask hidden bleeding.
Therefore, such patients should be monitored carefully
after taking Ondansetron.
• if you are taking any of the following medicines: tropisetron
& granisetron.
• if you are having cancer chemotherapy.
• if you have an abnormal heart rhythm, suffer from
palpitations, take drugs to control your heart rhythm, take
beta-blocking drugs or if you have significant abnormalities of
the electrolytes (sodium and potassium salts) in your blood.
Please consult your doctor, even if these statements were
applicable to you at any time in the past.
Other medicines and Ondansetron
Tell your doctor or pharmacist if you are taking, have recently
taken or might have taken any other medicines.
In particular you should tell your doctor if you are taking any
of the following:
• phenytoin, used in the treatment of epilepsy
• carbamazepine, used to treat epilepsy and bipolar disorder


SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Ondansetron 2mg/ml Solution for Injection or Infusion
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains 2mg of ondansetron (as hydrochloride dihydrate)
Each 2ml ampoule contains 4mg of ondansetron (as hydrochloride dihydrate)
For a full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Solution for injection or infusion
Clear, colourless solution, free from particles.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Adults
Ondansetron hydrochloride is indicated for the management of nausea and vomiting induced by
cytotoxic chemotherapy and radiotherapy, and for the prevention and treatment of post-operative
nausea and vomiting (PONV).
Paediatric Population
Ondansetron hydrochloride is indicated for the management of chemotherapy-induced nausea
and vomiting (CINV) in children aged ≥6 months, and for the prevention and treatment of PONV in
children aged ≥1 month.
4.2. Posology and method of administration

Chemotherapy and Radiotherapy
For intravenous use or for intramuscular use. Refer to Section 6.6 ‘Instructions for Use and
Handling’, for information on compatibility with intravenous fluids and other drugs.
For single use. Discard any unused product immediately after use
Adults: The emetogenic potential of cancer treatment varies according to the doses and
combinations of chemotherapy and radiotherapy regimens used. The route of administration and
dose of Ondansetron hydrochloride should be flexible in the range of 8-32mg a day and selected
as shown below.
Emetogenic chemotherapy and radiotherapy: Ondansetron hydrochloride can be given either by
rectal, oral (tablets or syrup), intravenous or intramuscular administration.
For most patients receiving emetogenic chemotherapy or radiotherapy, Ondansetron
hydrochloride 8mg should be administered as a slow intravenous or intramuscular injection
immediately before treatment, followed by 8 mg orally twelve hourly.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with
Ondansetron hydrochloride should be continued for up to five days after a course of treatment.
Highly emetogenic chemotherapy: For patients receiving highly emetogenic chemotherapy,
e.g. high-dose cisplatin, Ondansetron hydrochloride can be given either by rectal, intravenous or
intramuscular administration.
Ondansetron hydrochloride has been shown to be equally effective in the following dose
schedules over the first 24 hours of chemotherapy:
- A single dose of 8mg by slow intravenous or intramuscular injection immediately before
chemotherapy.
- A dose of 8mg by slow intravenous or intramuscular injection immediately before chemotherapy,
followed by two further intravenous or intramuscular doses of 8mg two to four hours apart,
or by a constant infusion of 1mg/hour for up to 24 hours.
- A single dose of 16mg diluted in 50-l00ml of saline or other compatible infusion fluid
(see Pharmaceutical Precautions) and infused over not less than 15 minutes immediately before
chemotherapy. A single dose greater than 16 mg must not be given due to dose dependent
increase of QT-prolongation risk (see sections 4.4, 4.8 and 5.1).
The selection of dose regimen should be determined by the severity of the emetogenic challenge.
The efficacy of ondansetron hydrochloride in highly emetogenic chemotherapy may be enhanced
by the addition of a single intravenous dose of dexamethasone sodium phosphate, 20mg
administered prior to chemotherapy.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with
ondansetron hydrochloride should be continued for up to five days after a course of treatment.
Paediatric Population
CINV in children aged ≥6 months and adolescents
The dose for CINV can be calculated based on body surface area (BSA) or weight – see below.
Weight-based dosing results in higher total daily doses compared to BSA-based dosing
(sections 4.4.and 5.1).
Ondansetron hydrochloride should be diluted in 5% dextrose or 0.9% sodium chloride or other
compatible infusion fluid (see section 6.6) and infused intravenously over not less than 15 minutes.
There are no data from controlled clinical trials on the use of ondansetron hydrochloride in the
prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the
use of ondansetron hydrochloride for radiotherapy-induced nausea and vomiting in children.
Dosing by BSA
Ondansetron hydrochloride should be administered immediately before chemotherapy as a single
intravenous dose of 5 mg/m2. The intravenous dose must not exceed 8 mg.
Oral dosing can commence twelve hours later and may be continued for up to 5 days (Table 1).
The total daily dose must not exceed adult dose of 32 mg.
Table 1: BSA-based dosing for Chemotherapy - Children aged ≥6 months and adolescents
BSA
<0.6m2

Day 1 (a,b)
Days 2-6 (b)
5 mg/m2 i.v. plus 2 mg syrup
2 mg syrup every 12 hrs
after 12 hrs
≥0.6m2
5 mg/m2 i.v. plus 4 mg syrup
4 mg syrup or tablet every
or tablet after 12 hrs
12 hrs
a The intravenous dose must not exceed 8mg.
b The total daily dose must not exceed adult dose of 32 mg
Dosing by bodyweight
Weight-based dosing results in higher total daily doses compared to BSA-based dosing
(sections 4.4. and 5.1).
Ondansetron hydrochloride should be administered immediately before chemotherapy as a single
intravenous dose of 0.15 mg/kg. The intravenous dose must not exceed 8 mg.
Two further intravenous doses may be given in 4-hourly intervals. The total daily dose must not
exceed adult dose of 32 mg.
Oral dosing can commence twelve hours later and may be continued for up to 5 days (Table 2).
Table 2: Weight-based dosing for Chemotherapy - Children aged ≥6 months and adolescents
BSA
≤ 10 Kg

Day 1 (a,b)
Days 2-6 (b)
Up to 3 doses of 0.15mg/kg
2 mg syrup every 12 hrs
every 4 hrs
≥ 10 Kg
Up to 3 doses of 0.15mg/kg
4 mg syrup or tablet every
every 4 hrs
12 hrs
a The intravenous dose must not exceed 8mg.
b The total daily dose must not exceed adult dose of 32 mg.
Elderly: Ondansetron hydrochloride is well tolerated by patients over 65 years and no alteration
of dosage, dosing frequency or route of administration are required.
Patients with Renal Impairment: No alteration of daily dosage or frequency of dosing, or route
of administration are required.
Patients with hepatic Impairment: Clearance of Ondansetron hydrochloride is significantly
reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment
of hepatic function. In such patients a total daily dose of 8mg should not be exceeded.
Post-operative nausea and vomiting (PONV):
Adults: For the prevention of PONV ondansetron hydrochloride can be administered orally or by
intravenous or intramuscular injection.
Ondansetron hydrochloride may be administered as a single dose of 4mg given by intramuscular
or slow intravenous injection at induction of anaesthesia.
For treatment of established PONV a single dose of 4mg given by intramuscular or slow
intravenous injection is recommended.
Paediatric population
PONV in children aged ≥1 month and adolescents.
For prevention of PONV in paediatric patients having surgery performed under general
anaesthesia, a single dose of ondansetron may be administered by slow intravenous injection
(not less than 30 seconds) at a dose of 0.1mg/kg up to a maximum of 4mg either prior to,
at or after induction of anaesthesia.
For the treatment of PONV after surgery in paediatric patients having surgery performed under
general anaesthesia, a single dose of ondansetron hydrochloride may be administered by slow
intravenous injection (not less than 30 seconds) at a dose of 0.1mg/kg up to a maximum of 4mg.
There are no data on the use of ondansetron hydrochloride in the treatment of PONV in children
below 2 years of age.

• rifampicin, an antibiotic used to treat bacterial infections.
Ondansetron may reduce the effects of tramadol.
The use of ondansetron with medicines that affect the heart
(e.g. anthracyclines such as doxorubicin and idarubicin) may
increase the risk of arrhythmias (changes in your heart beat).
In patients receiving cancer chemotherapy with medicines
such as doxorubicin, the rhythm of the heart may be affected.
Caution should be taken in patients who are being treated
with medication that suppresses abnormal rhythms of the
heart, such as beta blockers (e.g. atenolol) or antiarrhythmics
(e.g. amiodarone).
Pregnancy and Breast-feeding
If you are pregnant or breast-feeding you should talk to your
doctor or pharmacist before taking any medicine.
Driving and using machines
Ondansetron does not affect your ability to drive or operate
machines.
3. HOW TO ADMINISTER ONDANSETRON SOLUTION
FOR INJECTION FOR INFUSION
The injection will usually be given by a doctor or nurse.
For patients receiving chemotherapy or radiotherapy
Ondansetron can be given either by oral, intravenous or
intramuscular administration.
For most patients receiving chemotherapy or radiotherapy that
causes nausea and vomiting: the recommended dose is 8 mg
given by intravenous (into a vein) or intramuscular injection
(into a muscle), immediately before chemotherapy, followed by
8 mg tablet after 12 hours.
For patients receiving chemotherapy that causes severe
nausea and vomiting:
any of the following dose schedules are recommended
• 8 mg by intravenous or intramuscular injection immediately
before chemotherapy.
• 8 mg by intravenous or intramuscular injection immediately
before chemotherapy, followed by two further intravenous
or intramuscular doses of 8 mg 2 to 4 hours apart, or by
a constant infusion of 1mg/hour for up to 24 hours.
• 16mg of ondansetron infused over not less than
15 minutes immediately before chemotherapy. After the
initial ondansetron injection, you may be given ondansetron
tablets for up to 5 days to prevent any further nausea
& vomiting.

Elderly: There is limited experience in the use of ondansetron hydrochloride in the prevention and
treatment of PONV in the elderly, however ondansetron hydrochloride is well tolerated in patients
over 65 years receiving chemotherapy.
Patients with renal impairment: No alteration of daily dosage or frequency of dosing, or route of
administration are required.
Patients with hepatic impairment: Clearance of ondansetron hydrochloride is significantly
reduced and serum half life significantly prolonged in subjects with moderate or severe impairment
of hepatic function. In such patients a total daily dose of 8mg should not be exceeded.
Patients with poor sparteine/debrisoquine metabolism: The elimination half-life of
ondansetron hydrochloride is not altered in subjects classified as poor metabolisers ofsparteine
and debrisoquine. Consequently in such patients repeat dosing will give drug exposure levels
no different from those of the general population. No alteration of daily dosage or frequency of
dosing are required.
4.3. Contraindications
Hypersensitivity to the active substance(s) or any of excipients listed in section 6.1.
Concomitant use with apomorphine (see section 4.5).
4.4. Special warnings and precautions for use
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to
other selective 5HTs receptor antagonists. Respiratory events should be treated symptomatically
and clinicians should pay particular attention to them as precursors of hypersensitivity reactions.
Rarely, transient ECG changes including QT interval prolongation have been reported in patients
receiving ondansetron. In addition, post-marketing cases of Torsade de Pointes have been
reported in patients using ondansetron. Ondansetron should be administered with caution to
patients who have or may develop prolongation of QTc. These conditions include patients with
electrolyte abnormalities, with congenital long QT syndrome, or patients taking other medicinal
products that lead to QT prolongation. Therefore, caution should be exercised in patients with
cardiac rhythm or conduction disturbances, in patients treated with antiarrhythmic agents or
betaadrenergic blocking agents and in patients with significant electrolyte disturbances.
As ondansetron is known to increase large bowel transit time, patients with signs of subacute
intestinal obstruction should be monitored following administration.
In patients with adenotonsillar surgery prevention of nausea and vomiting with ondansetron may
mask occult bleeding. Therefore, such patients should be followed carefully after ondansetron.
This medicinal product contains less than 1mmol (23mg) of sodium in each ampoule. It is
essentially ‘sodium-free’.
Paediatric Population
Paediatric patients receiving ondansetron with hepatotoxic chemotherapeutic agents should be
monitored closely for impaired hepatic function.
CINV
When calculating the dose on an mg/kg basis and administering three doses at 4-hourly intervals,
the total daily dose will be higher than if one single dose of 5mg/m2 followed by an oral dose is
given. The comparative efficacy of these two different dosing regimens has not been investigated
in clinical trials. Cross-trial comparison indicates similar efficacy for both regimens (section 5.1).
4.5. Interaction with other medicinal products and other forms of interaction
There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs
commonly co-administered with it. Specific studies have shown that there are no pharmacokinetic
interactions when ondansetron is administered with alcohol, temazepam, furosemide, alfentanil,
tramadol, morphine, lidocaine, thiopental or propofol.
Ondansetron is metabolised by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6
and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising ondansetron,
enzyme inhibition or reduced activity of one enzyme e.g. CYP2D6 genetic deficiency) is normally
compensated by other enzymes and should result in little or no significant change in overall
ondansetron clearance or dose requirement.
Apomorphine: Based on reports of profound hypotension and loss of consciousness when
ondansetron was administered with apomorphine hydrochloride, concomitant use with
apomorphine is contraindicated.
Phenytoin, Carbamazepine and Rifampicin: In patients treated with potent inducers of CYP3A4
(i.e. phenytoin, carbamazepine, and rifampicin), the oral clearance of ondansetron was increased
and ondansetron blood concentrations were decreased.
Tramadol: Data from small studies indicate that ondansetron may reduce the analgesic effect of
tramadol.
Use of ondansetron with QT prolonging drugs may result in additional QT prolongation.
Concomitant use of ondansetron with cardiotoxic drugs (e.g. anthracyclines) may increase the
risk of arrhythmias (see section 4.4).
4.6. Fertility, pregnancy and lactation
Pregnancy
The safety of ondansetron for use in human pregnancy has not been established.
Evaluation of experimental animal studies does not indicate direct or indirect harmful effects
with respect to the development of the embryo, or foetus, the course of gestation and pre- and
postnatal development. However as animal studies are not always predictive of human response
the use of ondansetron in pregnancy is not recommended.
Breast-feeding
Tests have shown that ondansetron passes into the milk of lactating animals. It is therefore
recommended that mothers receiving ondansetron should not breast-feed their babies.
Fertility
There is no information on the effects of ondansetron on human fertility.
4.7. Effects on ability to drive and use machines
In psychomotor testing ondansetron does not impair performance nor cause sedation.
4.8. Undesirable effects
Adverse events are listed below by system organ class and frequency. Frequencies are defined
as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100),
rare (≥1/10,000 to <1/1000) and very rare (<1/10,000). Very common, common and uncommon
events were generally determined from clinical trial data. The incidence in placebo was taken into
account. Rare and very rare events were generally determined from post-marketing spontaneous
data.
The following frequencies are estimated at the standard recommended doses of ondansetron
according to indication and formulation.
Immune system disorders
Rare:
Immediate hypersensitivity reactions, sometimes severe including anaphylaxis.
Nervous system disorders
Very common: Headache.
Uncommon: Seizures, movement disorders (including extrapyramidal reactions such as
dystonic reactions, oculogyric crisis and dyskinesia), observed without definitive
evidence of persistent clinical sequelae.
Rare:
Dizziness during rapid intravenous administration.
Eye disorders
Rare: Transient visual disturbances (e.g. blurred vision), predominantly during
intravenous administration.
Very rare: Transient blindness, predominantly during intravenous administration. The
majority of the blindness cases reported resolved within 20 minutes. Most
patients had received chemotherapeutic agents, which included cisplatin.
Some cases of transient blindness were reported as cortical in origin.
Cardiac disorders
Uncommon: Arrhythmias, chest pain with or without ST segment depression, bradycardia.
Very rare: Transient ECG changes including QT interval prolongation, predominantly with
intravenous administration of ondansetron.
Vascular disorders
Common:
Sensation of warmth or flushing.
Uncommon: Hypotension.
Respiratory, thoracic and mediastinal disorders
Uncommon: Hiccups.
Gastrointestinal disorders
Common:
Constipation.
Hepatobiliary disorders
Uncommon: Asymptomatic increases in liver function tests. These events were observed
commonly in patients receiving chemotherapy with cisplatin.
General disorders and administration site conditions
Common: Local intravenous injection site reactions (e.g. rash, urticaria, itching), sometimes
extending along the drug administration vein.
Paediatric population
The adverse event profiles in children and adolescents were comparable to that seen in adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at
www.mhra.gov.uk/yellowcard.

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Use in children aged over 6 months and adolescents
The doctor will decide the dose. Look at the label for more
information.
On the day of chemotherapy or radiotherapy
• the first dose is given by an injection into a vein, just before
your child's treatment. After chemotherapy, your child's
medicine will usually be given by mouth; the usual dose
is a 4mg ondansetron tablet or 4mg ondansetron syrup
twelve hours later.
On the following days
• one 4mg tablet or 4mg syrup twice a day.
• this can be given for up to five days.
To prevent nausea and vomiting after an operation: the usual
adult dose is 4 mg given by intravenous or intramuscular
injection before the operation.
For children aged over 1 month and adolescents, the doctor
will decide the dose. The maximum dose is 4mg given as
an injection into the vein. This will be given just before the
operation.
To treat nausea and vomiting after an operation: the usual
adult dose is 4 mg given as intravenous or intramuscular
injection.
For children aged over 1 month and adolescents, the doctor
will decide the dose. The maximum dose is 4mg given as an
injection into the vein.
Patients with moderate or severe liver disease: the total daily
dose should not be more than 8 mg.
If you think you may have missed a dose or had too much, let
your doctor or nurse know immediately.

• Temporary blindness
• Yellowing of the skin or whites of the eyes caused by liver
problems
• Low blood pressure (symptoms may include dizziness,
fainting and nausea)
Other possible side effects are:
• Headache
• Feeling of warmth in the head or stomach
• Dizziness or lightheaded feeling
• Slow or irregular heartbeat
• Chest pain
• Flushes of the face
• Hiccups
• Upset bowels - constipation
• Irritation and redness at the site of injection
If you have any blood tests to check how your liver is working,
this medicine may affect the results. If you feel unwell or have
any other unusual discomfort you do not understand, tell your
doctor as soon as possible.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or
nurse. This includes any possible side effects not listed in this
leaflet. You can also report side effects directly via the Yellow
Card Scheme at www.mhra.gov.uk/yellowcard.
By reporting side effects you can help provide more
information on the safety of this medicine.
5. HOW TO STORE ONDANSETRON SOLUTION FOR
INJECTION OR INFUSION
Keep this medicine out of the sight and reach of children.
Do not store above 25°C.
Keep the ampoule in the outer carton.
Do not use Ondansetron Solution for Injection or Infusion after
the expiry date which is stated on the carton. The expiry date
refers to the last day of that month.
Chemical and physical in use stability has been demonstrated
for 24 hours at 25°C and 5°C. From a microbiological point
of view, the product should be used immediately. If not used
immediately, in-use storage times and conditions prior to use
are the responsibility of the user and would not normally be
longer than 24 hours at 2-8°C, unless opening and dilution
has taken place in controlled and validated aseptic conditions.
For single use. Discard any unused product immediately
after use.
Do not use if the ampoule is damaged or if the solution is
cloudy or contains particles.

4. POSSIBLE SIDE EFFECTS
Like all medicines, Ondansetron can have side effects,
although not everybody gets them.
A few people can be allergic to some medicines; if any of the
following rare side effects come on soon after having your
injection, tell your doctor immediately:
• Sudden chest tightness or wheezing
• Swelling of eyelids, face or lips
• Skin rash - red spots or hives (skin lumps)
• Collapse
The following side effects are very rare but if you have them
you should let your doctor know immediately:
• Upward rolling of the eyes
• Abnormal muscular stiffness, body movements or shaking
• Fits
• Blurring of vision



4.9. Overdose
Symptoms and Signs
There is limited experience of ondansetron overdose. In the majority of cases, symptoms were
similar to those already reported in patients receiving recommended doses (see section 4.8).
Manifestations that have been reported include visual disturbances, severe constipation,
hypotension and a vasovagal episode with transient second degree AV block.
Treatment
There is no specific antidote for ondansetron, therefore in all cases of suspected overdose,
symptomatic and supportive therapy should be given as appropriate.
The use of ipecacuanha to treat overdose with ondansetron is not recommended, as patients are
unlikely to respond due to the anti-emetic action of ondansetron itself.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
ATC code:- A04 Antiemetics and antinauseants
ATC group:- A04AAO 1 Serotonin (5HT3) antagonist
Ondansetron is a potent, highly selective 5HTs receptor-antagonist. Its precise mode of action in
the control of nausea and vomiting is not known. Chemotherapeutic agents and radiotherapy may
cause release of 5HT in the small intestine initiating a vomoting reflex by activating vagal afferents
via 5HTs receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents
may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle,
and this may also promote emesis through a central mechanism. Thus, the effect of ondansetron in
the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy
is probably due to antagonism of 5HT3 receptors on neurons located both in the peripheral and
central nervous system. The mechanisms of action in post-operative nausea and vomiting are not
known but there may be common pathways with cytotoxic induced nausea and vomiting.
Ondansetron does not alter plasma prolactin concentrations. The role of ondansetron in
opiateinduced emesis is not yet established.
The effect of ondansetron on the QTc interval was evaluated in a double blind, randomised
placebo and positive (moxifloxacin) controlled, crossover study in 58 healthy adult men and
women. Ondansetron doses included 8 mg and 32 mg infused intravenously over 15 minutes.
At the highest tested dose of 32 mg, the maximum mean (upper limit of 90% Cl) difference in
QTcF from placebo after baseline-correction was 19.6 (21.5)msec. At the lower tested dose
of 8 mg, the maximum mean (upper limit of 90% Cl)difference in QTcF from placebo after
baseline-correction was 5.8 (7.8) msec. In this study, there were no QTcF measurements greater
than 480 msec and no QTcF prolongation was greater than 60 msec. No significant changes were
seen in the measured electrocardiographic PR or QRS intervals.
Paediatric population
CINV
The efficacy of ondansetron in the control of emesis and nausea induced by cancer chemotherapy
was assessed in a double-blind randomised trial in 415 patients aged 1 to 18 years (S3AB3006).
On the days of chemotherapy, patients received either ondansetron 5 mg/m2 intravenous +
ondansetron 4 mg orally after 8-12 hrs or ondansetron 0.45 mg/kg intravenous + placebo orally
after 8-12 hrs. Post- chemotherapy both groups received 4 mg ondansetron syrup twice daily for
3 days. Complete control of emesis on worst day of chemotherapy was 49% (5 mg/m2 intravenous
+ ondansetron 4 mg orally) and 41% (0.45 mg/kg intravenous + placebo orally). Post-chemotherapy
both groups received 4 mg ondansetron syrup twice daily for 3 days.
A double-blind randomised placebo-controlled trial (S3AB4003) in 438 patients aged 1 to 17 years
demonstrated complete control of emesis on worst day of chemotherapy in:
• 73% of patients when ondansetron was administered intravenously at a dose of 5 mg/m2
intravenous together with 2-4 mg dexamethasone orally
• 71% of patients when ondansetron was administered as syrup at a dose of 8 mg + 2-4 mg
dexamethasone orally on the days of chemotherapy.
Post-chemotherapy both groups received 4 mg ondansetron syrup twice daily for 2 days.
The efficacy of ondansetron in 75 children aged 6 to 48 months was investigated in an open-label,
non-comparative, single-arm study (S3A40320). All children received three 0.15 mg/kg doses of
intravenous ondansetron, administered 30 minutes before the start of chemotherapy and then
at four and eight hours after the first dose. Complete control of emesis was achieved in 56% of
patients.
Another open-label, non-comparative, single-arm study (S3A239) investigated the efficacy of one
intravenous dose of 0.15 mg/kg ondansetron followed by two oral ondansetron doses of 4 mg for
children aged < 12 yrs and 8 mg for children aged ≥ 12 yrs (total no. of children n= 28). Complete
control of emesis was achieved in 42% of patients.
PONV
The efficacy of a single dose of ondansetron in the prevention of post-operative nausea
and vomiting was investigated in a randomised, double-blind, placebo-controlled study in
670 children aged 1 to 24 months (post-conceptual age ≥44 weeks, weight ≥3 kg). Included
subjects were scheduled to undergo elective surgery under general anaesthesia and had an
ASA status ≤III. A single dose of ondansetron 0.1 mg/kg was administered within five minutes
following induction of anaesthesia. The proportion of subjects who experienced at least one
emetic episode during the 24-hour assessment period (ITT) was greater for patients on placebo
than those receiving ondansetron ((28% vs. 11%, p <0.0001).
Four double-blind, placebo-controlled studies have been performed in 1469 male and female
patients (2 to 12 years of age) undergoing general anaesthesia. Patients were randomised to
either single intravenous doses of ondansetron (0.1 mg/kg for paediatric patients weighing
40 kg or less, 4 mg for paediatric patients weighing more than 40 kg; number of patients = 735))
or placebo (number of patients = 734). Study drug was administered over at least 30 seconds,
immediately prior to or following anaesthesia induction. Ondansetron was significantly more
effective than placebo in preventing nausea and vomiting. The results of these studies are
summarised in Table 3.
Table 3 Prevention and treatment of PONV in Paediatric Patients – Treatment response over
24 hours
Study
S3A380
S3GT09
S3A381
S3GT11
S3GT11

Endpoint
CR
CR
CR
no nausea
no emesis

Ondansetron %
68
61
53
64
60

Placebo
39
35
17
51
47

% p value
0.001
0.001
0.001
0.004
0.004

CR = no emetic episodes, rescue or withdrawal
5.2. Pharmacokinetic properties
Following oral administration, ondansetron is passively and completely absorbed from the
gastrointestinal tract and undergoes first pass metabolism. Peak plasma concentrations of
about 30ng/ml are attained approximately 1.5 hours after an 8mg dose. For doses above 8mg
the increase in ondansetron systemic exposure with dose is greater than proportional; this may
reflect some reduction in first pass metabolism at higher oral doses. Bioavailability, following oral
administration, is slightly enhanced by the presence of food but unaffected by antacids. Studies
in healthy elderly volunteers have shown slight, but clinically insignificant, age-related increases
in both oral bioavailability (65%) and half-life (five hours) of ondansetron. Gender differences
were shown in the disposition of ondansetron, with females having a greater rate and extent of
absorption following an oral dose and reduced systemic clearance and volume of distribution
(adjusted for weight). The disposition of ondansetron following oral, intramuscular (IM) and
intravenous (IV) dosing is similar with a terminal half life of about three hours and steady state
volume of distribution of about 140L. Equivalent systemic exposure is achieved after IM and IV
administration of ondansetron.
A 4mg intravenous infusion of ondansetron given over five minutes results in peak plasma
concentrations of about 65ng/ml. Following intramuscular administration of ondansetron, peak
plasma concentrations of about 25ng/ml are attained within 10 minutes of injection.
Following administration of ondansetron suppository, plasma ondansetron concentrations
become detectable between 15 and 60 minutes after dosing.
Concentrations rise in an essentially linear fashion, until peak concentrations of 20-30ng/ml are
attained, typically six hours after dosing. Plasma concentrations then fall, but at a slower rate
than observed following oral dosing due to continued absorption of ondansetron. The absolute
bioavailability of ondansetron from the suppository is approximately 60% and is not affected by
gender. The half life of the elimination phase following suppository administration is determined
by the rate of ondansetron absorption, not systemic clearance and is approximately six hours.
Females show a small, clinically insignificant, increase in half-life in comparison with males.
Ondansetron is not highly protein bound (70-76%). Ondansetron is cleared from the systemic
circulation predominantly by hepatic metabolism through multiple enzymatic pathways. Less than
5% of the absorbed dose is excreted unchanged in the urine. The absence of the enzyme CYP2D6
(the debrisoquine polymorphism) has no effect on ondansetron's pharmacokinetics.
The pharmacokinetic properties of ondansetron are unchanged on repeat dosing.
Special Patient Populations
Children and Adolescents (aged 1 month to 17 years)
In paediatric patients aged 1 to 4 months (n=19) undergoing surgery, weight normalised clearance

6. CONTENTS OF THE PACK AND OTHER INFORMATION
What Ondansetron solution for injection or infusion
contains
• The active substance
is Ondansetron
(as Ondansetron
hydrochloride
dihydrate).
• Each ampoule
contains either 4mg
or 8mg Ondansetron
(as Ondansetron
hydrochloride
dihydrate)
• The other ingredients
are sodium chloride,
sodium citrate, citric
acid monohydrate and
water for injections
• This medicinal product contains less than 1 mmol sodium
(23mg) per ampoule, i.e. essentially 'sodium-free'.
What Ondansetron solution for injection or infusion looks
like and contents of the pack
Ondansetron 2mg/ml Solution for Injection or Infusion is a
clear colourless solution.
Ondansetron Injection is available in 1, 5, or 10, ampoules at
2 ml or 1, 5, or 10, at 4 ml.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Wockhardt UK Limited, Ash Road North, Wrexham,
LL13 9UF, United Kingdom.
Manufacturer
CP Pharmaceuticals Limited, Ash Road North, Wrexham,
L13 9UF, United Kingdom.
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Product name
Ondansetron 2mg/ml Solution
for Injection or Infusion

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This leaflet was last revised in 04/2016
104878/6

was approximately 30% slower than in patients aged 5 to 24 months (n=22) but comparable to
the patients aged 3 to 12 years. The half-life in the patient population aged 1 to 4 month was
reported to average 6.7 hours compared to 2.9 hours for patients in the 5 to 24 month and
3 to 12 year age range. The differences in pharmacokinetic parameters in the 1 to 4 month patient
population can be explained in part by the higher percentage of total body water in neonates and
infants and a higher volume of distribution for water soluble drugs like ondansetron.
In paediatric patients aged 3 to 12 years undergoing elective surgery with general anaesthesia,
the absolute values for both the clearance and volume of distribution of ondansetron were
reduced in comparison to values with adult patients. Both parameters increased in a linear
fashion with weight and by 12 years of age, the values were approaching those of young adults.
When clearance and volume of distribution values were normalised by body weight, the values for
these parameters were similar between the different age group populations. Use of weight-based
dosing compensates for age-related changes and is effective in normalising systemic exposure in
paediatric patients.
Population pharmacokinetic analysis was performed on 428 subjects (cancer patients, surgery
patients and healthy volunteers) aged 1 month to 44 years following intravenous administration of
ondansetron. Based on this analysis, systemic exposure (AUC) of ondansetron following oral or IV
dosing in children and adolescents was comparable to adults, with the exception of infants aged
1 to 4 months. Volume was related to age and was lower in adults than in infants and children.
Clearance was related to weight but not to age with the exception of infants aged 1 to 4 months.
It is difficult to conclude whether there was an additional reduction in clearance related to age in
infants 1 to 4 months or simply inherent variability due to the low number of subjects studied in
this age group. Since patients less than 6 months of age will only receive a single dose in PONV
a decreased clearance is not likely to be clinically relevant.
In patients with renal impairment (creatinine clearance 15-60 ml/min), both systemic clearance
and volume of distribution are reduced following IV administration of ondansetron, resulting in a
slight, but clinically insignificant, increase in elimination half-life (5.4h). A study in patients with
severe renal impairment who required regular haemodialysis (studied between dialyses) showed
ondansetron's pharmacokinetics to be essentially unchanged following IV administration.
Specific studies in the elderly or patients with renal impairment have been limited to IV and oral
administration. However, it is anticipated that the half-life of ondansetron after rectal administration
in these populations will be similar to that seen in healthy volunteers, since the rate of elimination
of ondansetron following rectal administration is not determined by systemic clearance.
Following oral, intravenous or intramuscular dosing in patients with severe hepatic impairment,
ondansetron's systemic clearance is markedly reduced with prolonged elimination half-lives
(15-32 h) and an oral bioavailability approaching 100% due to reduced pre-systemic metabolism.
The pharmacokinetics of ondansetron following administration as a suppository have not been
evaluated in patients with hepatic impairment.
5.3. Preclinical safety data
No additional data of relevance.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Citric acid monhydrate
Sodium citrate
Sodium chloride
Water for injections.
6.2. Incompatibilities
Ondansetron injection should not be administered in the same syringe or infusion as any other
medication.
6.3. Shelf life
36 months (unopened).
After dilution, see section 6.4 Special precautions for storage.
6.4. Special precautions for storage
Do not store above 25°C.
Keep the ampoule in the outer carton
Keep out of the reach and sight of children
After dilution:Chemical and physical in use stability has been demonstrated for 24 hours at 25°C and 5°C.
From a microbiological point of view, the product should be used immediately. If not used
immediately, in-use storage times and conditions prior to use are the responsibility of the user
and would not normally be longer than 24 hours at 2-8°C, unless opening and dilution has taken
place in controlled and validated aseptic conditions.
6.5. Nature and contents of container
Type I Ph Eur amber glass 3ml capacity ampoules. Each pack contains one, five or ten ampoules.
6.6. Special precautions for disposal
For single use. Discard any unused product immediately after use.
Ondansetron injection should not be autoclaved.
Compatibility with intravenous fluids:
Ondansetron injection should only be admixed with those infusion solutions which are
recommendedSodium Chloride Intravenous Infusion BP 0.9%w/v
Glucose Intravenous Infusion BP 5%w/v
Mannitol Intravenous Infusion BP 10%w/v
Ringers Intravenous Infusion
Potassium Chloride 0.3%w/v and Sodium Chloride 0.9%w/v Intravenous Infusion BP
Potassium Chloride 0.3%w/v and Glucose 5%w/v Intravenous Infusion BP
In keeping with good pharmaceutical practice dilutions of Ondansetron Injection in intravenous
fluids should be prepared at the time of infusion although chemical and physical in use stability
after dilution has been demonstrated for 24 hours at 25°C and 5°C.
Compatibility with other drugs: Ondansetron may be administered by intravenous infusion at
1mg/hour, e.g. from an infusion bag or syringe pump. The following drugs may be administered
via the Y-site of the ondansetron giving set for ondansetron concentrations of 16 to
160 micrograms/ml (e.g. 8 mg/500 ml and 8 mg/50 ml respectively):
Cisplatin: Concentrations up to 0.48 mg/ml (e.g. 240 mg in 500 ml) administered over one to
eight hours.
5 -Fluorouracil: Concentrations up to 0.8 mg/ml (e.g. 2.4g in 3 litres or 400mg in 500ml)
administered at a rate of at least 20ml per hour (500 ml per 24 hours). Higher concentrations of
5-fluorouracil may cause precipitation of ondansetron. The 5-fluorouracil infusion may contain up
to 0.045%w/v magnesium chloride in addition to other excipients shown to be compatible.
Carboplatin: Concentrations in the range 0.18mg/ml to 9.9mg/ml (e.g. 90mg in 500ml to 990mg
in 100ml), administered over ten minutes to one hour.
Etoposide: Concentrations in the range 0.14 mg/ml to 0.25 mg/ml (e.g. 72mg in 500ml to 250 mg
in 1 litre), administered over thirty minutes to one hour.
Ceftazidime: Doses in the range 250 mg to 2000 mg reconstituted with Water for Injections BP as
recommended by the manufacturer (e.g. 2.5ml for 250mg and 10ml for 2g ceftazidime) and given
as an intravenous bolus injection over approximately five minutes.
Cyclophosphamide: Doses in the range 100mg to 1g, reconstituted with Water for Injections
BP, 5ml per 100mg cyclophosphamide, as recommended by the manufacturer and given as an
intravenous bolus injection over approximately five minutes.
Doxorubicin: Doses in the range 10-100mg reconstituted with Water for Injections BP, 5ml per
10mg doxorubicin, as recommended by the manufacturer and given as an intravenous bolus
injection over approximately five minutes.
Dexamethasone: Dexamethasone sodium phosphate 20mg may be administered as a slow
intravenous injection over two to five minutes via the Y-site of an infusion set delivering
8 or 16mg of ondansetron diluted in 50-100ml of a compatible infusion fluid over approximately
15 minutes. Compatibility between dexamethasone sodium phosphate and ondansetron has
been demonstrated supporting administration of these drugs through the same giving set
resulting in concentrations in line of 32 micrograms to 2.5mg/ml for dexamethasone sodium
phosphate and |8 micrograms to 1mg/ml for ondansetron.
7. MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd
Ash Road North
Wrexham
LL13 9UF
U.K
8. MARKETING AUTHORISATION NUMBER(S)
PL 29831/0154
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Renewed: 06/11/2013
10. DATE OF REVISION OF THE TEXT
03/2016

104878/6

Measure bar should be 150mm at 100% scale

artwork.leicester@multipkg.com

Clearly mark any amendments on one proof and return to MPS

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
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the final responsibility must be taken by our client.
IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
FULL APPROVAL OF DESIGN AND TEXT.

Pharmacode: N/A

MPS Read Direction

FPO
Wockhardt Travel Direction

Customer

Wockhardt UK Limited

Colours Used

Description

Ondansetron Injection common leaflet Strides

Process Black

Item Code

104878/6

Text Free Area (non-printing)

Profile

As per uploaded pdf

Size

200 x 400mm

Min. Point Size

5.5pt (Main Body) / 5.5pt (Variables)

Market

UK

Language

English

Proof By

matt.pirie-scott

Proof No.

5

Date

20/04/2016

Artwork No.

652955

Keyline (Non-printing)

Pharma
Code

N/A

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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