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ONDANSETRON 2MG/ML SOLUTION FOR INJECTION OR INFUSION

Active substance(s): ONDANSETRON HYDROCHLORIDE DIHYDRATE

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Package leaflet: Information for the patient It is also used to prevent and treat sickness
ONDANSETRON 2 mg/ml SOLUTION FOR that can sometimes occur after an
INJECTION OR INFUSION
operation (adults only).
(Ondansetron)
2. WHAT YOU NEED TO KNOW BEFORE
ONDANSETRON SOLUTION FOR
INJECTION IS ADMINISTERED

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. W
 HAT 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).

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 betablocking 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
• 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.
Use in children aged over 6 months and
adolescents
The doctor will decide the dose. Look at the
label for more information.


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 postoperative nausea and vom ting (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 compatibil ty
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 w th 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 add tion 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 w th 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
Day 1 (a b)
<0.6m2 5 mg/m2 i.v. plus 2 mg syrup
after 12 hrs
≥0.6m2 5 mg/m2 i.v. plus 4 mg syrup
or tablet after 12 hrs

Days 2-6 (b)
2 mg syrup every
12 hrs
4 mg syrup or tablet
every 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
Day 1
≤ 10 Kg Up to 3 doses of 0.15mg/kg
every 4 hrs
≥ 10 Kg Up to 3 doses of 0.15mg/kg
every 4 hrs
(a b)

Days 2-6
2 mg syrup every
12 hrs
4 mg syrup or tablet
every 12 hrs
(b)

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 a teration 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-l fe
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
a tered 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
isted 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 hypersens tivity 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 beta-adrenergic 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 fo lowing 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 c inical 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
t. Specific studies have shown that there are no pharmacokinetic
interactions when ondansetron is administered with alcohol,
temazepam, furosemide, a fentanil, tramadol, morphine, lidocaine,
thiopental or propofol.
Ondansetron is metabolised by multiple hepatic cytochrome P-450
enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the mu tip icity 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 w th
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.
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. anthracyc ines) 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 estab ished.
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 hypersens tivity 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 defin tive evidence of
persistent c inical 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 w th 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). Man festations
that have been reported include visual disturbances, severe
constipation, hypotension and a vasovagal episode with transient
second degree AV block.
Paediatric population:
Paediatric cases consistent with serotonin syndrome have
been reported after inadvertent oral overdoses of ondansetron
(exceeded estimated ingestion of 4 mg/kg) in infants and ch ldren
aged 12 months to 2 years.
Treatment
There is no spec fic 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 receptorantagonist. ts 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

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.
Your doctor or nurse will give you or your
child ondansetron so it is unlikely that you
or your child will receive too much. If you
think you or your child 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)
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.

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.
Other formats:
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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
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This leaflet was last revised in 09/2016

106938/3


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 opiate induced 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 baselinecorrection 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 e ther
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 ora ly) 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-contro led 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). A l 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-b ind, placebo-controlled study in
670 ch ldren 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 ≤ II. A single dose of ondansetron
0.1 mg/kg was administered w thin 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

Endpoint

Ondansetron %

Placebo

% p value

S3A380

CR

68

39

0.001

S3GT09

CR

61

35

0.001

S3A381

CR

53

17

0.001

S3GT11

no nausea

64

51

0.004

S3GT11 no emesis 60
47
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 dispos tion 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 essentia ly 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 sma l, 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 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-l fe 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 d fferences 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
ch ldren 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.
t is d fficult 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 s ight, 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, t
is anticipated that the ha f-life of ondansetron after rectal
administration in these populations w ll 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 w th prolonged e imination 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 suppos tory 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 d lution, 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 d lution: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. f not used immediately, in-use storage times and
conditions prior to use are the responsibility of the user and
would not norma ly be longer than 24 hours at 2-8°C, unless
opening and dilution has taken place in controlled and validated
aseptic cond tions.
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 l tres
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. Compatib lity 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
09/2016

106938/3

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Source: Medicines and Healthcare Products Regulatory Agency

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