Adults:
Management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.
Prevention and treatment of post‐operative nausea and vomiting (PONV).
Paediatric Population:
Management of chemotherapy‐induced nausea and vomiting in children aged ≥6 months.
Prevention and treatment of post‐operative nausea and vomiting in children aged ≥ 1 month.

Posology
Chemotherapy and radiotherapy induced nausea and vomiting:
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 should be flexible in the range of 8‐32mg a day and selected as shown below.

Emetogenic chemotherapy and radiotherapy:
Ondansetron can be given either by rectal, oral (tablets or syrup), intravenous or intramuscular
administration.
For most patients receiving emetogenic chemotherapy or radiotherapy, Ondansetron 8mg should be
administered as a slow intravenous injection (in not less than 30 seconds) or intramuscular injection,
immediately before treatment followed by 8mg orally twelve hourly.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with
Ondansetron should be continued for up to 5 days after a course of treatment.
Highly emetogenic chemotherapy: For patients receiving highly emetogenic chemotherapy, e.g. highdose
Cisplatin, Ondansetron can be given either by oral, rectal, intravenous or intramuscular
administration. Ondansetron 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 injection (in not less than 30 seconds) or intramuscular
injection immediately before chemotherapy.
· A dose of 8mg by slow intravenous injection (in not less than 30 seconds) or intramuscular doses
of 8mg two to four hours apart, or by a constant infusion of 1mg/hour for up to 24 hours.
· A maximum initial intravenous dose of 16mg diluted in 50‐100ml of Saline or other compatible
infusion fluid (see Section 6.6) and infused over not less than 15 minutes immediately before
chemotherapy. The initial dose of Ondansetron may be followed by two additional 8mg
intravenous doses (in not less than 30 seconds) or intramuscular doses four hours apart.
· A single dose greater than 16mg must not be given due to dose dependent increase of QTprolongation
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 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 should be continued for up to 5 days after a course of treatment.
Paediatric Population:
CINV in children aged ≥6 months and adolescents:
The dose of CINV can be calculated based on body surface area (BSA) or weight – see below. In
paediatric clinical studies, Ondansetron was given by IV infusion diluted in 25 to 50ml of Saline or
other compatible infusion fluid and infused over not less than 15 minutes.
Weight‐based dosing results in higher total daily doses compared to BSA‐based dosing – see 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 Injection in the
prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use
of Ondansetron Injection for radiotherapy‐induced nausea and vomiting in children.
Dosing by BSA:
Ondansetron should be administered immediately before chemotherapy as a single intravenous
dose of 5mg/m2. The single intravenous dose must not exceed 8mg.
Oral dosing can commence twelve hours later and may be continued for up to 5 days. (Table 1).
The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32mg.
Table 1: BSA‐based dosing for Chemotherapy ‐ Children aged ≥6 months and adolescents

a The intravenous dose must not exceed 8mg.
b The total daily dose over 24 hours (given as divided doses) must not exceed adult dose of 32mg.
Dosing by bodyweight:
Weight‐based dosing results in higher total daily doses compared to BSA‐based dosing (see Sections
4.4 and 5.1).
Ondansetron should be administered immediately before chemotherapy as a single intravenous
dose of 0.15mg/Kg. The single intravenous dose must not exceed 8mg.
Two further intravenous doses may be given in 4‐hourly intervals.
Oral dosing can commence 12 hours later and may be continued for up to 5 days (Table 2).
The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32mg.
Table 2: Weight‐based dosing for Chemotherapy ‐ Children aged ≥6 months and adolescents

a The intravenous dose must not exceed 8mg.
b The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32mg.
Elderly:
In patients 65 to 74 years of age, the dose schedule for adults can be followed. All intravenous doses
should be diluted in 50‐100ml of Saline or other compatible infusion fluid (see Section 6.6) and
infused over 15 minutes.

In patients 75 years of age or older, the initial intravenous dose of Ondansetron should not exceed
8mg. All intravenous doses should be diluted in 50‐100ml of Saline or other compatible infusion fluid
(see Section 6.6) and infused over 15 minutes.
The initial dose of 8mg may be followed by two further intravenous doses of 8mg, infused over 15
minutes and given no less than four hours apart (see Section 5.2).
Patients with renal impairment:
No alteration of daily dosage or frequency of dosing, or route of administration is required.
Patients with Hepatic impairment:
Clearance of Ondansetron 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 and therefore parenteral or oral administration is recommended.
Patients with poor Sparteine/Debrisoquine metabolism:
The elimination half‐life of Ondansetron is not altered in subjects classified as poor metabolizers of
Sparteine 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 is required.
Post‐operative nausea and vomiting (PONV):
Adults:
For the prevention of PONV: Ondansetron can be administered orally or by intravenous or
intramuscular injection.
Ondansetron may be administered as a single dose of 4mg given by intramuscular or slow
intravenous injection at induction of anesthesia.
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 anesthesia, a
single dose of Ondansetron may be administered by slow intravenous injection (not less than 30
seconds) at a dose 0.1mg/Kg up to a maximum of 4mg either prior to, at or after induction of
anesthesia.
For the treatment of PONV after surgery in paediatric patients having surgery performed under
general anesthesia, 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.
There are no data on the use of Ondansetron in the treatment of PONV children below 2 years of
age.
Elderly:
There is limited experience in the use of Ondansetron in the prevention and treatment of PONV in
the elderly however Ondansetron 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 is required.

Patients with hepatic impairment:
Clearance of Ondansetron 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 and therefore parental or oral administration is recommended.
Patients with poor Sparteine/Debrisoquine metabolism:
The elimination half‐life of Ondansetron is not altered in subjects classified as poor metabolizers of
Sparteine 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.
Method of administration
For intravenous injection or intramuscular injection or intravenous infusion after dilution.
For instructions on dilution of the product before administration, see Section 6.6
Prescribers intending to use Ondansetron in the prevention of delayed nausea and vomiting
associated with chemotherapy or radiotherapy in adults, adolescents or children should take into
consideration current practice and appropriate guidelines

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to
other selective 5HT3 receptor antagonists.
Respiratory events should be treated symptomatically and clinicians should pay particular attention
to them as precursors of hypersensitive reactions.
Ondansetron prolongs the QT interval in a dose‐dependent manner (see Section 5.1). In addition,
post‐marketing cases of Torsade de Pointes have been reported in patients using Ondansetron.
Avoid Ondansetron in patients with congenital long QT syndrome. Ondansetron should be
administered with caution to patients who have or may develop prolongation of QTc, including
patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias patients taking
other medicinal products that lead to QT prolongation or electrolyte abnormalities.
Hypokalemia and hypomagnesemia should be corrected prior to Ondansetron administration.
There have been post‐marketing reports describing patients with Serotonin Syndrome (including
altered mental status, autonomic instability and neuromuscular abnormalities) following the
concomitant use of Ondansetron and other serotonergic drugs (including Selective Serotonin
Reuptake Inhibitors (SSRI) and Serotonin Noradrenaline Reuptake Inhibitors (SNRIs)). If concomitant
treatment with Ondansetron and other serotonergic drugs is clinically warranted, appropriate
observation of the patient is advised.

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.
Ondansetron Accord contains 2.5mmol (or 57.9mg) sodium per maximum daily dose of 32mg. To be
taken into consideration by patients on a controlled Sodium Diet.
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‐hour 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 (see Section 5.1).

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, Temazepan.
Ondansetron is metabolized by multiple hepatic cytochrome P‐450 enzymes: CYP3A4, CYP2D6 and
CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolizing 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.
Caution should be exercised when Ondansetron is coadministered with drugs that prolong the QT
interval and/or cause electrolyte abnormalities (See Section 4.4).
Use of Ondansetron with QT prolonging drugs may result in additional QT prolongation.
Concomitant use of Ondansetron with cardiotoxic drugs (e.g. Anthracyclines (such as Doxorubicin,
Daunorubicin or Trastuzumab), Antibiotics (such as Erythromycin), Antifungals (such as
Ketoconazole), Antiarrhythmics (such as Amiodarone) and Beta Blockers (such as Atenolol or
Timolol) may increase the risk of arrhythmias (See Section 4.4).
Serotonergic Drugs (e.g. SSRIs and SNRIs):
There have been post‐marketing reports describing patients with Serotonin Syndrome (including
altered mental status, autonomic instability and neuromuscular abnormalities) following the
concomitant use of Ondansetron and other serotonergic drugs (including SSRIs and SNRIs) (See
Section 4.4)
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.

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 post‐natal
development. However as animal studies are not always predictive of human response the use of
Ondansetron in pregnancy is not recommended.
Breastfeeding
Tests have shown that Ondansetron passes into the milk of lactating animals. It is therefore
recommended that mothers receiving Ondansetron should not breastfeed their babies.
Fertility
There is no information on the effects of Ondansetron on human fertility.

In psychomotor testing, Ondansetron does not impair performance nor cause sedation. No
detrimental effects on such activities are predicted from the pharmacology of Ondansetron.

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 and <1/10)
Uncommon ( 1/1000 to <1/100)
Rare ( 1/10,000 and <1/1000)
&
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. The
adverse event profiles in children and adolescents were comparable to that seen in adults.
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)(1).
Rare: Dizziness during rapid IV administration.
Eye disorders
Rare: Transient visual disturbances (eg. blurred vision) predominantly during IV
administration.
Very rare: Transient blindness predominantly during intravenous administration(2).
Cardiac disorders
Uncommon: Arrhythmias, chest pain with or without ST segment depression, bradycardia.
Rare: QTc prolongation (including Torsade de Pointes).
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 (3).
General disorders and administration site conditions
Common: local IV injection site reactions.
1. Observed without definitive evidence of persistent clinical sequelae.
2. 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.
3. These events were observed commonly in patients receiving chemotherapy with Cisplatin.
Reporting of suspected adverse reactions
To report any side effect(s) in Saudi Arabia, please contact:
The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966‐11‐205‐7662
Call NPC at +966‐11‐2038222, Exts: 2317‐2356‐2353‐2354‐2334‐2340.
Toll free phone: 8002490000
E‐mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc

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.
Ondansetron prolongs the QT interval in a dose‐dependent fashion. ECG monitoring is
recommended in cases of overdose.
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.
Paediatric population
Paediatric cases consistent with Serotonin Syndrome have been reported after inadvertent oral
overdoses of Ondansetron (exceeded estimated ingestion of 4mg/kg) in infants and children aged 12
months to 2 years.

ATC code:‐ A04 Antiemetics and Antinauseants
ATC group:‐ A04AAO 1 Serotonin (5HT3) antagonist
Mechanism of Action
Ondansetron is a potent, highly selective 5HT3 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 vomiting reflex
by activating vagal afferents via 5HT3 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 Opiate‐induced emesis is not yet established.

QT Prolongation
The effect of Ondansetron on the QTc interval was evaluated in a double blind, randomized, placebo
and positive (Moxifloxacin) controlled, crossover study in 58 healthy adult men and women.
Ondansetron doses included 8mg and 32mg infused intravenously over 15 minutes. At the highest
tested dose of 32mg, the maximum mean (upper limit of 90% CI) difference in QTcF from placebo
after baseline‐correction was 19.6 (21.5) msec. At the lower tested dose of 8mg, the maximum mean
(upper limit of 90% CI) 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 randomized trial in 415 patients aged 1 to 18 years (S3AB3006). On
the days of chemotherapy, patients received either Ondansetron 5mg/m2 intravenous and
Ondansetron 4mg orally after 8 to 12 hours or Ondansetron 0.45mg/Kg intravenous and placebo
after 8 to 12 hours. Post‐chemotherapy both groups received 4mg Ondansetron syrup twice daily for
3 days. Complete control of emesis on worst day of chemotherapy was 49% (5mg/m2 intravenous
and Ondansetron 4mg orally) and 41% (0.45mg/Kg intravenous and placebo orally). Postchemotherapy
both groups received 4mg Ondansetron syrup twice daily for 3 days. There was no
difference in the overall incidence or nature of adverse events between the two treatment groups.
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 5mg/m2
intravenous together with 2‐4 mg Dexamethasone orally.
· 71% of the patients when Ondansetron was administered as a syrup at a dose of 8mg
together with 2 to 4 mg Dexamethasone orally on the days of chemotherapy.

Post‐chemotherapy both groups received 4mg Ondansetron syrup twice daily for 2 days. There was
no difference in the overall incidence or nature of adverse events between the two treatment
groups.
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 receive three 0.15mg/Kg doses of
intravenous Ondansetron, administered at 30 minutes before the start of chemotherapy and then at
4 and 8 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 0.15mg/Kg Ondansetron followed by two Ondansetron doses of 4mg for
children aged < 12 years and 8mg for children aged ≥ 12 years (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 randomized, 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 effective surgery under general anesthesia and had an ASA status ≤ III. A single

dose of Ondansetron 0.1mg/Kg was administered within five minutes following induction of
anesthesia. 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 anesthesia. Patients were randomized to either
single intravenous doses of Ondansetron (0.1mg/kg for paediatric patients weighing 40 kg or less,
4mg for paediatric patients weighing more than 40kg; number of patients = 735)) or placebo
(number of patients = 734). Study drug was administered over at least 30 seconds, immediately prior
to or following anesthesia induction. Ondansetron was significantly more effective than placebo in
preventing nausea and vomiting. The results of these studies are summarized in Table 3.
Table 3 Prevention and treatment of PONV in Paediatric Patients – Treatment response over 24
hours

CR = no emetic episodes, rescue or withdrawal

Absorption
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 8 mg, 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.
Following administration of ondansetron suppository, plasma ondansetron concentrations become
detectable between 15 and 60 minutes after dosing. Concentrations rise in an especially linear
fashion, until peak concentrations of 20‐30ng/ml are attained, typically 6 hours after dosing. Plasma
concentrations then fall, but at a slower rate than observed following oral dosing due to continued
absorption of Ondansetron.
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.
A 4mg intravenous infusion of Ondansetron given over 5 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.
Distribution
The disposition of Ondansetron following oral, intramuscular (IM) and intravenous (IV) dosing is
similar with a terminal half‐life of about 3 hours and steady state volume of distribution of about 140
L. Equivalent systemic exposure is achieved after intramuscular and intravenous administration of
Ondansetron.

Ondansetron is not highly protein bound (70‐76%).
The absolute bioavailability of Ondansetron from the suppository is approximately 60% and is not
affected by gender.
Biotransformation
Ondansetron is cleared from the systemic circulation predominantly by hepatic metabolism through
multiple enzymatic pathways. The absence of the enzyme CYP2D6 (the Debrisoquine Polymorphism)
has no effect on Ondansetron's pharmacokinetics.
Elimination
Less than 5% of the absorbed dose is excreted unchanged in the urine. Terminal half‐life is about 3
hours.
The pharmacokinetic properties of Ondansetron are unchanged on repeat dosing.
The half‐life of the elimination phase following suppository administration is determined by the rate
of Ondansetron absorption, not systemic clearance and is approximately 6 hours. Females show a
small, clinically insignificant, increase in half‐life in comparison with males.
Special Patient Populations
Gender
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).
Children and Adolescents (aged 1 month to 17 years)
In paediatric patients aged 1 to 4 months (n=19) undergoing surgery, weight normalized 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 anesthesia, 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 normalized 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 normalizing 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.
Elderly
Early Phase I studies in healthy elderly volunteers have showed a slight age‐related decrease in
clearance, and an increase in half‐life of Ondansetron. However, wide inter‐subject variability
resulted in considerable overlap in pharmacokinetic parameters between young (< 65 years of age)
and elderly subjects (≥ 65 years of age) and there were no overall differences in safety or efficacy
observed between young and elderly cancer patients enrolled in CINV clinical trials to support a
different dosing recommendation for the elderly.
Based on more recent Ondansetron plasma concentrations and exposure‐response modelling, a
greater effect on QTcF is predicted in patients ≥ 75 years of age compared to young adults. Specific
dosing information is provided for patients over 65 years of age and over 75 years of age for IV
dosing (see Section 4.2).
Renal impairment
In patients with renal impairment (Creatinine clearance 15‐60ml/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 intravenous administration.
Hepatic impairment
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
hours) and an oral bioavailability approaching 100% due to reduced pre‐systemic metabolism. The
pharmacokinetics of Ondansetron following

Preclinical data revealed no special hazard for humans based on conventional studies of safety
pharmacology, repeated‐dose toxicity, genotoxicity and carcinogenic potential.
Ondansetron and its metabolites accumulate in the milk of rats at a milk:plasma ratio of 5.2:1.
A study in cloned human cardiac ion channels has shown Ondansetron has the potential to affect
cardiac repolarization via blockade of HERG potassium channels.

6.1 List of excipients
Citric acid monohydrate
Sodium citrate
Sodium chloride
Sodium hydroxide (for pH adjustment)
Hydrochloric acid, concentrated (for pH adjustment)
Water for injection

This medicinal product must not be mixed with other medicinal products except those mentioned in
Section 6.6.

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack. The expiry date refers to
the last day of that month.
Do not store above 30°C. Store in the original pack in order to protect from light.
Do not use this medicine if container is damaged.
Do not use this medicine if you notice that the solution is not clear or contains particles.
For storage conditions of the diluted medicinal product, see section 6.3.

Ondron 2mg/ml solution for injection or infusion is filled in Type I glass ampoule.
Each pack contains 5 or 10 ampoules.
Not all pack sizes may be marketed.

The solution must not be sterilized in an autoclave.
Ondron should only be admixed with those infusion solutions which are recommended:
 Sodium 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
The stability of Ondansetron Injection after dilution with the recommended infusion fluids have
been demonstrated in concentrations 0.016mg/ml and 0.64mg/ml.
Compatibility studies have been undertaken in Polyvinyl Chloride infusion bags with Polyvinyl
Chloride administration sets, Polyethylene infusion bags, Type 1 glass bottles and Polypropylene
syringes. Dilutions of Ondansetron Injection in 10% Mannitol injection, Ringer’s injection, 0.3%
Potassium Chloride and 0.9% Sodium Chloride injection, 0.3% Potassium Chloride and 5% Dextrose
Injection, 0.9% Sodium Chloride injection and 5% Glucose Injection have been demonstrated to be
stable in Polyvinyl Chloride infusion bags and Polyvinyl Chloride administration sets, Polyethylene
infusion bags, Type 1 glass bottles and Polypropylene syringes.
Compatibility with other drugs: Ondron may be administered by intravenous infusion using 0.9%
Sodium Chloride and 5% Dextrose injection at 1mg/hour, e.g. from an infusion bag or syringe pump.
The following drugs may be administered via the Y‐site of the Ondron giving set for Ondansetron
concentrations of 16 to 160micrograms/ml (e.g. 8mg/500ml and 8mg/50ml respectively);
Cisplatin: Concentrations up to 0.48mg/ml (e.g. 240mg in 500ml) administered over one to eight
hours.
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 0.14mg/ml to 0.25mg/ml (e.g. 72mg in 500ml to 250mg in 1
litre), administered over thirty minutes to one hour.
Ceftazidime: Doses in the range 250mg to 2000mg reconstituted with Water for Injection 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 Injection 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 Injection BP, 5ml per 10mg
Doxorubicin, as recommended by the manufacturer and given as an intravenous bolus injection over
approximately 5 minutes.

Dexamethasone: Dexamethasone Sodium Phosphate 20mg may be administered as a slow
intravenous injection over 2‐5 minutes via the Y‐site of an infusion set delivering 8 or 16mg of
Ondansetron diluted in 50‐100 ml 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 microgram ‐ 2.5mg/ml for Dexamethasone Sodium Phosphate and 8
microgram – 0.75mg/ml for Ondansetron.
The solution is to be visually inspected prior to use (also after dilution). Only clear solutions
practically free from particles should be used.
The diluted solutions should be stored protected from light.
Any unused product or waste material should be disposed of in accordance with local requirements.