Skip to Content

UK Edition. Click here for US version.

ONDANSETRON KABI 2 MG/ML SOLUTION FOR INJECTION

Active substance(s): ONDANSETRON HYDROCHLORIDE DIHYDRATE

View full screen / Print PDF » Download PDF ⇩
Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Ondansetron Kabi 2 mg/ml solution for injection

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml solution for injection contains:
Ondansetron hydrochloride dihydrate equivalent to 2 mg ondansetron.
Each ampoule with 2 ml contains 4 mg ondansetron.
Each ampoule with 4 ml contains 8 mg ondansetron.
1 ml solution for injection contains 3.34 mg of sodium as sodium citrate dihydrate
and sodium chloride.
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Solution for injection
Clear and colourless solution

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Adults:
Ondansetron is indicated for the prevention and treatment of nausea and vomiting
induced by cytotoxic chemotherapy and radiotherapy
Ondansetron is also indicated for the prevention and treatment of post-operative
nausea and vomiting (PONV).

Paediatric Population:

Ondansetron is indicated for the management of chemotherapy-induced nausea and
vomiting (CINV) in children aged ≥6 months, and for prevention and treatment of
PONV in children aged ≥1 month.

4.2

Posology and method of administration
For intravenous injection or for intravenous infusion after dilution.
For instructions on dilution of the product before administration, see section 6.6.
Chemotherapy and radiotherapy induced nausea and vomiting (CINV and RINV)

Adults
The emetogenic potential of cancer treatment varies according to the doses and
combinations of chemotherapy and radiotherapy regimens used. The selection of dose
regimen should be determined by the severity of the emetogenic challenge.
Emetogenic chemotherapy and radiotherapy
For patients receiving emetogenic chemotherapy or radiotherapy ondansetron can be
given either by intravenous or oral administration.
The recommended intravenous dose of ondansetron is 8 mg administered as a slow
intravenous injection in not less than 30 seconds immediately before treatment.
Oral or rectal treatment is recommended to protect against delayed or prolonged
emesis after the first 24 hours.
For oral or rectal administration refer to the SmPC of ondansetron tablets and
suppositories, respectively.
Highly emetogenic chemotherapy e.g. High-dose cisplatin
Ondansetron may be administered as a single 8 mg intravenous dose immediately
before chemotherapy. Doses of greater than 8 mg and up to a maximum of 16 mg of
ondansetron may only be given by intravenous infusion diluted in 50 to 100 ml of
saline or other compatible infusion fluid and infused over not less than 15 minutes. 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).)
For management of highly emotogenic chemotherapy, a dose of 8 mg may be
administered by slow intravenous injection in not less than 30 seconds, followed by
two further intravenous doses of 8 mg two to four hours apart, or by a constant
infusion of 1 mg/hour for up to 24 hours.
The efficacy of ondansetron in highly emetogenic chemotherapy may be enhanced by
the addition of a single intravenous dose of dexamethasone sodium phosphate, 20 mg
administered prior to chemotherapy.

Oral or rectal treatment is recommended to protect against delayed or prolonged
emesis after the first 24 hours.
For oral or rectal administration refer to the SmPC of ondansetron tablets and
suppositories, respectively.

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. In paediatric clinical studies, ondansetron was given by intravenous
infusion diluted in 25 to 50 ml of saline or other compatible infusion fluid (see
Instructions for Use and Handling) 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)
Ondansetron 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 in the
prevention of chemotherapy-induced delayed or prolonged nausea and vomiting.
There are no data from controlled clinical trials on the use of ondansetron 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 intravenous dose must not exceed 8 mg.
Oral dosing can commence twelve hours later and may be continued for up to 5 days.
See Table 1 below.
The total daily dose must not exceed adult dose of 32mg
Table 1: BSA-based dosing for Chemotherapy - Children aged ≥6 months and
adolescents

BSA
< 0.6 m2
> 0.6 m2

Day 1a,b
5 mg/m2 i.v. plus 2 mg syrup or
tablet after 12 hours
5 mg/m2 i.v. plus 4 mg syrup or
tablet after 12 hours

a The intravenous dose must not exceed 8mg.

Days 2-6b
2 mg syrup or tablet after
12 hours
4 mg syrup or tablet after
12 hours

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 (see sections 4.4 and 5.1)
Ondansetron should be administered immediately before chemotherapy as a single
intravenous dose of 0.15mg/Kg. The intravenous dose must not exceed 8mg.
Two further intravenous doses may be given in 4-hourly intervals. The total daily
dose must not exceed adult dose of 32mg.
Oral dosing can commence twelve hours later and may be continued for up to 5 days.
See Table 2 below.
Table 2: Weight-based dosing for Chemotherapy - Children aged ≥6 months and
adolescents

Weight
10 kg
> 10 kg

Day 1a,b
Up to 3 doses of 0.15 mg/kg every
4-hours
Up to 3 doses of 0.15 mg/kg every
4-hours

Days 2-6b
2 mg syrup or tablet after
12 hours
4 mg syrup or tablet after
12 hours

a The intravenous dose must not exceed 8mg.
b The total daily dose must not exceed adult dose of 32 mg.

Elderly
Ondansetron is well tolerated by patients over 65 years and no alteration of dosage,
dosing frequency or route of administration is required.
Renal impairment
No alteration of daily dosage or frequency of dosing, or route of administration are
required.
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 8 mg should not be exceeded.
Patients with poor sparteine/debrisoquine metabolism
The elimination half-life of ondansetron is not altered in subjects classified as poor
metabolisers 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.

Post-operative nausea and vomiting (PONV)
Prevention of PONV
Adults:
For prevention of post-operative nausea and vomiting, the recommended dose of
ondansetron injection is a single dose of 4 mg by slow intravenous injection
administered at the induction of anaesthesia.
Treatment of established PONV
For treatment of established PONV a single dose of 4 mg given by slow intravenous
injection is recommended.

Paediatric population:
Post-operative nausea and vomiting 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 0.1 mg/kg up to a maximum
of 4 mg 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 may be
administered by slow intravenous injection (not less than 30 seconds) at a dose of
0.1mg/kg up to a maximum of 4 mg.
There are no data on the use of ondansetron for treatment of postoperative vomiting
in children under 2 years of age.

Elderly
There is limited experience in the use of ondansetron in the prevention and treatment
of post-operative nausea and vomiting (PONV) in the elderly, however ondansetron is
well tolerated in patients over 65 years receiving chemotherapy.

Special Populations
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 8 mg should not be exceeded.
Patients with poor sparteine/debrisoquine metabolism
The elimination half-life of ondansetron is not altered in subjects classified as poor
metabolisers 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.

4.3

Contraindications
Concomitant use with apomorphine (see Interactions with other medicinal products).
Hypersensitivity to any component of the preparation

4.4

Special warnings and precautions for use
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 hypersensitivity reactions.
Ondansetron prolongs the QT interval in a dose-dependent manner (see Clinical
Pharmacology). 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 or 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
sub-acute 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.

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 regimes has not been investigated in clinical trials. Cross trial comparing
indicate similar efficacy for both regimes (see section 5.1)
This medicinal product contains 2.3 mmol (or 53.5 mg) sodium per dose. To be taken
into consideration by patients on a controlled sodium diet.

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 coadministered with it. Specific studies have shown that there
are no interactions when ondansetron is administered with alcohol, temazepam,
furosemide, alfentanil, tramadol, morphine, lignocaine, 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.
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 trastuzimab), antibiotics (such as
erythromycin or ketoconazole), antiarrhythmics (such as amiodarone) and beta

blockers (such as atenolol or timolol) may increase the risk of arrhythmias. (See
Special warnings and precautions for use).
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 Special warnings and precautions for use)

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.

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 peri- and post-natal development. However, as animal studies are not
always predictive of human response the use of ondansetron in pregnancy is not
recommended.
Lactation
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.

4.7

Effects on ability to drive and use machines
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 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)1
Rare:

Dizziness during rapid IV administration.

Eye disorders
Rare: Transient visual disturbances (e.g. blurred vision) predominantly during IV
administration.
Very rare:
Transient blindness predominantly during intravenous
administration2.

Cardiac disorders
Uncommon:
bradycardia.
Rare:

Arrhythmias, chest pain with or without ST segment depression,

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 tests3

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.

Paediatric population
The adverse event profiles in children and adolescents were comparable to that seen
in adults.

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 Undesirable effects). Manifestations that have been reported include visual
disturbances, severe constipation, hypotension and a vasovagal episode with transient
second-degree AV block.
Ondansetron prolongs QT interval in a dose-dependent manner. ECG monitoring is
recommended in cases of overdose.
Treatment
There is no specific antidote for ondansetron, therefore in 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
Pharmacotherapeutic group: Antiemetics and antinauseants, Serotonin (5HT3)
antagonists
ATC Code: A04AA01
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.
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,
randomized, 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% CI) 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% CI) difference in QTcF from placebo after baselinecorrection 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. Postchemotherapy 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. 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 5
mg/m2 intravenous together with 2 to 4 mg dexamethasone orally
• 71% of patients when ondansetron was administered as syrup at a dose of 8 mg
together with 2 to 4 mg dexamethasone orally on the days of chemotherapy.
Post-chemotherapy both groups received 4 mg 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 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

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 randomised, double-blind, placebocontrolled 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 24hour 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
The pharmacokinetic properties of ondansetron are unchanged on repeat dosing.
A direct correlation of plasma concentration and anti-emetic effect has not been
established.
Absorption
A 4 mg intravenous infusion of ondansetron given over 5 minutes results in peak
plasma concentrations of about 65 ng/ml.

Distribution
The disposition of ondansetron following oral, intramuscular (IM) and intravenous
(IV) dosing is similar with a steady state volume of distribution of about 140 L.
Equivalent systemic exposure is achieved after IM and IV administration of
ondansetron.
Ondansetron is not highly protein bound (70-76%).
Metabolism
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.
Excretion
Less than 5% of the absorbed dose is excreted unchanged in the urine. Terminal half
life is about 3 hours.
Special groups
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.

Elderly persons
Studies in healthy elderly volunteers have shown slight age-related increases in halflife (5 hours).
Renal impairment
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 (5.4 h). 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.
Hepatic impairment
In patients with severe hepatic impairment, ondansetron’s systemic clearance is
markedly reduced with prolonged elimination half-lives (15-32 h).
Gender differences
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).

5.3

Preclinical safety data
Preclinical data revealed no special hazard for humans based on conventional studies
of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential
and toxicity to reproduction.
Ondansetron and its metabolites accumulate in the milk of rats, milk/plasma-ratio was
5.2:1.
A study in cloned human cardiac ion channels has shown ondansetron has the
potential to affect cardiac repolarisation via blockade of HERG potassium channels.
The clinical relevance of this finding is uncertain.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sodium chloride
Sodium citrate dihydrate
Citric acid monohydrate
Water for injections

6.2

Incompatibilities
Ondansetron injection should not be administered in the same syringe or infusion as
any other medication.
Ondansetron injection should only be mixed with those infusion solutions that are
recommended in section 6.6.

6.3

Shelf life
Unopened:
4 years
Injection:
After first opening the medicinal product should be used immediately.
Infusion:
Chemical and physical in-use stability has been demonstrated for 48 hours at 25°C
with the solutions given in section 6.6.
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 normally not be longer than 24 hours at 2 to 8°C,
unless dilution has taken place in controlled and validated aseptic conditions.

The diluted solutions should be stored protected from light
6.4

Special precautions for storage
Keep the ampoules in the outer carton in order to protect from light.
For storage conditions of the diluted medicinal product, see section 6.3.

6.5

Nature and contents of container
Type I clear glass ampoules
2 ml:
Pack sizes: 1, 5 and 10 ampoules.

4 ml:
Pack sizes: 1, 5 and 10 ampoules.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local
requirements.
Ondansetron 2 mg/ml may be diluted with the following solutions for infusion:
Sodium chloride 9 mg/ml (0.9 % w/v) solution
Glucose 50 mg/ml (5 % w/v) solution
Mannitol 100 mg/ml (10 % w/v) solution
Ringer’s lactate solution
The diluted solutions should be stored protected from light.
Note:
Ondansetron injection ampoules should not be autoclaved.

7

MARKETING AUTHORISATION HOLDER
Fresenius Kabi Limited
Cestrian Court
Eastgate Way
Manor Park
Runcorn
Cheshire
WA7 1NT
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 08828/0176

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
11/05/2007

10

DATE OF REVISION OF THE TEXT
04/04/2016

Expand view ⇕

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.

Hide