ONDANSETRON ACCORD ondansetron (as hydrochloride dihydrate) 4 mg/2 mL solution for injection pre-filled syringe

Australia - English - Department of Health (Therapeutic Goods Administration)

Buy It Now

Active ingredient:
ondansetron hydrochloride dihydrate
Available from:
Accord Healthcare Pty Ltd
Authorization status:
Registered
Authorization number:
338224

Read the complete document

Version 5.0

Page 1 of 2

ONDANSETRON ACCORD

Ondansetron Solution Injection, 4 mg/2 mL and 8 mg/4 mL

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about Ondansetron Accord

Injection. It does not contain all the

available information.

It does not take the place of talking to

your doctor or pharmacist.

All medicines have risks and benefits.

Your doctor has weighed the risks of

you taking Ondansetron Accord

Injection against the benefits this

medicine is expected to have for you.

This medicine is likely to be used while

you are at the clinic or in hospital. If

possible, please read this leaflet

carefully before this medicine is given

to you. In some cases this leaflet may

be given to you after the medicine has

been used.

If you have any concerns about

taking this medicine, ask your doctor

or pharmacist.

Keep this leaflet.

You may need to read it again.

What Ondansetron

Accord is used for

Ondansetron Accord Injection contains

a medicine called ondansetron. This

belongs to a group of medicines called

antiemetics/antinauseants.

Ondansetron Accord Injection is used

to prevent the nausea (feeling sick) and

vomiting that may occur after surgery

or after therapy with anticancer

medicines (chemotherapy) or radiation.

Ondansetron Accord Injection may be

used for the management of other

conditions that are not mentioned

above. Your doctor will be able to tell

you about the specific condition for

which you have been prescribed

Ondansetron Accord Injection.

This medicine is available only with a

doctor’s prescription.

Before you are given

Ondansetron Accord

When you must not be

given it

Do not use Ondansetron Accord

Injection if:

you have an allergy to ondansetron

or any of the ingredients listed at

the end of this leaflet

you are pregnant or trying to

become pregnant

you are breastfeeding

you are taking apomorphine (used

to treat Parkinson’s disease)

If you are not sure whether any of these

apply to you, check with your doctor.

Before you are given it

Tell your doctor if:

you have any allergies to:

any other medicine

any other substances, such as

foods, preservatives or dyes

you are pregnant or intend to

become pregnant

you are breastfeeding or plan to

breastfeed

you have liver problems

you have an abnormal heart rhythm

(QT prolongation)

you have any blood problems,

including abnormal salt levels in

your blood.

Taking other medicines

Tell your doctor if you are taking

any other medicines, including any

that you buy without a prescription

from your pharmacy, supermarket

or health food shop.

Some medicines and ondansetron may

interfere with each other. These

include:

pain killers such as tramadol

antibacterials such as rifampicin

medicines that are known to lead to

an abnormal heart rhythm (QT

prolongation)

Your doctor will advise you about any

dosage adjustments needed and

continuing to take other medicines

while you are receiving Ondansetron

Accord Injection.

How Ondansetron

Accord is given

Ondansetron Accord Injection is given

by injection into the muscle or by slow

injection into a vein. It must only be

given by a doctor or nurse.

Your doctor will decide what dose and

how long you will receive Ondansetron

Accord Injection.

The clinical safety of Ondansetron in

children under 2 years has not been

established.

If you are given too much

(overdose)

This rarely happens as Ondansetron

Accord Injection is administered under

the care of a highly trained doctor.

However, if you are given too much

ondansetron, you may experience some

of the effects listed under “Side

Version 5.0

Page 2 of 2

effects” below.

Your doctor has information on how to

recognise and treat an overdose.

Ask your doctor if you have any

concerns.

Side Effects

Tell your doctor or nurse as soon as

possible if you do not feel well while

you are being given Ondansetron

Accord Injection or if your nausea

and vomiting does not go away.

Like other medicines, Ondansetron

Accord Injection can cause some side

effects. If they occur, most are likely to

be minor or temporary. However, some

may be serious and need medical

attention.

Ask your doctor or pharmacist to

answer any questions that you may

have.

Do not be alarmed by this list of

possible side effects. You may not

experience any of them.

Tell your doctor or nurse if you

notice any of the following:

headache

a sensation of warmth or flushing

mild stomach cramps

constipation or diarrhoea

dry mouth

pain, redness or burning at place of

injection

hiccups

These are all common side effects.

Tell your doctor or nurse

immediately if you notice any of the

following:

‘wheezy’ symptoms

chest pain or tightness of the chest

changes in the way your heart beats,

e.g. if you notice it beating faster or

slower than normal, or if it beats

irregularly or if it ‘throbs’

disturbance in heart rhythm

(sometimes causing a sudden loss

of consciousness)

patients may experience “serotonin

syndrome” (confusion, sweating,

unsteadiness, shaking, diarrhoea)

when Ondansetron Accord Injection

is taken in combination with other

serotonergic drugs can include

certain types of antidepressants,

opioid pain medicines such as

tramadol and fentanyl, and lithium.

Please note, this is not an

exhaustive list. Please discuss with

your pharmacist or doctor if you

have any concerns.

Severe skin reaction where the top

layer of the skin detaches from the

lower layers.

low blood pressure

fits or convulsions

swelling of the eyelids, face, lips,

mouth or throat which may cause

difficulty in swallowing or

breathing

skin rash, skin lumps or hives

blurred vision

dizziness

These are serious side effects, some

of which include symptoms of an

allergic reaction. You may need

urgent medical attention. Serious

side effects are rare.

Other side effects not listed above may

also occur in some patients.

Storage

Stored below 25°C. Protect from Light.

Disposal

Any Ondansetron Accord from a single

dose preparation which is not used, will

be disposed of in a safe manner by your

doctor or pharmacist.

Product Description

What it looks like

Ondansetron Accord Injection is a

clear, colourless to almost colourless

solution in a clear or amber glass

ampoules in packs of 5 or 10. Or in a

syringe in a 1 pack.

Not all presentations and pack sizes

may be marketed.

Ingredients

Active ingredient:

Ondansetron (as ondansetron

hydrochloride dihydrate)

Inactive ingredients:

sodium chloride

sodium citrate dihydrate

citric acid monohydrate

sodium hydroxide

hydrochloric acid

water for injections

Name and Address of the

Sponsor

Accord Healthcare Pty Ltd

Level 24, 570 Bourke Street

Melbourne, VIC, 3000

Australia

Australian Registration Numbers

Ampoule

4 mg/2 mL: AUST R 205594

8 mg/4 mL: AUST R 205599

Syringe

4 mg/2 mL: AUST R 338224

8 mg/4 mL: AUST R 338227

Date of Preparation

This leaflet was prepared on 09

November 2020.

Read the complete document

Page 1 of 14

AUSTRALIAN PRODUCT INFORMATION

ONDANSETRON ACCORD (ONDANSETRON) SOLUTION FOR INJECTION

1

NAME OF THE MEDICINE

Ondansetron hydrochloride dihydrate

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Ondansetron

Accord

Injection

contains

mg/mL

ondansetron

ondansetron

hydrochloride

dihydrate).

For the full list of excipients, see

Section 6.1 List of Excipients.

3

PHARMACEUTICAL FORM

Ondansetron Accord Injection is a clear, colourless to almost colourless, sterile, isotonic, preservative-

free solution.

4

CLINICAL PARTICULARS

4.1

T

HERAPEUTIC INDICATIONS

Ondansetron Accord injection is indicated:

for the prevention and treatment of nausea and vomiting induced by cytotoxic therapy and

radiotherapy.

for the prevention and treatment of post-operative nausea and vomiting.

4.2

D

OSE AND METHOD OF ADMINISTRATION

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 to 32 mg a day and selected as shown below. The lowest effective

dose should be used.

The product is for single use in one patient only. Discard any residue.

Use in adults

Emetogenic chemotherapy and radiotherapy:

For the control of chemotherapy or radiotherapy induced

emesis or nausea in adults, a single dose of ondansetron 8 mg should be administered as a slow

intravenous injection in not less than 30 seconds, immediately before treatment.

Highly emetogenic chemotherapy:

A single dose of ondansetron 8 mg by slow intravenous injection

immediately before chemotherapy has been shown to be effective in many patients.

Higher doses may be required in some patients, particularly those on high dose cisplatin, and the doses

should be adjusted according to the severity of the emetogenic challenge. If required, additional

intravenous doses may be given up to a maximum of 32 mg in 24 hours.

Intravenous doses of more than 8 mg should be given by slow intravenous infusion over at least 15

minutes, since rapid intravenous administration of ondansetron has been associated with a higher

incidence of transient visual disturbances. A single dose greater than 16 mg should not be given (see

Section 4.4 Special Warnings and Precautions for Use

Dexamethasone sodium phosphate as a single intravenous dose of 20 mg may be given prior to the first

intravenous

dose

ondansetron

before

chemotherapy,

potentiate

antiemetic

effects

ondansetron.

Post-operative nausea and vomiting (injection only):

For prevention of post-operative nausea and

vomiting in adults, ondansetron may be administered as a single dose of 4 mg, given by intramuscular

or slow intravenous injection at induction of anaesthesia.

Page 2 of 14

For treatment of established post-operative nausea and vomiting, a single dose of 4 mg given by

intramuscular or slow intravenous injection is recommended in most patients. If necessary, the dose

may be increased to 8 mg.

Use in children

Emetogenic chemotherapy and radiotherapy:

Experience is currently limited but ondansetron was

effective and well tolerated in children over 4 years of age, when given intravenously at a dose of 5

mg/m

over 15 minutes immediately before chemotherapy, followed by oral therapy, if required. The

dose of 5 mg/m

is based on limited data.

Post-operative nausea and vomiting (injection only):

For prevention of post-operative nausea and

vomiting in children aged 2 to 12 years having surgery under general anaesthesia, ondansetron may be

administered by slow intravenous injection at a dose of 0.1 mg/kg up to a maximum of 4 mg either prior

to, at, or after induction of anaesthesia.

For treatment of established post-operative nausea and vomiting, ondansetron may be administered by

slow intravenous injection at a dose of 0.1 mg/kg up to a maximum of 4 mg.

Repeat dosing has not been studied in paediatric patients who experience nausea and/or vomiting despite

receiving

ondansetron

prophylaxis

continue

experience

symptoms

after

ondansetron

treatment.

Use in the elderly

Emetogenic chemotherapy and radiotherapy:

Efficacy and tolerance in patients aged over 65 years was

similar to that seen in younger adults, indicating no need to alter dosage or route of administration in

the elderly.

Post-operative nausea and vomiting (injection only):

There is limited experience in the use of

ondansetron in the prevention and treatment of post-operative nausea and vomiting in the elderly.

Use in patients with impaired renal function

No alteration of daily dosage, frequency of dosing or route of administration is required.

Use in patients with impaired hepatic function

A study which investigated the effect of hepatic impairment on the pharmacokinetics of ondansetron in

24 subjects showed that the plasma clearance of ondansetron is reduced to about 20% of normal and the

serum half-life is significantly prolonged in subjects with severe impairment of hepatic function.

The results in patients with only mildly or moderately impaired hepatic function were less clear. The

study showed that in this group, the plasma clearance of ondansetron fell to about 50% of that seen in

healthy volunteers. Subjects with mild and moderate impairment were not distinguishable from each

other for any parameter. This was believed to be partly due to the lack of sensitivity of the Pugh

classification system in distinguishing between patients with mild or moderate impairment.

It is recommended that a total daily dose of 8 mg should not be exceeded for patients with moderate or

severe hepatic dysfunction. For optimum clinical effect, it is recommended that this total daily dose be

administered before chemotherapy or radiotherapy.

The severity of the liver disease was assessed according to Pugh’s modification of Child’s classification

(Pugh et al., Brit. J. Surg. 1973; 60 (8): 646-649). Patients with a Pugh score of 5 or less were considered

to have good hepatic function. A patient with a score of 6 was graded as having mild hepatic impairment,

7 to 9 as moderate hepatic impairment and 10 or more as severe hepatic impairment. The clinical

features used in the grading and the weighting system applied are shown in Table 1.

Table 1: Grading of hepatic impairment

Clinical and biochemical measurements

Points scored for increasing abnormality

1

2

3

Encephalopathy (grade)*

None

1 and 2

3 and 4

Page 3 of 14

Clinical and biochemical measurements

Points scored for increasing abnormality

1

2

3

Ascites

Absent

Slight

Moderate

Bilirubin (micromol/L)

17.1 - 34.2

34.2 - 51.3

> 51.3

Albumin (g/L)

28 - 35

< 28

Prothrombin time (seconds prolonged)

1 - 4

4 - 6

> 6

For primary biliary cirrhosis

Bilirubin (micromol/L)

17.1 - 68.4

68.4 - 171

> 171

* According to grading of Trey, Burns and Saunders (1966)

Use in patients with poor sparteine/debrisoquine metabolism

There were no significant differences among poor and extensive debrisoquine categorised metabolisers

with regard to ondansetron disposition (area under the curve, total systemic clearance, elimination half-

life) following a single 8 mg intravenous dose. The effect of repeated dosing was not investigated,

nevertheless dosage adjustments will probably not be required in patients receiving ondansetron by the

intravenous route.

Compatibility with other drugs

Administration recommendations: slow intravenous injection 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 microgram/mL (i.e. 8 mg/500 mL and 8 mg/50 mL respectively).

Cisplatin:

Concentrations of up to 0.48 mg/mL (i.e. 240 mg/500 mL) administered over one to eight

hours.

Carboplatin:

Concentrations in the range 0.18 to 9.9 mg/mL (i.e. 90 mg/500 mL to 990 mg/100 mL)

administered over ten minutes to one hour.

Fluorouracil:

Concentrations up to 0.8 mg/mL (i.e. 2.4 g in 3 litres or 400 mg in 500 mL) administered

at a rate of at least 20 mL per hour (500 mL per 24 hours). Higher concentrations of fluorouracil may

cause precipitation of ondansetron. The fluorouracil infusion may contain up to 0.045% w/v magnesium

chloride in addition to other excipients shown to be compatible.

Etoposide:

Concentrations in the range 0.14 to 0.25 mg/mL (i.e. 72 mg/500 mL to 250 mg/L)

administered over 30 minutes to one hour.

Ceftazidime:

Doses in the range 250 mg to 2 g reconstituted with Water for Injections BP as

recommended by the manufacturer (i.e. 2.5 mL for 250 mg and 10 mL for ceftazidime 2 g) and given

as an intravenous bolus injection over approximately five minutes.

Cyclophosphamide:

Doses in the range 100 mg to 1 g reconstituted with Water for Injections BP, 5 mL

per cyclophosphamide 100 mg, as recommended by the manufacturer, and given as an intravenous bolus

injection over approximately five minutes.

Doxorubicin:

Doses in the range 10 to 100 mg, 5 mL per doxorubicin 10 mg, as recommended by the

manufacturer, and given as an intravenous bolus injection over approximately five minutes.

Dexamethasone:

Dexamethasone sodium phosphate 20 mg may be administered as a slow intravenous

injection over 2-5 minutes. The intravenous administration of dexamethasone should be physically

separated from ondansetron either by administration via a different line or by flushing the line with

0.9% Sodium Chloride injection in between the two drugs.

Intravenous fluids

Ondansetron Injection should not be administered in the same syringe or infusion as any other

medication.

Ondansetron Injection should only be admixed with those infusion solutions which are recommended.

Ondansetron Injection has been shown to be stable for seven days when stored at room temperature

Page 4 of 14

(below 25°C) or in a refrigerator (2-8°C) with the following intravenous fluids: Sodium Chloride

Intravenous Infusion BP 0.9% w/v; Glucose Intravenous Infusion BP 5% w/v; Mannitol Intravenous

Infusion BP 10% w/v; Ringer’s 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.

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 Accord Injection in 10% mannitol injection, ringer’s injection, 0.3%

potassium chloride and 0.9% sodium chloride injection, 0.3% potassium chloride and 5% glucose

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.

Although the chemical and physical stability of Ondansetron Accord Injection diluted with the listed

intravenous infusion fluids has been demonstrated for seven days at room temperature (below 25°C) or

in a refrigerator (2-8°C), it is recommended that, in order to reduce microbial contamination hazards,

the diluted solutions should be prepared immediately prior to use and infusion commenced as soon as

practicable after preparation of the mixture. If storage is necessary, hold at 2°C-8°C. The diluted

infusion solution should be used within 24 hours and any residue discarded.

Diluted solutions which are hazy, discoloured or contain visible particulate matter must be discarded.

4.3

C

ONTRAINDICATIONS

Hypersensitivity to ondansetron or to any component of the preparation (see

Section 4.4 Special

Warnings and Precautions for Use

Based

reports

profound

hypotension

loss

consciousness

when

ondansetron

administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.

4.4

S

PECIAL WARNINGS AND PRECAUTIONS FOR USE

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other

selective 5HT

-receptor antagonists.

Ondansetron prolongs the QT interval in a dose-dependent manner. In addition, post-marketing cases

of Torsades 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.

Serotonin syndrome has been described following the concomitant use of ondansetron and other

serotonergic drugs (see

Section 4.5 Interactions with Other Medicines and Other Forms of

Interactions

). 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.

Repeat dosing has not been studied in paediatric patients who experience nausea and/or vomiting despite

receiving

ondansetron

prophylaxis

continue

experience

symptoms

after

ondansetron

treatment.

Use in hepatic impairment

Section 4.2 Dose and Method of Administration, Use in patients with impaired hepatic

function

Page 5 of 14

Use in renal impairment

Section 4.2 Dose and Method of Administration, Use in patients with impaired renal function.

Use in the elderly

Section 4.2 Dose and Method of Administration, Use in the elderly

Paediatric use

Section 4.2 Dose and Method of Administration, Use in children

Effects on laboratory tests

No data available.

4.5

I

NTERACTIONS WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS

There is no evidence that ondansetron either induces or inhibits the metabolism of other drugs

commonly co-administered with it; specific studies have been limited to alcohol, temazepam and

alfentanil to date.

Ondansetron is metabolised by multiple hepatic cytochrome P450 drug 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. Hence no dosage adjustment is recommended for patients on these drugs.

Caution should be exercised when ondansetron is co-administered with drugs that prolong the QT

interval and/or cause electrolyte abnormalities (see

Section 4.4 Special Warnings and Precautions

for Use

Based

reports

profound

hypotension

loss

consciousness

when

ondansetron

administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.

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.

Following a single 8 mg tablet dose of ondansetron, a threefold to fourfold decrease in the systemic

exposure has been seen in adult epileptic subjects maintained on chronic doses of carbamazepine (n = 8)

or phenytoin (n = 8) and not receiving chemotherapy. The effect of these enzyme inducing agents on

intravenous ondansetron has not been assessed, but the absence of any first pass effects would be

expected to result in a smaller change in exposure than seen following oral dosing. Due to the limited

efficacy data in subjects on antiepileptics and the many variables that may influence exposure and

response, the clinical significance of this drug interaction in cancer patients receiving chemotherapy is

not known.

Serotonergic Drugs (e.g. SSRIs and SNRIs)

Serotonin

syndrome

(including

altered

mental

status,

autonomic

instability

neuromuscular

abnormalities) has been described following the concomitant use of ondansetron and other serotonergic

drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake

inhibitors (SNRIs) (see

Section 4.4 Special Warnings and Precautions for Use

Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.

See also

Section 4.2 Dose and Method of Administration, Compatibility.

4.6

F

ERTILITY

,

PREGNANCY AND LACTATION

Effects of fertility

Oral doses of ondansetron up to 15 mg/kg/day in rats had no effect on male or female fertility.

Women of childbearing potential should consider the use of contraception.

Page 6 of 14

Use in pregnancy ( Category B1)

Based on human experience from epidemiological studies, ondansetron is suspected to cause orofacial

malformations when administered during the first trimester of pregnancy. In one cohort study including

1.8 million pregnancies, first trimester ondansetron use was associated with an increased risk of oral

clefts (3 additional cases per 10,000 women treated; adjusted relative risk, 1.24 (95% CI 1.03- 1.48)).

The available epidemiological studies or cardiac malformations show conflicting results. Animal studies

do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Ondansetron should not be used during the first trimester of pregnancy.

Use in lactation

Tests have shown that ondansetron is excreted in the breast milk of rats. It is therefore recommended

that mothers receiving ondansetron should not breastfeed their babies.

4.7

E

FFECTS ON ABILITY TO DRIVE AND USE MACHINES

The effects of this medicine on a person’s ability to drive and use machines were not assessed as part

of its registration.

4.8

A

DVERSE EFFECTS

(U

NDESIRABLE EFFECTS

)

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very

common (greater than or equal to 1/10), common (greater than or equal to 1/100 and < 1/10), uncommon

(greater than or equal to 1/1,000 and < 1/100), rare (greater than or equal to 1/10,000 and < 1/1,000)

and very rare (< 1/10,000), including isolated reports. 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

oculogyric crisis, dystonic reactions and dyskinesia have been observed without definitive evidence of

persistent clinical sequelae).

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 IV 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.

Rare:

QTc prolongation (including Torsades de Pointes).

Vascular disorders

Common:

Sensation of warmth or flushing.

Page 7 of 14

Uncommon:

Hypotension.

Respiratory, thoracic and mediastinal disorders

Uncommon:

Hiccups.

Gastrointestinal disorders

Common:

Constipation,

Xerostomia,

Local

anal/rectal

burning

sensation

following

insertion of suppositories.

Hepatobiliary disorders

Uncommon:

Asymptomatic increases in liver function tests

These events were observed commonly in patients receiving chemotherapy with cisplatin.

Skin and subcutaneous tissue disorders

Very rare:

Toxic skin eruption, including toxic epidermal necrolysis.

General disorders and administration site conditions

Common:

Local IV injection site reactions.

date,

there

been

limited

safety

experience

controlled

trials

following

intramuscular

administration.

Of 7,400 patients who received intravenous ondansetron during clinical trials, eleven experienced major

cardiovascular events, including three fatalities, which were considered to be drug-related by the

investigators (one probable, ten possible). It is well known that cardiovascular events, especially of a

vascular occlusive nature, are not uncommon among patients with cancer, and these events are further

increased with cytotoxic chemotherapy, particularly cisplatin.

Table 2 shows adverse events occurring in greater than or equal to 5% of paediatric patients (either

group) in three pivotal clinical trials for prevention of post-operative nausea and vomiting. Ondansetron

appears to be as well tolerated as placebo.

Table 2: Adverse events (frequency ≥ 1%) reported in three pivotal clinical trials in paediatric

patients for the prevention of post-operative nausea and vomiting.

Adverse event

Placebo

(n = 548)

Ondansetron

(n = 542)

Total patients with AE

309 (56%)

289 (53%)

Eye disorder

86 (16%)

102 (19%)

Wound problem

72 (13%)

70 (13%)

Anxiety/agitation

36 (7%)

42 (8%)

Drowsiness/sedation

44 (8%)

34 (6%)

Nausea and/or vomiting

62 (11%)

33 (6%)

Headache

32 (6%)

32 (6%)

Pyrexia

22 (4%)

21 (4%)

Disease: lower respiratory tract

6 (1%)

16 (3%)

Arrhythmia

15 (3%)

14 (3%)

Expectoration

16 (3%)

13 (2%)

Cough

13 (2%)

13 (2%)

Dizziness

11 (2%)

11 (2%)

Laryngospasm

10 (2%)

11 (2%)

Disturbance of conduct/behaviour

8 (1%)

10 (2%)

Hypoxia

6 (1%)

8 (1%)

Visual disturbance

11 (2%)

6 (1%)

Bradycardia

2 (< 1%)

6 (1%)

Throat disorder

2 (< 1%)

6 (1%)

Page 8 of 14

Adverse event

Placebo

(n = 548)

Ondansetron

(n = 542)

Bronchospasm/asthma

10 (2%)

5 (< 1%)

Swollen periocular area

6 (1%)

5 (< 1%)

Gastric symptoms

8 (1%)

4 (< 1%)

Poor oral intake

8 (1%)

4 (< 1%)

Pain

6 (1%)

4 (< 1%)

Haemorrhage

8 (1%)

3 (< 1%)

Ear disorder

6 (1%)

2 (< 1%)

The overall incidence of adverse events was similar for ondansetron (53%) and placebo (56%). The

most commonly reported adverse events were eye disorder(s) as a result of ophthalmic operations,

wound problems at the surgical site, nausea and/or vomiting, drowsiness/sedation, anxiety/agitation and

headache. These events are not unexpected in patients undergoing surgery and there was little difference

of these between treatment groups. However, the incidence of nausea and/or vomiting reported as an

adverse event was significantly higher in patients who had received placebo (11%) compared to those

who had received ondansetron (6%).

Table 3 shows adverse events occurring in greater than or equal to 1% of paediatric patients in one

pivotal clinical trial for treatment of post-operative nausea and vomiting.

Table 3: Adverse events (frequency ≥ 1%) reported in one pivotal clinical trial in paediatric

patients for treatment of post-operative nausea and vomiting

Adverse event

Placebo

(n = 183)

Ondansetron

(n = 192)

Nausea and/or vomiting

27 (15%)

18 (9%)

Wound problem

14 (8%)

11 (6%)

Pyrexia

19 (10%)

10 (5%)

Headache

11 (6%)

9 (5%)

Drowsiness/sedation

12 (7%)

7 (4%)

Anxiety/agitation

11 (6%)

7 (4%)

Disturbed behaviour

3 (2%)

4 (2%)

Hypoxia

1 (< 1%)

4 (2%)

Cough

5 (3%)

3 (2%)

Fewer adverse events were reported with ondansetron (36%) than with placebo (47%). The most

common adverse events were similar to those reported in clinical trials for the prevention of post-

operative nausea and vomiting.

Occasionally, local reactions at the site of intravenous injection have been reported.

Table 4 shows adverse events occurring in greater than or equal to 1% of adult patients receiving either

intravenous ondansetron or placebo for the prevention or treatment of post-operative nausea and

vomiting.

Table 4: Adverse events occurring in ≥ 1% of adult patients receiving ondansetron for the

prevention or treatment of post-operative nausea and vomiting

Adverse event

Placebo

(n = 842)

Ondansetron IV

(n = 1,998)

Headache

82 (10%)

220 (11%)

Dizziness

73 (9%)

144 (8%)

Constipation

25 (3%)

82 (4%)

Bradycardia

19 (2%)

60 (3%)

Drowsiness

18 (2%)

59 (3%)

Dysuria/Urinary Tract Infection

15 (2%)

53 (3%)

Injection Site Reaction

21 (2%)

47 (2%)

Shivering

20 (2%)

43 (2%)

Page 9 of 14

Adverse event

Placebo

(n = 842)

Ondansetron IV

(n = 1,998)

Nausea/Vomiting

15 (2%)

34 (2%)

Pruritis

9 (1%)

33 (2%)

Anxiety

12 (1%)

29 (1%)

Sleep Disturbance

5 (< 1%)

29 (1%)

Cough

6 (< 1%)

26 (1%)

Urinary retention

10 (1%)

24 (1%)

Rash

9 (1%)

21 (1%)

Abdominal Pain

9 (1%)

20 (< 1%)

Hypotension

14 (2%)

19 (< 1%)

Flatulence

9 (1%)

19 (< 1%)

The overall incidence rate was 45% in the placebo group and 47% in the intravenous ondansetron group.

The neurological body system was associated with the highest incidence of adverse events (placebo

approximately 23%; ondansetron 24%). These events were predominantly headache, dizziness and

drowsiness.

Cardiovascular adverse events (bradycardia and hypotension) occurred in approximately 4% in both

placebo

ondansetron

groups;

gastrointestinal

adverse

events

(constipation,

nausea/vomiting,

flatulence and abdominal pain) occurred in approximately 7% of patients both receiving placebo and

intravenous ondansetron.

The incidence rates were generally similar in both treatment groups for all body systems.

Reporting suspected adverse effects

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.

4.9

O

VERDOSE

Symptoms:

Little is known at present about overdosage with ondansetron, however, a limited number

of patients have received overdoses. Manifestations that have been reported include visual disturbances,

severe constipation, hypotension and a vasovagal episode with transient second degree AV block. In all

instances, the events resolved completely.

Treatment:

There is no specific antidote for ondansetron, therefore in cases of suspected overdose,

symptomatic and supportive therapy should be given as appropriate.

Ondansetron prolongs QT interval in a dose-dependent fashion. ECG monitoring is recommended in

cases of overdose.

For information on the management of overdose, contact the Poison Information Centre on 13 11 26

(Australia).

5

PHARMACOLOGICAL PROPERTIES

5.1

P

HARMACODYNAMIC PROPERTIES

Class of drug:

Antinauseant/antiemetic.

Mechanism of action

Ondansetron is a potent, highly selective 5HT

-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 5HT

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

Page 10 of 14

nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is due to antagonism of

-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

vomiting.

psychomotor

testing

ondansetron

does

impair

performance or cause sedation. Ondansetron does not alter plasma prolactin concentrations.

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.

The clinical safety of ondansetron in children under 2 years has not been established. Increased

incidence of mortality with no specific target organ toxicity has been observed in young rats with

immature drug metabolising enzymes.

Clinical trials

Chemotherapy and Radiotherapy Induced Nausea and Vomiting

Adult studies

Highly emetogenic chemotherapy:

In a double-blind, randomised study, 152 patients were given

ondansetron 8 mg intravenously as a single dose and 173 patients were given 32 mg intravenously as a

single dose 30 minutes prior to cisplatin (greater than or equal to 50 mg/m

). No significant difference

in terms of emesis control or grade of nausea was demonstrated between 8 mg or 32 mg. However, in

some studies conducted in patients receiving medium (50 to 90 mg/m

) or high doses (greater than or

equal to 100 mg/m

) of cisplatin chemotherapy, the 32 mg single dose has demonstrated a statistically

significant superiority over the 8 mg single dose with regard to control of emesis.

In a double-blind, randomised, crossover trial, 103 chemotherapy naive patients scheduled to receive

cisplatin (50 to 120 mg/m

) chemotherapy were recruited. 91 patients completed both courses of

ondansetron 0.15 mg/kg (8 mg) intravenously (three doses) with or without dexamethasone 20 mg

intravenously. The combination of ondansetron and dexamethasone was shown to be significantly

superior to ondansetron alone.

In a randomised, double-blind parallel group study, 420 patients were randomised to receive either an

ondansetron 16 mg suppository prior to cisplatin chemotherapy (greater than or equal to 50 mg/m

) on

day 1 followed by an ondansetron 16 mg suppository once daily for a further two days, or ondansetron

8 mg intravenously prior to cisplatin chemotherapy followed by ondansetron 8 mg orally twice daily

for a further two days. Results from the primary efficacy analysis (i.e. less than or equal to two emetic

episodes on day 1) show that an ondansetron suppository and combined ondansetron intravenous and

oral regimens are equivalent. However, results from the secondary efficacy analyses (e.g. number of

emetic episodes on day 1, the worst day of days 1 to 3 and overall of days 1 to 3) showed that the

ondansetron suppository was less effective. Patients on a combined ondansetron intravenous and oral

regimen

remained

free

emesis

significantly

longer

than

patients

receiving

ondansetron

suppository.

In a randomised, double-blind, parallel group study, 542 patients were randomised to receive either

ondansetron tablets (3 × 8 mg) plus dexamethasone capsules (2 × 6 mg), or intravenous ondansetron

8 mg plus intravenous dexamethasone 20 mg, prior to cisplatin infusion. Ondansetron 24 mg

administered orally was as effective as ondansetron 8 mg given intravenously in controlling acute

emesis and nausea induced by cisplatin chemotherapy.

There are no studies on the use of suppositories in radiation induced nausea and vomiting.

Emetogenic chemotherapy:

In a double-blind, parallel group study, 82 patients were randomised to

either ondansetron 8 mg intravenously prior to cyclophosphamide (greater than or equal to 500 mg/m

based chemotherapy (doxorubicin or epirubicin greater than or equal to 40 mg/m

) followed by 8 mg

orally three times a day for three to five days or metoclopramide 60 mg intravenously prior to

chemotherapy followed by 20 mg orally three times a day for three to five days. Ondansetron was shown

Page 11 of 14

to be significantly superior to metoclopramide.

In a randomised, single-blind study, ondansetron 8 mg orally twice daily in 155 patients was compared

with ondansetron 8 mg orally three times daily in 153 patients for three to five days following

chemotherapy. Ondansetron 8 mg intravenously was given prior to cyclophosphamide (greater than or

equal to 500 mg/m

) based chemotherapy (doxorubicin or epirubicin greater than 40 mg/m

) on day 1.

Ondansetron 8 mg given orally twice daily was as effective as ondansetron 8 mg given orally three

times daily.

In a randomised, double-blind, parallel group study, 406 patients were randomised to receive either an

ondansetron 16 mg suppository once daily for three days or ondansetron 8 mg orally twice daily for

three days. The first administration of the suppository and tablet began two hours and one to two hours

respectively prior to cyclophosphamide chemotherapy (greater than or equal to 500 mg/m

) on day 1.

Results from the primary efficacy analysis (less than or equal to two emetic episodes on the worst day

of days 1 to 3) show that the ondansetron suppository treatment is equivalent to the ondansetron oral

treatment. The ondansetron suppository was less effective than ondansetron oral treatment for a number

of other secondary efficacy criteria (complete control of emesis on the worst day of days 1 to 3, total

number of emetic episodes days 1 to 3 and number of emetic episodes on worst day of days 1 to 3).

Paediatric studies

Three open-label, uncontrolled, non-comparative studies have been performed with 182 patients aged

4 to 18 years with cancer who were given a variety of cisplatin or non-cisplatin regimens. In these trials,

an initial intravenous dose of ondansetron was followed by oral administration of ondansetron. In these

studies, 58% of the 170 evaluable patients had no emetic episodes on day 1.

Post-Operative Nausea and Vomiting (PONV)

Prevention of PONV

Adult studies*:

Surgical patients received ondansetron immediately before the induction of general

balanced anaesthesia. In a double-blind, placebo-controlled study, ondansetron 4 mg intravenously

given to 136 patients immediately prior to general anaesthesia was significantly more effective than

placebo.

In a double-blind, placebo-controlled study, 207 patients were given a single oral dose of ondansetron

16 mg and 204 patients were given placebo one hour prior to induction of anaesthesia. A significantly

greater proportion of surgical patients had no emesis during the 0 to 24 hour post-recovery period

compared with placebo.

*The majority of patients included in the prevention of PONV studies using ondansetron have been

adult women receiving balanced anaesthesia for gynaecological surgery.

Paediatric studies:

Three large, double-blind, placebo-controlled studies have been performed in 1,049

male and female patients (2 to 12 years of age) undergoing general anaesthesia with nitrous oxide. The

surgical procedures included tonsillectomy with or without adenoidectomy, strabismus surgery,

herniorrhaphy, and orchidopexy. Patients were randomised to either single intravenous doses of

ondansetron (0.1 mg/kg for children weighing 40 kg or less, a single 4 mg dose for children weighing

more than 40 kg) or placebo. Study drug was administered over at least 30 seconds, immediately prior

to or following anaesthesia induction. Ondansetron showed significant statistical superiority over

placebo in preventing post-operative nausea and vomiting. Repeat dosing was not undertaken in these

studies. Children at greater risk of post-operative nausea and vomiting are more likely to benefit from

prophylaxis; this includes children with a history of motion sickness or previous post-operative nausea

and vomiting. No comparisons with other drugs for the prevention of nausea and/or vomiting are

available.

Treatment of PONV

Adults studies*:

221 adult surgical patients receiving general balanced anaesthesia, who received no

prophylactic

antiemetics

experienced

nausea

and/or

vomiting

within

hours

post-

Page 12 of 14

operatively, were evaluated in a double-blind study. Patients who experienced an episode of post-

operative nausea and/or vomiting were given ondansetron 4 mg intravenously over two to five minutes,

and this was significantly more effective than placebo.

*The majority of patients treated for PONV in studies using ondansetron have been adult women

receiving balanced anaesthesia for gynaecological surgery.

Paediatric studies:

One large, double-blind, placebo-controlled study was performed in 351 male and

female outpatients (2 to 12 years of age) who received general anaesthesia with nitrous oxide and no

prophylactic antiemetics. Surgical procedures were restricted. Patients who experienced two or more

emetic episodes within two hours following discontinuation of nitrous oxide were randomised to a

single intravenous dose (0.1 mg/kg for children weighing 40 kg or less, a single 4 mg dose for children

weighing more than 40 kg) or placebo administered over at least 30 seconds. Ondansetron demonstrated

statistically significant superiority over placebo in preventing further episodes of nausea and vomiting.

Repeat dosing was not a feature of this study. No data involving comparisons with active treatments

have been evaluated.

5.2

P

HARMACOKINETIC PROPERTIES

Distribution

The terminal elimination half-life of ondansetron after intravenous dosing is 2.5 to 6.1 hours. The half-

life may be prolonged in the elderly. Extent of absorption following intramuscular injection into a lateral

compartment of the thigh is identical to intravenous injection and absorption is rapid with T

occurring

approximately ten minutes after administration. The C

after intramuscular administration is 61%

lower than that following intravenous administration. In patients with severe hepatic impairment,

systemic clearance is markedly reduced with prolonged elimination half-lives (15 to 32 hours).

Metabolism and excretion

Ondansetron is extensively metabolised in humans, with approximately 5% of a radiolabelled dose

recovered as the parent compound from the urine. The primary metabolic pathway is hydroxylation on

the indole ring followed by glucuronide or sulfate conjugation. Although some nonconjugated

metabolites have pharmacological activity, these are not found in plasma concentrations likely to

significantly contribute to the biological activity of ondansetron. Ondansetron is a substrate for multiple

human

hepatic

cytochrome

P-450

enzymes

including

CYP1A2,

CYP2D6

CYP3A4.

This

multiplicity of metabolic enzymes capable of metabolising ondansetron means that inhibition or loss of

one enzyme (e.g. CYP2D6 genetic deficiency) results in little change in overall rates of ondansetron

elimination.

The plasma protein binding is 70 to 76%. The volume of distribution is 1.8 L/kg.

In a study of 21 children aged 3 to 12 years receiving elective surgery with general anaesthesia, the

clearance and volume of distribution of ondansetron following a single intravenous dose of 2 mg (3 to

7 years old) or 4 mg (8 to 12 years old) were reduced. The size of the change was age-related with

clearance falling from about 300 mL/minute at 12 years of age to 100 mL/minute at 3 years. Volume of

distribution fell from about 75 L at 12 years to 17 L at 3 years.

5.3

P

RECLINICAL SAFETY DATA

Genotoxicity

Ondansetron did not induce mutations in Salmonella typhimurium, Escherichia coli or Chinese Hamster

Ovary cells in the presence or absence of metabolic activation, and showed no potential for causing

chromosomal damage

in vitro

in peripheral human lymphocytes or

in vivo

in a mouse micronucleus

assay. No evidence for DNA damage was observed with ondansetron in a yeast mitotic gene conversion

assay.

Carcinogenicity

No evidence for carcinogenic activity was found in two year studies at ondansetron doses up to

Page 13 of 14

10 mg/kg/day by gavage in rats or up to 30 mg/kg/day via drinking water in mice.

6

PHARMACEUTICAL PARTICULARS

6.1

L

IST OF EXCIPIENTS

Sodium chloride

Sodium citrate dihydrate

Citric acid monohydrate

Hydrochloric acid

Sodium hydroxide

Water for injections

6.2

I

NCOMPATIBILITIES

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3

S

HELF LIFE

In Australia, information on the shelf life can be found on the public summary of the Australian Register

of Therapeutic Goods (ARTG).

6.4

S

PECIAL PRECAUTIONS FOR STORAGE

Store below 25°C. Protect from light.

6.5

N

ATURE AND CONTENTS OF CONTAINER

Ondansetron Accord injection 4 mg/2 mL and 8 mg/4 mL is supplied in clear or amber glass ampoules

(Type-I) or amber glass syringes (Type-I).

Ondansetron Accord Injection, 4 mg/2 mL

: Ampoules or syringes each containing 4 mg ondansetron

(as hydrochloride dihydrate) in 2 mL aqueous solution for intramuscular or intravenous administration

in packs of five and ten ampoules or a pack of one syringe.

Ondansetron Accord Injection, 8 mg/4 mL

: Ampoules or syringes each containing 8 mg ondansetron

(as hydrochloride dihydrate) in 4 mL aqueous solution for intravenous administration in packs of five

and ten ampoules or a pack of one syringe.

6.6

S

PECIAL PRECAUTIONS FOR DISPOSAL

In Australia, any unused medicine or waste material should be disposed of in accordance with local

requirements.

6.7

P

HYSICOCHEMICAL PROPERTIES

Ondansetron hydrochloride dihydrate is a white or almost white powder with a melting point of 173

It is sparingly soluble in water and in ethanol, soluble in methanol and slightly soluble in methylene

chloride. The pKa of ondansetron hydrochloride dihydrate is 7.4. The partition coefficient, log P in n-

octanol: water is 2.14.

Chemical Name:

1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-

one, hydrochloride dihydrate

Molecular Formula:

O.HCl.2H

Molecular Weight:

365.9

Page 14 of 14

Chemical structure

CAS number

99614-01-4 (ondansetron hydrochloride dihydrate), 99614-02-5 (ondansetron)

7

MEDICINE SCHEDULE (POISONS STANDARD)

S4 - Prescription Only Medicine

8

SPONSOR

Accord Healthcare Pty Ltd

Level 24, 570 Bourke Street

Melbourne, VIC, 3000

Australia

www.accord-healthcare.com.au

9

DATE OF FIRST APPROVAL

17 April 2014

10

DATE OF REVISION

09 April 2021

Version 7.0

Summary table of changes

Section

Changed

Summary of new information

4.6

Updated pregnancy information

4.9

Added ECG monitoring recommendation

Various

Editorial updates

Read the complete document

Public Summary

Summary for ARTG Entry:

338224

ONDANSETRON ACCORD ondansetron (as hydrochloride dihydrate) 4 mg/2 mL solution for injection

pre-filled syringe

ARTG entry for

Medicine Registered

Sponsor

Accord Healthcare Pty Ltd

Postal Address

Level 24 570 Bourke Street, Melbourne, VIC, 3000

Australia

ARTG Start Date

9/11/2020

Product Category

Medicine

Status

Active

Approval Area

Drug Safety Evaluation Branch

Conditions

Conditions applicable to all therapeutic goods as specified in the document "Standard Conditions Applying to Registered or Listed Therapeutic Goods Under

Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Standard Conditions Applying to Registered or

Listed Therapeutic Goods Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Products

1 . ONDANSETRON ACCORD ondansetron (as hydrochloride dihydrate) 4 mg/2 mL solution for injection

pre-filled syringe

Product Type

Single Medicine Product

Effective Date

9/11/2020

Permitted Indications

No Permitted Indications included on Record

Indication Requirements

No Indication Requirements included on Record

Standard Indications

No Standard Indications included on Record

Specific Indications

Ondansetron injection is indicated

? For the prevention and treatment of nausea and vomiting induced by cytotoxic therapy and radiotherapy.

? For the prevention and treatment of post-operative nausea and vomiting.

Warnings

See Product Information and Consumer Medicine Information for this product

Additional Product information

Container information

Type

Material

Life Time

Temperature

Closure

Conditions

Syringe

Glass Type I Coloured 24 Months

Store below 25

degrees Celsius

Neither child resistant

closure nor restricted

flow insert

Protect from Light

Pack Size/Poison information

Pack Size

Poison Schedule

Pack of 1 pre-filled syringe

(S4) Prescription Only Medicine

Components

1 . ONDANSETRON ACCORD ondansetron (as hydrochloride dihydrate) 4 mg/2 mL solution for injection pre-filled syringe

Dosage Form

Injection, solution

Route of Administration

Intramuscular

Intravenous

Visual Identification

Clear, colourless solution in an amber glass pre-filled syringe

Active Ingredients

Public Summary

Page 1 of

Produced at 12.01.2021 at 07:26:54 AEDT

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

ondansetron hydrochloride dihydrate

4.99 mg

Equivalent: ondansetron

4 mg

Other Ingredients (Excipients)

citric acid monohydrate

hydrochloric acid

sodium chloride

sodium citrate dihydrate

sodium hydroxide

water for injections

© Commonwealth of Australia. This work is copyright. You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

written approval from the Commonwealth. Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summary

Page 2 of

Produced at 12.01.2021 at 07:26:54 AEDT

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

Similar products

Search alerts related to this product

View documents history

Share this information