Section 4.9 updated to include information on paediatric population.

Change of Marketing Authorisation Holder.

Section 4.1 . Clarification to SmPC 4.1 Indications on paediatric treatment to separate adult and paediatric indications and to give age ranges for paediatric indications.
Section 4.2. Addition of ‘IV’ to Table 2 for consistency with Table 1.
Section 4.8. Update to include toxic skin eruption, including toxic epidermal necrolyis as an Undesirable Effect.
Section 4.8 Update to provide clarification on the setting of dizziness, and existing Undesirable Effect.
Section 5.2. Clarification on dosing recommendations for elderly.

Section 4.9 – Information added to the 'Symptoms and Signs and Treatment' sections of the Overdose section

Update to MA holder address change

4.2 addition of dosing regime (spoonful)

4.8 addition of how to report an adverse event

Changes to:

Section 4.2 - Posology and method of administration,
Section 4.3 - Contraindications,
Section 4.4 - Special warnings and precautions for use,
Section 4.5 - Interaction with other medicinal products and other forms of interaction,
Section 4.9 - Overdose,
Section 5.1 - Pharmacodynamic properties,
Section 5.2 - Pharmacokinetic properties,
Section 5.3 - Preclinical safety data

 

 

4.2       Posology and Method of Administration

 

CHEMOTHERAPY AND RADIOTHERAPY INDUCED NAUSEA AND VOMITING (CINV and RINV)

Emetogenic Chemotherapy and Radiotherapy:-

The recommended intravenous or intramuscular dose of Zofran is 8mg administered as a slow injection in not less than 30 seconds immediately before treatment.

 

Highly Emetogenic Chemotherapy:-

For patients receiving highly emetogenic chemotherapy, e.g. high-dose cisplatin.  Zofran may be administered as a single 8mg intravenous or intramuscular dose immediately before chemotherapy. Doses of greater than 8mg and up to maximum of 3216mg of Zofran may only be given by intravenous infusion diluted in 50-100ml of saline or other compatible infusion fluid (see Section 6.6 Compatibility with Intravenous FluidsPharmaceutical Precautions) and infused over not less than 15 minutes. A single dose greater than 16mg 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 emetogenic chemotherapy,Alternatively a dose of 8mg of Zofran may be administered by slow intravenous injection or intramuscular injectionin not less than 30 seconds, or intramuscular injection immediately before chemotherapy, followed by two further intravenous or intramuscular doses of 8mg two to four hours apart, or by a constant infusion of 1mg/hour for up to 24 hours.

 

4.4       Special Warnings and Precautions for Use

Rarely, transient ECG changes including QT interval prolongation have been reported in patients receiving ondansetron. In addition, post-marketing cases of Torsades de Pointes have been reported in patients using ondansetron. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc. These conditions include patients with electrolyte abnormalities, with congenital long QT syndrome, or patients taking other medicinal products that lead to QT prolongation.

 

Ondansetron prolongs the QT interval in a dose-dependent manner (see Section 5.1 Pharmacodynamic Properties).  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. 

4.5       Interaction with other medicinal products and other forms of interactions

 

Caution should be exercised when ondansetron is coadministered with drugs that prolong the QT interval and/or cause electrolyte abnormalities (see Section 4.4 Special Warnings and Precautions for Use).

 

Pregnancy

The safety of Zofran 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 Zofran 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 Zofran should not breast-feed their babies.

 

4.9       Overdose

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

 

 

5.         PHARMACOLOGICAL PROPERTIES

 

5.1              Pharmacodynamic Properties

 

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 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 baseline-correction 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 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.

 

5.3       Preclinical Safety Data

 

            A study in cloned human cardiac ion channels has shown ondansetron has the potential to affect cardiac repolarisation via blockade of hERG potassium channels at clinically relevant concentrations. In vivo, a lengthening of the QT interval has been observed in anaesthetised cats following IV dosing, but at doses exceeding 100 times those effective pharmacologically. Similar effects were not seen in cynomolgus monkeys. Transient ECG changes have been reported in the clinic (see Warnings and Precautions). Dose-dependent QT prolongation has been observed in a thorough QT study in human volunteers (see Section 5.1 Pharmacodynamic Properties – QT prolongation).

 

 

6.6       Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

 

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 1632mg of ondansetron diluted in 50-100ml of the following infusion fluids:

 

 

Change to:

Section 4.3 - Contraindications,
Section 4.4 - Special warnings and precautions for use,
Section 4.5 - Interaction with other medicinal products and other forms of interaction,

Section 4.8 - Undesirable effects

Changes to the following:

·         Section 2

·         Section 4.2

·         Section 4.4

·         Section 4.7

·         Section 4.8

·         Section 5.1

·         Section 5.2

·         Section 5.3

·         Section 6.6

 



1.         NAME OF THE MEDICINAL PRODUCT

 

Zofran 8mg/4ml Solution for Injection or Infusion

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each ml contains 2mg ondansetron as hydrochloride dihydrate (8mg/4ml).

 

For a full list of eExcipients see Section 6.1

 

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4.         CLINICAL PARTICULARS

 

4.2       Posology and Method of Administration

 

Zofran is also available for oral use to allow the route of administration and dosing to be flexible.

 

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 dose range of Zofran Solution for Injection or Infusion is 8 to 32 mg a day and selected as shown below:-

 

Emetogenic Chemotherapy and Radiotherapy:-

The recommended intravenous or intramuscular dose of Zofran is 8mg administered as a slow injection immediately before treatment.

 

Oral treatment is recommended to protect against delayed or prolonged emesis after the first 24 hours. The recommended oral dose is 8 mg to be taken twice daily.

 

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POST-OPERATIVE NAUSEA AND VOMITING

 

 

Children and Adolescents (aged 1 month to 17 years):-

For prevention and treatment of post-operative nausea and vomiting in paediatric patients having surgery performed under general anaesthesia, Zofran may be administered by slow intravenous injection at a dose of 0.1mg/kg up to a maximum of 4mg either prior to, at or after induction of anaesthesia.

 

For treatment of established post-operative nausea and vomiting in paediatric patients, Zofran may be administered by slow intravenous injection at a dose of 0.1 mg/kg up to a maximum of 4mg., or after surgery

 

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4.5       Interaction with Other medicinal productsMedicaments and Other Forms of Interaction

 

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4.6       Fertility, Pregnancy and Lactation

 

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6.         PHARMACEUTICAL PARTICULARS

 

 

6.2       Incompatibilities

 

Zofran Solution for Injection or Infusion should not be administered in the same syringe or infusion as any other medication (see Section 6.6 Instructions for Use and Handling).

 

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

Zofran Solution for Injection or Infusion should only be admixed with those infusion solutions which are recommended (see Section 6.6 Instructions for Use and Handling).

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6.3       Shelf life

 

Unopened Zofran Solution for Injection or Infusion ampoules have a shelf life of 3 years.

Once opened Zofran Solution for Injection or Infusion has a shelf life of 24 hours when stored at refrigeration temperatures of 2-8°C only.

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6.4       Special Precautions for Storage

 

Do not store above 30°C.  Store in the original container.

 

Pharmaceutical precautions:  In the interest of good microbiological practice storage of reconstituted or diluted injection solutions is not recommended unless the product is aseptically prepared and even then must not exceed 24 hours at refrigeration temperatures of 2-8°C only.

 

Dilutions of Zofran Solution for Injection or Infusion with compatible intravenous infusion fluids are stable under normal room lighting conditions or daylight for at least 24 hours, thus no protection from light is necessary while infusion takes place.

 

Zofran Solution for Injection or Infusion should not be administered in the same syringe or infusion as any other medication.  Zofran Solution for Injection or Infusion should not be autoclaved.

 

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6.5       Nature and Contents of Container

 

Zofran Solution for Injection or Infusion is supplied in Type I clear glass, One-Point-Cut (OPC) or Snap-Ring ampoule, sealed by fusion of the glass.  Dose volumes of 2ml are presented in 2ml ampoules and dose volumes of 4ml are presented in 5ml ampoules.  The ampoules are packed in plastic ampoule like trays in cardboard boxes, five ampoules per box.

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6.6       Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the productInstructions for Use and Handling

 

            Compatibility with intravenous fluids:-

 

Zofran Solution for Injection or Infusion should only be admixed with those infusion solutions which are recommended.

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7.         MARKETING AUTHORISATION HOLDER

           

            GlaxoSmithKline (Ireland) Limited,

            Stonemasons Way,

Rathfarnham,

Dublin 16

Ireland

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9.         DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

 

            Date of first authorisation: 27^th June 1990

Date of last renewal: /27^th June 20052010

 

 

10.       DATE OF REVISION OF THE TEXT

 

            January 2007 March 2011