SUMMARY CMI

GRANISETRON KABI

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I being given GRANISETRON KABI?

GRANISETRON KABI contains the active ingredient granisetron. GRANISETRON KABI is used to prevent nausea (feeling sick) and vomiting. It is especially useful when you need to have medical treatment that may cause you to feel or be sick, for example, chemotherapy, radiotherapy or surgery.

For more information, see Section 1. Why am I being given GRANISETRON KABI? in the full CMI.

2. What should I know before I am given GRANISETRON KABI?

Do not use if you have ever had an allergic reaction to GRANISETRON KABI or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given GRANISETRON KABI? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with GRANISETRON KABI and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is GRANISETRON KABI given?

Your doctor will decide how much GRANISETRON KABI you should receive and for how long you should receive it.

More instructions can be found in Section 4. How is GRANISETRON KABI given? in the full CMI.

5. What should I know while receiving GRANISETRON KABI?

For more information, see Section 5. What should I know while receiving GRANISETRON KABI? in the full CMI.

6. Are there any side effects?

Less serious side effects: related to nervous system (headache, unusual tiredness or weakness, dizziness or light-headedness, agitation, nervousness, drowsiness, difficulty in sleeping), gastrointestinal (abdominal pain, constipation, diarrhoea) and other (altered taste, fever, skin rash). Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects: related to heart (chest pain, changes in your heartbeat, severe dizziness or fainting), nervous system (seizures), serotonin syndrome (fever, sweating, fast heartbeat, agitation or confusion, loss of muscle coordination, possibly loss of consciousness) and allergic reaction (shortness of breath, wheezing or difficulty breathing, swelling of the face/lips/tongue or other parts of the body, rash, itching or hives on the skin). Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

GRANISETRON KABI

Active ingredient: granisetron hydrochloride

Consumer Medicine Information (CMI)

This leaflet provides important information about using GRANISETRON KABI. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using GRANISETRON KABI.

Where to find information in this leaflet:

1. Why am I being given GRANISETRON KABI?
2. What should I know before I am given GRANISETRON KABI?
3. What if I am taking other medicines?
4. How is GRANISETRON KABI given?
5. What should I know while receving GRANISETRON KABI?
6. Are there any side effects?
7. Product details

1. Why am I being given GRANISETRON KABI?

GRANISETRON KABI contains the active ingredient Granisetron (as granisetron hydrochloride). GRANISETRON KABI belongs to a group of medicines called anti-emetics.

GRANISETRON KABI is used to prevent nausea (feeling sick) and vomiting. It is especially useful when you need to have medical treatment that may cause you to feel or be sick, for example, chemotherapy, radiotherapy or surgery.

Your doctor may have prescribed GRANISETRON KABI for another reason. Ask your doctor if you have any questions about why GRANISETRON KABI has been prescribed for you.

GRANISETRON KABI is available only with a doctor's prescription.

GRANISETRON KABI is not addictive.

2. What should I know before I am given GRANISETRON KABI?

Warnings

Do not use GRANISETRON KABI if:

• you are allergic to granisetron, or any of the ingredients listed at the end of this leaflet.

Always check the ingredients to make sure you can use this medicine.

Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing, swelling of the face/lips/tongue or other parts of the body, rash, itching or hives on the skin.

Check with your doctor if you:

• have any other medical conditions:
  - a heart condition related to changes in the rhythm or rate of your heartbeat
• take any medicines for any other condition
• have allergies to any other medicines, foods, dyes or preservatives
• have had an allergic reaction with other medicines used to prevent nausea and vomiting, such as ondansetron and tropisetron; you may have an allergic reaction to GRANISETRON KABI as well
• have been given GRANISETRON KABI before, and you became unwell; you may need to be given another medicine instead
• have severe constipation.

If you have not told your doctor about any of the above, tell your doctor before you are given GRANISETRON KABI. During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. Your doctor will discuss with you the risks and benefits of receiving GRANISETRON KABI while you are pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Your doctor can discuss with you the risks and benefits of receiving GRANISETRON KABI while you are breastfeeding.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with GRANISETRON KABI and affect how it works.

Medicines that may affect the way GRANISETRON KABI works include:

• Phenobarbitone – a medicine used to treat epilepsy. Phenobarbitone may be affected by GRANISETRON KABI or may affect how well GRANISETRON KABI works. You may need different amounts of your medicine, or you may need to take a different medicine.
• Medicines that can affect the serotonin levels in your body; these may include:
  - some antibiotics
  - medicines used to treat depression
  - medicines that treat or prevent pain
  - some medicines to treat Parkinson's disease
  - medicines to treat obesity
  - medicines used to treat attention hyperactivity disorder.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect GRANISETRON KABI.

4. How is GRANISETRON KABI given?

How much is given

Your doctor will decide how much GRANISETRON KABI you will receive and for how long you will receive it, this depends on your condition and other factors such as your weight.

How GRANISETRON KABI is given to you

GRANISETRON KABI will only be given to you by a doctor or a nurse.

GRANISETRON KABI will be diluted with a suitable infusion before it is administered to you as a fast or slow single dose injection into a vein (intravenous ‘drip’).

If you are given too much

Since GRANISETRON KABI is given to you in hospital by a doctor or a nurse, it is very unlikely that you will be given too large a dose.

However, if you think that you have received too much GRANISETRON KABI and you experience severe side effects, tell your doctor immediately.

Symptoms of an overdose may include the side effects listed below in the ‘Side effects’ section but are usually of a more severe nature. Ask your doctor or pharmacist if you have any concerns.

5. What should I know while receiving GRANISETRON KABI?

Things you should do

Keep all of your doctor's appointments, so that your progress can be checked.

Call your doctor straight away if you:

• become pregnant while being given GRANISETRON KABI

Remind any doctor, dentist or pharmacist who treat you that you are receiving GRANISETRON KABI.

Things you should not do

• Do not take any other medicines whether they require a prescription or not without first telling your doctor.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how GRANISETRON KABI affects you.

GRANISETRON KABI may cause dizziness or drowsiness in some people.

Drinking alcohol

Tell your doctor if you drink alcohol.

If you drink alcohol, dizziness or drowsiness may be worse. Your doctor may suggest that you avoid alcohol or reduce the amount of alcohol you drink while you are being given GRANISETRON KABI.

Looking after your medicine

• GRANISETRON KABI is stored by hospital staff in the pharmacy or in the ward
• This medicine is kept below 25°C and protected from light.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/safety/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What GRANISETRON KABI contains

Do not take this medicine if you are allergic to any of these ingredients.

What GRANISETRON KABI looks like

GRANISETRON KABI is a clear solution with no visible particles.

GRANISETRON KABI 1 mg/mL (AUST R 159273)

Pack size: 1, 5 and 10 ampoules per carton.

GRANISETRON KABI 3 mg/3 mL (AUST R 159274)

Pack size: 1, 5 and 10 ampoules per carton.

Who distributes GRANISETRON KABI

Fresenius Kabi Australia Pty Limited
Level 2, 2 Woodland Way
Mount Kuring-gai NSW 2080
Australia
Telephone: (02) 9391 5555

This leaflet was prepared in April 2023.

Published by MIMS July 2023

1 Name of Medicine

Granisetron hydrochloride.

2 Qualitative and Quantitative Composition

Granisetron hydrochloride is a white to off-white crystalline powder which is freely soluble in water and sodium chloride 0.9% at 20°C.
Granisetron Kabi Concentrated Injection contains granisetron hydrochloride equivalent to granisetron free base 1 mg/mL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Concentrated Injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Prevention and treatment of nausea and vomiting induced by cytotoxic chemotherapy in adults and children.
Prevention of nausea and vomiting induced by radiotherapy in adults only.
Prevention and treatment of post-operative nausea and vomiting in adults only.

4.2 Dose and Method of Administration

Granisetron Kabi is for intravenous administration only.

Chemotherapy induced nausea and vomiting.

Adults.

Children.

Radiotherapy induced nausea and vomiting.

Adults.

Post-operative nausea and vomiting.

Prevention of post-operative nausea and vomiting in adults.

Treatment of established post-operative nausea and vomiting in adults.

Special dosage instructions.

Combination with a corticosteroid.

Preparation and administration.

4.3 Contraindications

Hypersensitivity to the active substance granisetron hydrochloride, or to any of the excipients in Granisetron Kabi.

4.4 Special Warnings and Precautions for Use

As granisetron may reduce lower bowel motility, patients with signs of sub-acute intestinal obstruction should be monitored following administration of Granisetron Kabi.
As for other 5-HT₃ antagonists, cases of ECG modifications including QT prolongation have been reported with granisetron. The ECG changes with granisetron were minor, generally not of clinical significance and specifically, there was no evidence of proarrhythmia. However, in patients with pre-existing arrhythmias or cardiac conduction disorders, this might lead to clinical consequences. Therefore, caution should be exercised in patients with cardiac co-morbidities, on cardio-toxic chemotherapy and/or with concomitant electrolyte abnormalities.
In healthy subjects, no clinically relevant effects on resting EEG or on the performance of psychometric tests were observed after IV granisetron at any dose tested (up to 200 microgram/kg).
Cross-sensitivity between 5-HT3 antagonists has been reported.
As with other 5-HT₃ antagonists, cases of serotonin syndrome (including altered mental status, autonomic dysfunction and neuromuscular abnormalities) have been reported following the concomitant use of granisetron and other serotonergic drugs. If concomitant treatment with granisetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in renal impairment.

Use in hepatic impairment.

Use in the elderly.

Paediatric use.

Effects in laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Granisetron does not induce or inhibit the cytochrome P₄₅₀ drug metabolising enzyme system in rodent studies. In humans, hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of intravenous granisetron of approximately one-quarter.
In healthy human subjects, granisetron has been safely administered with benzodiazepines, neuroleptics, and anti-ulcer medications commonly prescribed with anti-emetic treatments. Additionally, granisetron has shown no apparent drug interaction with emetogenic cancer chemotherapies.
No specific interaction studies have been conducted in anaesthetised patients, but granisetron injections have been safely administered with commonly used anaesthetic and analgesic agents. In addition, in vitro human microsomal studies have shown that the cytochrome P₄₅₀ subfamily 3A4 (involved in the metabolism of some of the main narcotic analgesic agents) is not modified by granisetron.
As for other 5-HT₃ antagonists, cases of ECG modifications including QT prolongation have been reported with granisetron. The ECG changes with granisetron were minor, generally not of clinical significance and specifically, there was no evidence of proarrhythmia. However, in patients concurrently treated with drugs known to prolong QT interval and/or are arrhythmogenic, this may lead to clinical consequences.
As with other 5-HT₃ antagonists, cases of serotonin syndrome (including altered mental status, autonomic dysfunction and neuromuscular abnormalities) have been reported following the concomitant use of granisetron and other serotonergic drugs. If concomitant treatment with granisetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

(Category B1)
There is no experience of granisetron in human pregnancy. Animal studies have shown no teratogenic effects in rats or rabbits at intravenous doses up to 9 and 3 mg/kg/day respectively. Time weighted systemic exposure (maternal plasma AUC) at the highest intravenous dose in rats was about 7 times higher than that in humans at therapeutic dose levels, but insufficient data are available for a similar comparison in rabbits. Because of the low safety margin indicated by the animal studies and because animal reproduction studies are not always predictive of human response, granisetron should be used during pregnancy only if clearly needed.
A study in lactating rats showed that the rate of excretion in milk after IV dosing is less than 1% of the dose per hour, and that at least some of this is absorbed by the offspring.
There are no data on the excretion of granisetron in human breast milk, therefore use of the drug during lactation should be limited to situations where the potential benefit to the mother justifies the potential risk to the nursing infant.

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

There are no data on the effect of granisetron on the ability to drive, however there have been occasional reports of somnolence in clinical studies which should be taken into account.

4.8 Adverse Effects (Undesirable Effects)

Granisetron has been well tolerated in human studies. The most frequently reported adverse reactions for granisetron are headache and constipation which may be transient. ECD changes including QT prolongation have been reported with granisetron (see Section 4.4 Special Warnings and Precautions for Use).
As with other 5-HT₃ antagonists, cases of serotonin syndrome (including altered mental status, autonomic dysfunction and neuromuscular abnormalities) have been reported following the concomitant use of granisetron and other serotonergic drugs. If concomitant treatment with granisetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Table 1 gives the comparative frequencies of the five commonly reported adverse events (> 3%) in patients receiving granisetron injection, 40 microgram/kg, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24-hour period following granisetron injection administration.
In the absence of a placebo group, there is uncertainty as to how many of these events should be attributed to granisetron, except for headache, which was clearly more frequent than in comparison groups.
Adverse events reported in clinical trials other than those in Table 1 are listed below. All adverse experiences are included in the list except those reported in terms so general as to be uninformative and those experiences for which the drug cause was remote. It should however be noted that causality has not necessarily been established.
Events are listed within body systems and categorised by frequency according to the following definitions: very common events reported at a frequency of greater or equal to 1/10 patients; common events reported at a frequency of greater or equal to 1/100 patients; uncommon events reported at a frequency of less than 1/100 but greater or equal to 1/1,000 patients; rare events reported at a frequency of less than 1/1,000 patients.

Body as a whole.

Cardiovascular.

Hypersensitivity.

Gastrointestinal disorders.

Hepatic.

Nervous system.

Dermatological.

Special senses.

Reporting of suspected adverse reactions.

4.9 Overdose

There is no specific antidote for Granisetron Kabi. In the case of overdosage, symptomatic treatment should be given. Overdose with the intravenous formulation has occurred. Overdosage of up to 38.5 mg of granisetron as a single injection has been reported without symptoms or only the occurrence of a slight headache.
For information on the management of overdose, contact the Poisons Information Centre on 131126.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

Cisplatin based chemotherapy.

Moderately emetogenic chemotherapy.

Prevention.

Treatment.

5.2 Pharmacokinetic Properties

A linear pharmacokinetic relationship was found after IV administration up to 4-fold the recommended dose.

Distribution.

Metabolism.

Excretion.

Pharmacokinetics in special populations.

Elderly.

Renal impairment.

Hepatic impairment.

5.3 Preclinical Safety Data

Carcinogenicity.

Genotoxicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Contains: sodium chloride, citric acid monohydrate, hydrochloric acid, sodium hydroxide and water for injections.

6.2 Incompatibilities

Granisetron Kabi is a concentrated solution for infusion intended for dilution with Sodium Chloride 0.9% Injection, Glucose 5% Injection or Lactated Ringer's Solution prior to intravenous infusion. It is a clear, colourless solution free of visible particles.
Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

The expiry date (month/year) is stated on the package after the word EXP.
To reduce microbiological hazard, use as soon as possible after dilution. If storage is necessary after dilution, hold at 2°C to 8°C for not more than 24 hours.

6.4 Special Precautions for Storage

Store the ampoules in the original carton below 25°C. Protect from light. Do not freeze. Single use only. Discard unused portion.

6.5 Nature and Contents of Container

Granisetron Kabi is available in packs of 1, 5 and 10 ampoules in the following presentations:
Granisetron Kabi 1 mg/1 mL: AUST R 159273.
Granisetron Kabi 3 mg/3 mL: AUST R 159274.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes