Consumer medicine information

GRANISETRON SANDOZ

Granisetron

BRAND INFORMATION

Brand name

Granisetron Sandoz Concentrate for injection

Active ingredient

Granisetron

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using GRANISETRON SANDOZ.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Granisetron Sandoz.

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 this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

WHAT GRANISETRON SANDOZ IS USED FOR

This medicine is used stop nausea (feeling sick) and vomiting which can occur after some treatments such as chemotherapy or radiotherapy.

It contains the active ingredient granisetron. Granisetron belongs to a group of medicines called serotonin 5-HT3 receptor antagonists. It is an anti-emetic.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

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

BEFORE YOU ARE GIVEN GRANISETRON SANDOZ

When you must not be given it

Do not take this medicine if you an allergy to:

  • granisetron, the active ingredient, or to any of the other ingredients listed at the end of this leaflet under Product Description

Some of the 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.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • severe constipation
  • heart condition related to changes in the rhythm or rate of your heart beat.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding.

Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start taking Granisetron Sandoz.

If you are not sure whether you should be given Granisetron Sandoz or have become unwell if previously given Granisetron Sandoz, talk to you doctor as there may be an alternative medicine.

Taking other medicines

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

Some medicines and Granisetron Sandoz may interfere with each other. These include:

  • phenobarbitone, a medicine used to treat epilepsy.

This medicine may be affected by Granisetron Sandoz or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

HOW GRANISETRON SANDOZ IS GIVEN

How much is given

The dose of Granisetron Sandoz you will receive depends on your medical condition and other factors such as your weight.

How it is given

Granisetron Sandoz is usually administered in a hospital as an injection into a vein. It will be given by a doctor or nurse.

If you receive too much (overdose)

Granisetron Sandoz is usually administered in a hospital, under the supervision of a doctor. Therefore it is unlikely that you will receive too much. However, you should tell your doctor or nurse immediately if you feel unwell at all whilst you are being given Granisetron Sandoz. You may need urgent medical attention.

Symptoms of an overdose may include the side effects listed below in the ‘Side Effects’ section but are usually of a more severe nature.

WHILE YOU ARE BEING GIVEN GRANISETRON SANDOZ

Things you must do

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you become pregnant while you are being treated with Granisetron Sandoz, tell your doctor immediately.

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

Things you must not do

Do not take any other medicines without first telling your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how Granisetron Sandoz affects you.

This medicine may cause drowsiness or sleepiness in some people.

Be careful of drinking alcohol while you are being given this medicine.

If you drink alcohol, dizziness or light-headiness may be worse.

SIDE EFFECTS

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being treated with Granisetron Sandoz.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • headache
  • unusual tiredness or light-headedness
  • agitation
  • nervousness
  • drowsiness
  • difficulty in sleeping
  • abdominal pain
  • constipation
  • diarrhoea
  • altered taste
  • fever
  • skin rash.

The above list includes the more common side effects of the medicine.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • chest pain
  • changes in your heart beat
  • severe dizziness or fainting
  • symptoms of an allergic reaction, such as 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.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

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

Other side effects not listed above may also occur in some people.

AFTER USING GRANISETRON SANDOZ

Storage

Granisetron Sandoz will be stored in the pharmacy or on the ward. The ampoules are kept in a cool dry place protected from light where the temperatures stay below 25°C.

PRODUCT DESCRIPTION

What it looks like

Granisetron Sandoz injection is a clear, colourless to slightly yellow solution. It is supplied in packs of 1 and 5 clear glass vials.

Ingredients

Active ingredients:

  • Granisetron Sandoz 3mg/3mL - 3mg granisetron (as granisetron hydrochloride)
  • Granisetron Sandoz 1mg/1mL - 1mg granisetron (as granisetron hydrochloride)

Inactive ingredients:

  • sodium chloride
  • citric acid monohydrate
  • sodium hydroxide
  • hydrochloric acid
  • water for injections.

This medicine does not contain lactose or gluten.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
Level 2, 19 Harris St
Pyrmont NSW 2009
Tel: 1800 634 500

Novartis New Zealand Ltd
Private Bag 65904 Mairangi Bay
Auckland 0754
New Zealand
Tel: 0800 354 335

This leaflet was prepared in October 2011.

Australian Register Numbers
Granisetron Sandoz 3mg/3ml injection: AUST R 173996
Granisetron Sandoz 1mg/1ml injection: AUST R 173995

BRAND INFORMATION

Brand name

Granisetron Sandoz Concentrate for injection

Active ingredient

Granisetron

Schedule

S4

 

Name of the medicine

Granisetron hydrochloride.

Excipients

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

Description

Chemical name:1-methyl-N-[(1R,3r,5S)-9-methyl-9-azabicyclo [3.3.1] non-3-yl]-1H-indazole-3-carboxamide hydrochloride. Chemical formula: C18H24N4O.HCl. CAS: 107007-99-8 (granisetron hydrochloride); 109889-09-0 (granisetron free base). MW: 348.9 (granisetron hydrochloride); 312.4 (granisetron free base). Granisetron hydrochloride is a white or almost white powder, which is freely soluble in water and 0.9% sodium chloride at 20°C.

Pharmacology

Pharmacodynamics.

Granisetron is a potent antiemetic and highly selective antagonist of 5-hydroxytryptamine (5-HT)3 receptors. Radioligand binding studies have demonstrated that granisetron has negligible affinity for other receptor types including 5-HT, α1and α2, β-adrenoreceptors, histamine H1, picrotoxin, benzodiazepine, opioid and dopamine D2 binding sites.
Antagonism of 5-HT3 receptors located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone in the area postrema, is one of the most effective pharmacological methods of preventing cytotoxic induced emesis. Mucosal enterochromaffin cells release serotonin during chemotherapy induced emesis. Serotonin stimulates 5-HT3 receptors and evokes a vagal afferent discharge to subsequently induce emesis. Animal pharmacological studies have shown that in binding to 5-HT3 receptors, granisetron blocks serotonin stimulation, and is effective in alleviating the retching and vomiting evoked by cytostatic treatment. In the ferret animal model, a single granisetron injection prevented vomiting due to high dose cisplatin or arrested vomiting within 5 to 30 seconds.
In healthy subjects, granisetron produced no consistent or clinically important changes in pulse rate, blood pressure or ECG. Granisetron did not affect the plasma levels of prolactin or aldosterone.
Granisetron concentrated injection showed no effect on gut transit time in normal volunteers given single doses up to 200 microgram/kg.

Pharmacokinetics.

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

Distribution.

Granisetron is extensively distributed with a mean volume of distribution of approximately 3 L/kg; plasma protein binding is approximately 65%, and granisetron distributes freely between plasma and red blood cells.

Metabolism.

Granisetron clearance is predominantly via hepatic metabolism and is rapid in most subjects.
Granisetron metabolism involves N-demethylation and aromatic ring oxidation followed by conjugation. Animal studies suggest some metabolites of granisetron may also have 5-HT3 receptor antagonist activity. However, in humans the metabolites are present in very low concentrations and are thought not to contribute to the pharmacological action.

Elimination.

Mean plasma half-life of granisetron in patients is 9 hours with wide intersubject variability.
The plasma concentration of granisetron is not clearly correlated with antiemetic efficacy.
Clinical benefit may be conferred even when granisetron is not detectable in plasma.
Urinary excretion of unchanged granisetron averages 12% of the dose in 48 hours, whilst the remainder is excreted as metabolites; 47% in the urine and 34% in the faeces.

Pharmacokinetics in special populations.

Elderly.

In elderly subjects after single intravenous doses, pharmacokinetic parameters were within the range found for younger healthy volunteers.

Renal impairment.

In patients with severe renal failure, data indicate that pharmacokinetic parameters after a single intravenous dose are generally similar to those in normal subjects.

Hepatic impairment.

In patients with hepatic impairment due to neoplastic liver involvement, total clearance of granisetron was approximately halved compared to patients without hepatic impairment. However, no dosage adjustment is recommended.

Clinical Trials

Intravenous administration.

Single day chemotherapy.

Cisplatin based chemotherapy.

In a double blind, placebo controlled study in 28 patients, granisetron concentrated injection administered as a single intravenous infusion of 40 microgram/kg, was significantly more effective than placebo in preventing nausea and vomiting induced by cisplatin chemotherapy.
Granisetron concentrated injection was also evaluated in a randomised dose response study of cancer patients receiving cisplatin > 75 mg/m2. Additional chemotherapeutic agents included anthracyclines, carboplatin, cytostatic antibiotics, folic acid derivatives, methylhydralazine, nitrogen mustard analogs, podophyllotoxin derivatives, pyrimidine analogs and vinca alkaloids. Granisetron concentrated injection doses of 10 and 40 microgram/kg were superior to 2 microgram/kg in preventing cisplatin induced nausea and vomiting.

Moderately emetogenic chemotherapy.

Granisetron concentrated injection 40 microgram/kg, was compared with the combination of chlorpromazine (50 to 200 mg/24 hours) and dexamethasone (12 mg) in patients treated with moderately emetogenic chemotherapy, including primarily carboplatin > 300 mg/m2, cisplatin 20 to 50 mg/m2and cyclophosphamide > 600 mg/m2. Granisetron concentrated injection was superior to the chlorpromazine/ dexamethasone regimen in preventing nausea and vomiting.

Repeat cycle chemotherapy.

In an uncontrolled trial, 75 cancer patients received granisetron concentrated injection 40 microgram/kg prophylactically, for three cycles of chemotherapy. 31 patients received it for at least four cycles and 8 patients received it for at least six cycles. Granisetron concentrated injection efficacy remained relatively constant over the first six repeat cycles, with complete response rates (no vomiting and no moderate or severe nausea in 24 hours) of 65-70%. No patients were studied for more than 9 cycles.
During the clinical trial program, there were 26 reports of cardiac arrest. Of these, 25 were considered to be unrelated to granisetron administration and were attributed to the underlying disease or concomitant cytostatic medication with time of onset up to 4 months after initiation of therapy.
In the one case where granisetron administration was causally related, the patient experienced cardiac arrest as part of a severe allergic reaction. This event was not related to any direct cardiotoxic effect of granisetron. A full recovery was made on discontinuation of therapy.
Of the 40 reports of renal failure, causality was assigned in 37 cases. All 37 were considered to be unrelated to granisetron administration and were attributed to the underlying disease or cisplatin, a known nephrotoxic agent.

Paediatric.

Granisetron concentrated injection 20 microgram/kg was compared to chlorpromazine (0.5 mg/kg) plus dexamethasone (2 mg/m2) in 88 paediatric patients treated with ifosfamide > 3 g/m2 for two or three days. Granisetron was administered on each day of ifosfamide treatment. At 24 hours, 22% of granisetron patients achieved complete response (no vomiting and no moderate or severe nausea in 24 hours) compared with 10% on the chlorpromazine/ dexamethasone regimen. The median number of vomiting episodes was significantly lower in patients receiving granisetron than in patients receiving the combination of chlorpromazine/ dexamethasone (1.5 vs 7).
The efficacy and safety of intravenous doses of 10, 20 and 40 microgram/kg were compared in 80 children undergoing highly emetogenic chemotherapy. The median number of vomiting episodes were 2, 3, and 1 and the percentage of patients with no more than one vomiting episode were 48, 42 and 56% respectively. There were no dose related safety issues.
Very limited data are available on the use of granisetron in the treatment of children with nausea and vomiting induced by cytostatic chemotherapy.

Radiotherapy.

Granisetron concentrated injection 3 mg was compared to a combination of intravenous (i.v.) metoclopramide (20 mg), dexamethasone (6 mg/m2), and lorazepam (2 mg) in 30 patients to assess the efficacy and safety of granisetron for prophylaxis and control of radiotherapy induced emesis. The study drug was administered 1 hour before starting radiation therapy. The antiemetic efficacy of granisetron was significantly more effective than the standard regimen of metoclopramide/ dexamethasone/ lorazepam in preventing radiotherapy induced emesis.
Very limited data are available on the use of granisetron in the treatment of nausea and vomiting induced by radiotherapy.

Indications

Adults.

Granisetron Sandoz concentrated injection is indicated for use in adults for: the prevention and treatment of nausea and vomiting induced by cytotoxic chemotherapy; the prevention of nausea and vomiting induced by radiotherapy.

Children.

Granisetron Sandoz concentrated injection is indicated for the prevention of nausea and vomiting induced by cytotoxic chemotherapy.

Contraindications

Granisetron Sandoz is contraindicated in patients hypersensitive to granisetron or any of the excipients.

Precautions

As granisetron may reduce lower bowel motility, patients with signs of subacute intestinal obstruction should be monitored following administration of Granisetron Sandoz.
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 comorbidities, on cardiotoxic 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).
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.
No special precautions are required for the elderly or patients with renal or hepatic impairment.

Carcinogenicity/ mutagenicity.

In a 24 month carcinogenicity study, mice were treated with granisetron in the diet at 1, 5 or 50 mg/kg/day. There was a statistically significant increase in the incidence of hepatocellular carcinomas in males and of hepatocellular adenomas in females dosed with 50 mg/kg/day.
The incidence of hepatic tumours was not affected at 1 mg/kg/day.
In a 24 month carcinogenicity study, rats were treated with granisetron in the diet at 1, 5 or 50 mg/kg/day (reduced to 25 mg/kg/day at week 59 because of toxicity). Systemic exposure at the highest dose level was 1.7 times higher than that in humans at the recommended dose.
There was a statistically significant increase in the incidence of hepatocellular carcinomas and adenomas in males dosed with 5 mg/kg/day and above, and in females dosed with 50 mg/kg/day. No increase in liver tumours was observed in rats at a dose of 1mg/kg/day in males and 5 mg/kg/day in females.
Experimental evidence in rats shows that granisetron exhibits the characteristics of a promoter of liver tumours with a clear no effect dose of 1 mg/kg. The probable mechanism for this effect is sustained liver cell hyperplasia. In a study in which rats were treated for 12 months with 100 mg/kg/day, the observed promoting effects were reversible upon cessation of treatment. Additionally, there was no adverse effect on the liver of dogs treated orally for 12 months with granisetron 5 mg/kg/day.
Granisetron did not cause gene mutation in bacterial assays in Salmonella and E.coli or in a mouse lymphoma cell assay. No evidence of chromosomal damage was observed in human lymphocytes in vitro, or in a mouse micronucleus test. There was no evidence of DNA damage in assays of unscheduled DNA synthesis (UDS) in rat hepatocytes in vitro, or ex vivo. There was an apparent increase in UDS in HeLa cells exposed to granisetron in vitro when DNA synthesis was measured by scintillation counting of incorporated radioactive thymidine. However, when this test was repeated using a more definitive autoradiographic method, the test was negative for UDS. It is likely that the apparent UDS in the initial study was, in fact, a reflection of DNA synthesis in cells undergoing normal division (mitogenic activity).

Use in pregnancy.

(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 Sandoz should be used during pregnancy only if clearly needed.

Use in lactation.

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.

Interactions

Granisetron Sandoz 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 antiulcer medications commonly prescribed with antiemetic 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 has 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.

Adverse Effects

Granisetron Sandoz has been well tolerated in human studies. In common with other drugs of this class, headache and constipation have been the most frequently noted adverse events, but the majority have been mild or moderate in nature and tolerated by patients.
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 the tables above 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: 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.

Common: fever.

Cardiovascular.

Common: hypertension.
Rare: hypotension, arrhythmias, sinus bradycardia, atrial fibrillation, varying degrees of A-V block, ventricular ectopy including nonsustained tachycardia, ECG abnormalities, angina pectoris, syncope.

Hypersensitivity.

Rare: hypersensitivity reactions (e.g. anaphylaxis, shortness of breath, hypotension, urticaria).

Hepatic.

Common: transient increases in AST and ALT. These are generally within the normal range and have been reported at similar frequency in patients receiving comparator therapy.

Nervous system.

Common: agitation, anxiety, CNS stimulation, dizziness, insomnia, somnolence.
Rare: extrapyramidal syndrome (only in presence of other drugs associated with this syndrome).

Dermatological.

Common: skin rashes.

Special senses.

Common: taste disorder.
Other common events often associated with chemotherapy also have been reported: leucopenia, decreased appetite, anaemia, alopecia, thrombocytopenia.

Dosage and Administration

Chemotherapy induced nausea and vomiting.

Intravenous administration.

Adults.

For prevention of nausea and vomiting in adults, a single dose of 3 mg of Granisetron Sandoz should be administered as an intravenous infusion, diluted in 20 to 50 mL infusion fluid and administered over 5 minutes prior to the start of chemotherapy. The infusion should be commenced within 30 minutes before the start of chemotherapy.
Prophylactic administration of Granisetron Sandoz should be completed prior to the start of chemotherapy.
In clinical trials, the majority of patients have required only a single dose of granisetron to control nausea and vomiting over 24 hours.
For treatment of established nausea and vomiting in adults, a single dose of 1 mg of Granisetron Sandoz should be administered as a 5 minute infusion. Further treatment doses of Granisetron Sandoz may be administered if required at least 10 minutes apart. The maximum dose of Granisetron Sandoz is 9 mg/24 hours.
In trials, patients have received a total dose of 160 microgram/kg of intravenous granisetron in one day. There is also clinical experience in patients receiving a total of 600 microgram/kg of intravenous granisetron over 5 days.

Children.

The recommended intravenous dose of Granisetron Sandoz in children is 20 microgram to 40 microgram/kg body weight (up to 3 mg), which should be administered as an intravenous infusion, diluted in 10 to 30 mL infusion fluid and administered over 5 minutes, no more than 30 minutes before the start of chemotherapy.

Radiotherapy induced nausea and vomiting.

Intravenous administration.

Adults.

For prevention of nausea and vomiting in adults, a single dose of 3 mg of Granisetron Sandoz should be administered as an intravenous infusion, diluted in 20 to 50 mL infusion fluid and administered over 5 minutes prior to the start of radiotherapy.

Special dosage instructions.

No dosage adjustment is required for the elderly, renally impaired or hepatically impaired (see Pharmacokinetics in special populations).

Combination with a corticosteroid.

The efficacy of IV granisetron can be enhanced by the addition of an intravenous corticosteroid. For example, 8-20 mg of dexamethasone administered prior to the start of cytostatic therapy, or 250 mg methlyprednisolone prior to the start of chemotherapy and again just after the end of chemotherapy.

Preparing the infusion

Adults.

To prepare the dose of 3 mg, withdraw 3 mL from the vial and dilute with a compatible infusion fluid (see below) to a total volume of 20 to 50 mL, in any of the following solutions: 0.9% sodium chloride, 0.18% sodium chloride and 4% glucose, 5% glucose, Hartmann's solution, 1.85% sodium lactate, mannitol i.v. solutions.

Children.

To prepare the dose of 40 microgram/kg, the appropriate volume is withdrawn (up to 3 mL from the vial) and diluted with infusion fluid (as for adults) to a total volume of 10 to 30 mL.
The injectable presentations contain no antimicrobial agent.
Use in one patient on one occasion only. Discard any unused portion.
Granisetron Sandoz concentrated injection has been shown to be stable for 24 hours in the cited solutions when stored at ambient temperature in normal room lighting conditions. To reduce microbiological hazard, use as soon as possible after dilution. If storage is necessary, hold at 2-8°C for not more than 24 hours.
As a general precaution, granisetron should not be mixed in solution with other drugs.
Admixtures of granisetron hydrochloride and dexamethasone sodium phosphate are compatible at concentrations of 10 to 60 microgram/mL granisetron and 80 to 480 microgram/mL dexamethasone phosphate in either 0.9% sodium chloride or 5% glucose intravenous infusion fluids. Stability data have been provided to demonstrate the physical and chemical stability of these solutions when stored at 25°C exposed to strong light for up to 24 hours. To reduce microbiological contamination hazards, it is recommended that admixing should be affected immediately prior to use and infusion commenced as soon as practicable after preparation. The admixture will have a shelf life of 24 hours.
Parenteral drug products should be inspected visually for particulate matter and discolouration before administration whenever solution and container permit.

Overdosage

Contact the Poisons Information Centre on 131 126 for advice on management of overdose.
There is no specific antidote for Granisetron Sandoz. In the case of overdosage, symptomatic treatment should be given.
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.

Presentation

Concentrate for injection (clear, colourless to slightly yellow), 1 mg/mL:1's*, 5's; 3 mg/3 mL: 1's, 5's* (clear glass vial with rubber stopper and flip off aluminium seal).
*Not currently marketed in Australia.

Storage

Stored below 25°C. Protect from light. Do not freeze.

Poison Schedule

S4.