INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo ASPEN ONDANSETRON 4 MG/2 ML
ASPEN ONDANSETRON 8 MG/4 ML

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

ASPEN ONDANSETRON 4 MG/2 ML
(Liquid Injection)
ASPEN ONDANSETRON 8 MG/4 ML
(Liquid Injection)

COMPOSITION
Each mL contains Ondansetron Hydochloride USP equivalent to 2 mg
Ondansetron

PHARMACOLOGICAL CLASSIFICATION
A5.10 Medicines affecting autonomic functions. Serotonin antagonists.

PHARMACOLOGICAL ACTION
Ondansetron is a selective 5-HT
3 receptor-antagonist. Chemotherapeutic agents and radiotherapy may cause release of 5-HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5-HT3 receptors. The initiation of this reflex is blocked by ondansetron. Activation of vagal afferents may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism.
Thus the effect of ondansetron in the management of the nausea and vomiting induced by chemotherapy and radiotherapy may be due to the antagonism of 5-HT
3 receptors on neurons located both in the peripheral and central nervous system.
In psychomotor testing, ondansetron does not cause sedation nor impair performance.
Pharmacokinetics:
Plasma prolactin concentrations are not altered by ondansetron. Ondansetron is rapidly absorbed following oral administration, with maximum plasma concentrations of about 30 ng/mL being attained approximately 1,6 hours after an 8 mg dose.
The disposition of ondansetron following both intravenous and oral dosing is similar with a terminal elimination half life of about 3 hours and a steady-state volume of distribution of about 140 L. Plasma protein binding is 70-76%. Ondansetron is cleared from the systemic circulation predominantly by metabolism with less than 5% of a dose excreted unchanged in the urine.
Studies in healthy elderly volunteers have shown a prolonged elimination half-life (5 hrs) and slightly increased bioavailability (65%) for ondansetron.
As a result of reduced pre-systemic metabolism in patients with severe hepatic impairment, the systemic clearance of ondansetron is markedly reduced with prolonged elimination
half–lives (15–32 hrs) and an oral bioavailability approaching 100%.

INDICATIONS
ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML is indicated for the management of nausea and vomiting induced by chemotherapy and radiotherapy.
ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML is also indicated for the prevention and treatment of post-operative nausea and vomiting.
Routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and vomiting will occur.

CONTRA-INDICATIONS
ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML is contra-indicated in patients known to have hypersensitivity to ondansetron or any of the ingredients of the preparation.
The use of ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML for post-operative nausea and vomiting is contra-indicated in pregnancy.

WARNINGS
Patients with hepatic impairment:
In patients with moderate or severe impairment of hepatic function, clearance of ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML is significantly reduced and serum half-life significantly prolonged. In such patients, a total daily dose of 8 mg should not be exceeded.

PREGNANCY AND LACTATION
Pregnancy: Safety in pregnancy has not been established.
Lactation: Tests have shown that ondansetron passes into the milk of lactating animals.
It is therefore recommended that mothers receiving ASPEN ONDANSETRON 4 MG/ML and ASPEN ONDANSETRON 8 MG/4 ML should not breast feed their babies.

DOSAGE AND DIRECTIONS FOR USE:
Chemotherapy and radiotherapy induced nausea and vomiting:
The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used.
Adults:
Emetogenic chemotherapy and radiotherapy.
For most patients receiving emetogenic chemotherapy or radiotherapy ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML, 8 mg should be administered as a slow IV or IM injection immediately before treatment.
Highly Emetogenic Chemotherapy:
A single dose of ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML, 8 mg by slow IV or IM 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 severity of the emetogenic challenge.
In these patients the following dose schedules have been shown to be effective:
A dose of 8 mg by slow IV or IM injection immediately before chemotherapy, followed by two further IV or IM doses of 8 mg two to four hours apart, or by constant infusion of 1 mg/hour for up to 24 hours.
OR
A single dose of 32 mg diluted in 50–100 mL of saline or other compatible infusion fluid, infused over not less than 15 minutes immediately before chemotherapy.
The efficacy of ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of dexamethasone phosphate 20 mg administered 30–45 minutes prior to the first ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML dose prior to chemotherapy.
Children:
Experience is currently limited, but ondansetron was effective and well tolerated in children over the age of 4 years, when given intravenously at a dose of 5 mg/m2 over 15 minutes, immediately before chemotherapy.
For prevention of post-operative nausea and vomiting in paediatric patients two years and older having surgery performed under general anaesthesia, ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML , 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 the treatment of established post-operative nausea and vomiting in paediatric patients two years and older ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML may be administered by slow intravenous injection at a dose of 0,1 mg/kg up to a maximum of 4 mg.
Repeat dosing for paediatric patients who continue to experience nausea and/or vomiting has not been studied, and should thus not be given.
Elderly patients:
Efficacy and tolerance in patients over 65 years was similar to that seen in younger adults indicating no need to alter dosage or route of administration in the elderly.

Prevention and Treatment of post-operative nausea and vomiting:
Adults:
Immediately before induction of anaesthesia, or post-operatively if the patient experiences nausea and/or vomiting occurring shortly after surgery, administer 4 mg undiluted intramuscularly or intravenously. If given intravenously, it must be administered in not less than 30 seconds, preferably over 2 –5 minutes.
Repeat dosing for patients who continue to experience nausea and/or vomiting postoperatively has not been studied. While recommended as a fixed dose for all, few patients above 80 kg or below 40 kg have been studied.
Children:
For prevention of post-operative nausea and vomiting in paediatric patients two years and older having surgery performed under general anaesthesia, ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML 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 the treatment of established post–operative nausea and vomiting in paediatric patients two years and older, ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML may be administered by slow intravenous injection at a dose of 0,1 mg/kg up to a maximum of 4 mg.
Repeat dosing for paediatric patients who continue to experience nausea and/or vomiting has not been studied, and should thus not be given.
Elderly:
Safety and efficacy have not been established with the use of ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML in the prevention and treatment of post-operative nausea and vomiting in the elderly.

Patients with renal/hepatic impairment:
Patients with renal impairment: No alteration of daily dosage or frequency of dosing, or route of administration is required. There is limited information available on severe renal or hepatic impairment.
Patients with hepatic impairment: Clearance of ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML is significantly reduced and serum half-life significantly prolonged in patients with moderate or severe impairment of hepatic function.
In such patients, a total daily dose of 8 mg should not be exceeded.
ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML injection should not be administered in the same syringe or infusion as any other medication.
ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML injection ampoules should not be autoclaved.

Compatibility with intravenous fluids:
Compatability studies have been undertaken, ondansetron is stable in the following infusion solutions:
Sodium chloride 0,9% m/v intravenous infusion
Glucose 5% m/v intravenous infusion
Ringers intravenous infusion
Potassium chloride 0,3% m/v and sodium chloride 0,9% m/v intravenous infusion
Potassium chloride 0,3% m/v and glucose 5% m/v intravenous infusion.
Intravenous solutions should be prepared at the time of infusion. Ondansetron has been shown to be stable for seven days at room temperature in these infusion solutions.

Compatibility with other medicines
Cisplatin: concentrations of up to 0,48 mg/mL (e.g. 240 mg in 500 mL) administered over one to eight hours.
Dexamethasone: Dexamethasone sodium phosphate 20 mg may be administered as a slow intravenous injection over 2–5 minutes via the Y-site of an infusion set delivering 8 mg of ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML diluted in 50-100 mL of a compatible infusion fluid over approximately 15 minutes.
Compatibility between dexamethasone sodium phosphate and ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML has been demonstrated supporting administration of these drugs through the same giving set, with resulting in-line concentrations in the ranges of 32 µg- 2,5 mg/mL for dexamethasone sodium phosphate and 8 µg–1 mg/mL for ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML.
5–Fluorouracil: Concentrations up to 0,8 mg/mL (e.g. 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 5–Fluorouracil may contain up to 0,045% m/v magnesium chloride in addition to other excipients shown to be compatible.
Carboplatin: Concentrations in the range of 0,18 mg/mL to 9,9 mg/mL (e.g. 90 mg in 500 mL to 990 mg in 100 mL), administered over 10 minutes to one hour.
Etoposide: Concentrations in the range of 0,14 mg/mL to 0,25 mg/mL (e.g. 72 mg in 500 mL to 250 mg in 1 litre), administered over 30 minutes to one hour.
Ceftazidime: Doses in the range of 250 mg to 2000 mg reconstituted with Water for Injection BP, as recommended by the manufacturer (e.g. 2,5 mL for 250 mg and 10 mL for 2 g ceftazidime), and given as an intravenous bolus injection over approximately five minutes.
Cyclophosphamide: Doses in the range of 100 mg to 1 g reconstituted with Water for Injection BP, 5 mL per 100 mg cyclophosphamide, as recommended by the manufacturer, and given as an intravenous bolus injection over approximately five minutes.
Doxorubicin: Doses in the range of 10 to 100 mg, reconstituted with Water for Injection BP, 5 mL per 10 mg doxorubicin, as recommended by the manufacturer, and given as an intravenous bolus injection over approximately five minutes.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
The following side effects can occur:
Incidence : Frequently
Central nervous system
: Headache
Gastrointestinal system: Increase in large bowel transit time is known to be caused by ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML which may cause constipation in some patients.
Incidence: Less frequently
Cardiovascular system
: Arrhythmias, hypotension, bradycardia and chest pain.
Central Nervous System: Seizures have been observed rarely.
Hypersensitivity reactions: Immediate hypersensitivity reactions, sometimes severe (e.g. anaphylaxis, bronchospasm, shortness of breath, hypotension, shock, angiodema, urticaria) have been reported.
Local reactions: Pain, redness and burning at site of injection.
Musculoskeletal: There have been rare reports of involuntary movement disorders without definitive evidence of persistent clinical sequelae.
Other:
A sensation of warmth or flushing, hiccups and transient, asymptomatic increases in aminotransferases Dizziness and transient visual disturbances (e.g. blurred vision) have been reported during or shortly after rapid intravenous administration of ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML.

Special precautions:
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.
Patients with subacute intestinal obstructions should be monitored following administration, as ASPEN ONDANSETRON 4 MG/2 ML and ASPEN ONDANSETRON 8 MG/4 ML is known to increase large bowel transit time.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See SIDE-EFFECTS AND SPECIAL PRECAUTIONS. Manifestations that have been reported include severe constipation, visual disturbances, hypotension, and vasovagal episode with transient second degree AV block, In cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate, as there is no specific antidote for ondansetron.

IDENTIFICATION:
A colourless liquid free from particulate matter.

PRESENTATION:
ASPEN ONDANSETRON 4 MG/2 ML Clear, colourless 2 mL glass ampoules with ceramic print, placed in a plastic rondo tray covered with a rondo tray sponge, packed into a carton. Each carton contains 5 ampoules.
ASPEN ONDANSETRON 8 MG/4 ML Clear, colourless 5 mL glass ampoules with ceramic print, placed in a plastic rondo tray covered with a rondo tray sponge, packed into a carton. Each carton contains 5 ampoules.

STORAGE INSTRUCTIONS:
Store below 25°C. Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
ASPEN ONDANSETRON 4 MG/2 ML: A39/5.10/0062
ASPEN ONDANSETRON 8 MG/4 ML: A39/5.10/0063

NAME AND BUSINESS ADDRESS OF THE HOLDER OF CERTIFICATE OF REGISTRATION:
PHARMACARE LIMITED
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
4 March 2005

050505

New addition to this site: January 2006
Source: Pharmaceutical Industry

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