ONDANSETRON-AFT SOLUTION FOR INJECTION 2MG/ML [SIN15006P]

Product Info

ONDANSETRON-AFT SOLUTION FOR INJECTION 2MG/ML

[SIN15006P]

4. INDICATIONS

Adults:
Ondansetron-AFT is indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. Ondansetron-AFT is indicated for the prevention and treatment of post-operative nausea and vomiting (PONV).

Paediatric Population:
Ondansetron-AFT is indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in children, and for the prevention and treatment of PONV in children.

5. DOSAGE AND ADMINISTRATION

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

The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The selection of dose regimen should be determined by the severity of the emetogenic challenge.

CINV and RINV in Adults

The recommended intravenous (IV) or intramuscular (IM) dose of ONDANSETRON-AFT is 8 mg administered immediately before treatment.

For highly emetogenic chemotherapy, a maximum initial ondansetron dose of 16 mg IV infused over 15 minutes may be used. A single IV dose greater than 16 mg should not be given due to dose-dependent increase of QT prolongation risk (see Warnings and Precautions, Adverse Reactions, Pharmacodynamic Effects – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

The efficacy of ONDANSETRON-AFT in highly emetogenic chemotherapy may be enhanced by the addition of a single IV dose of dexamethasone sodium phosphate 20 mg, administered prior to chemotherapy.

IV doses greater than 8 mg and up to a maximum of 16 mg must be diluted in 50 mL to 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection before administration and infused over not less than 15 minutes (see Instructions for Use and Handling). ONDANSETRON-AFT doses of 8 mg or less, do not need to be diluted and may be administered as a slow IM or IV injection in not less than 30 seconds.

The initial dose of ONDANSETRON-AFT may be followed by 2 additional IV or IM doses of 8 mg 2 to 4 hours apart, or by a constant infusion of 1 mg/h for up to 24 hours.

Oral treatment is recommended to protect against delayed or prolonged emesis after the first 24 hours.

CINV in Children and Adolescents (aged 2 years and over)

In children with a body surface area of 0.6 to 1.2 m² ondansetron is administered as a single IV dose of 5 mg/m² immediately before chemotherapy, followed by 4 mg orally 12 hours later. 4 mg orally twice daily can be continued for up to five days after a course of treatment.

CINV and RINV in Elderly

In patients 65 to 74 years of age, the initial IV dose of ONDANSETRON-AFT 8 mg or 16 mg, infused over 15 minutes may be followed by 2 doses of 8 mg infused over 15 minutes and given no less than 4 hours apart. All IV doses should be diluted in 50–100 mL of saline or other compatible infusion fluid and infused over 15 minutes.

In patients 75 years of age or older, the initial IV dose of ONDANSETRON-AFT should not exceed 8 mg infused over 15 minutes. The initial dose of 8 mg may be followed by 2 doses of 8 mg, infused over 15 minutes and given no less than 4 hours apart (see Special Patient Populations, Elderly – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). All IV doses should be diluted in 50–100 mL of saline or other compatible infusion fluid and infused over 15 minutes.

Renal Impairment

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

Hepatic Impairment

Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg IV or oral should not be exceeded.

Patients with Poor Sparteine/Debrisoquine Metabolism

The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Consequently, in such patients repeat dosing will give drug exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing is required.

POST-OPERATIVE NAUSEA AND VOMITING

PONV in Adults

For prevention of post-operative nausea and vomiting, the recommended dose of ONDANSETRON-AFT injection is a single dose of 4 mg by IM or slow IV injection administered at the induction of anaesthesia.

For treatment of established post-operative nausea and vomiting a single dose of 4 mg given by IM or slow IV injection is recommended.

PONV in Children and Adolescents (aged 2 years and over)

For prevention and treatment of PONV in paediatric patients having surgery performed under general anaesthesia, ONDANSETRON-AFT may be administered by slow IV injection (not less than 30 seconds) at a dose of 0.1 mg/kg up to a maximum of 4 mg either prior to, at or after induction of anaesthesia, or after surgery.

There is limited data on the use of ONDANSETRON-AFT in the prevention and treatment of PONV in children under 2 years of age.

Elderly

There is limited experience in the use of ONDANSETRON-AFT in the prevention and treatment of post- operative nausea and vomiting in the elderly, however ONDANSETRON-AFT is well tolerated in patients over 65 years receiving chemotherapy.

Renal Impairment

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

Hepatic Impairment

Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg IV or oral should not be exceeded.

Patients with Poor Sparteine/Debrisoquine Metabolism

The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Consequently in such patients repeat dosing will give drug exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing is required.

Instruction for Use/Handling

Ondansetron-AFT Injection should not be autoclaved.

Compatibility with Intravenous Fluids

Ondansetron-AFT injection should only be mixed with those infusion solutions which are recommended:

• 0.9%w/v Sodium Chloride Intravenous Infusion BP

• 5%w/v Glucose Intravenous Infusion BP

• 10%w/v Mannitol Intravenous Infusion BP

• Ringers Intravenous Infusion

• 0.3%w/v Potassium Chloride and 0.9%w/v Sodium Chloride Intravenous Infusion BP

• 0.3%w/v Potassium Chloride and 5%w/v Glucose Intravenous Infusion BP

Compatibility studies have been undertaken in polyvinyl chloride infusion bags and polyvinyl chloride administration sets. It is considered that adequate stability would also be conferred by the use of polyethylene infusion bags or Type 1 glass bottles. Dilutions of ondansetron injection in sodium chloride 0.9%w/v or in glucose 5%w/v have been demonstrated to be stable in polypropylene syringes. It is considered that ondansetron injection diluted with other compatible infusion fluids would be stable in polypropylene syringes.

Compatibility with other drugs: Ondansetron-AFT may be administered by intravenous infusion at 1mg/hour, e.g. from an infusion bag or syringe pump. The following drugs may be administered via the Y-site of the ondansetron injection giving set for ondansetron concentrations of 16 to 160 micrograms/mL (e.g. 8 mg/500 mL and 8 mg/50 mL respectively).

Cisplatin: Concentrations up to 0.48 mg/mL (e.g. 240 mg in 500 mL) administered over one to eight hours.

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 cause precipitation of ondansetron. The 5- fluorouracil infusion may contain up to 0.045%w/v magnesium chloride in addition to other excipients shown to be compatible.

Carboplatin: Concentrations in the range 0.18 mg/mL to 9.9 mg/mL (e.g., 90 mg in 500 mL to 990 mg in 100 mL), administered over ten minutes to one hour.

Etoposide: Concentrations in the range 0.14 mg/mL to 0.25 mg/mL (e.g., 72 mg in 500 mL to 250 mg in 1 litre), administered over thirty minutes to one hour.

Ceftazidime: Doses in the range 250 mg to 2000 mg reconstituted with Water for Injections 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 100 mg to 1 g, reconstituted with Water for Injections 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 10–100 mg reconstituted with Water for Injections BP, 5 mL per 10 mg doxorubicin, 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 via the Y-site of an infusion set delivering 8 or 16 mg of ondansetron diluted in 50–100 mL of a compatible infusion fluid over approximately 15 minutes. Compatibility between dexamethasone sodium phosphate and ondansetron has been demonstrated supporting administration of these drugs through the same giving set resulting in concentrations in line of 32 microgram – 2.5 mg/ mL for dexamethasone sodium phosphate and 8 microgram -1 mg/mL for ondansetron.

The solution for injection formulation contains no antimicrobial preservative. Use in one patient on one occasion only and injected or diluted immediately after opening. Any remaining solution should be discarded.

6. CONTRAINDICATIONS

Concomitant use with apomorphine (see section DRUG INTERACTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Hypersensitivity to any component of the preparation.