ONDANSETRON Syrup Ref.[7026] Active ingredients: Ondansetron

Posology

Chemotherapy and radiotherapy induced nausea and vomiting (CINV)

Adults

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.

Emetogenic chemotherapy and radiotherapy: Ondansetron can be given either by rectal, oral (tablets or syrup), intravenous or intramuscular administration.

For oral administration: 8mg taken 1 to 2 hours before chemotherapy or radiation treatment, followed by 8mg every 12 hours for a maximum of 5 days to protect against delayed or prolonged emesis.

For highly emetogenic chemotherapy): a single dose of up to 24mg ondansetron taken with 12mg oral dexamethasone sodium phosphate, 1 to 2 hours before chemotherapy, may be used.

To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with Ondansetron should be continued for up to 5 days after a course of treatment. The recommended dose for oral administration is 8mg twice daily.

Paediatric Population

CINV in children aged ≥6 months and adolescents:

The dose for CINV can be calculated based on body surface area (BSA) or weight – see below.

In paediatric clinical studies, ondansetron was given by IV infusion diluted in 25 to 50 mL of saline or other compatible infusion fluid and infused over not less than 15 minutes.

Weight-based dosing results in higher total daily doses compared to BSA-based dosing (sections 4.4).

Ondansetron injection should be diluted in 5% dextrose or 0.9% sodium chloride or other compatible infusion fluid (see section 6.6) and infused intravenously over not less than 15 minutes.

There are no data from controlled clinical trials on the use of ondansetron in the prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use of ondansetron for radiotherapy-induced nausea and vomiting in children.

Dosing by BSA:

Ondansetron should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m². The intravenous dose must not exceed 8 mg.

Oral dosing can commence twelve hours later and may be continued for up to 5 days (Table 1).

The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.

Table 1. BSA-based dosing for Chemotherapy – Children aged ≥6 months and adolescents:

^a The intravenous dose must not exceed 8mg.
^b The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg

Dosing by bodyweight:

Weight-based dosing results in higher total daily doses compared to BSA-based dosing (sections 4.4. and 5.1).

Ondansetron should be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg/kg. The intravenous dose must not exceed 8 mg.

Two further intravenous doses may be given in 4-hourly intervals.

Oral dosing can commence twelve hours later and may be continued for up to 5 days (Table 2). The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32mg.

Table 2. Weight-based dosing for Chemotherapy – Children aged ≥6 months and adolescents:

^a The intravenous dose must not exceed 8mg.
^b The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.

Elderly

Ondansetron is well tolerated by patients over 65 years. No alteration of oral dose or frequency of administration is required.

Post operative nausea and vomiting (PONV)

Adults

For the prevention of PONV: Ondansetron can be administered orally or by intravenous or intramuscular injection.

For oral administration: 16mg one hour prior to anaesthesia.

For the treatment of established PONV: Intravenous or intramuscular administration is recommended.

Paediatric population

PONV in children aged ≥1 month and adolescents:

Oral formulation:

No studies have been conducted on the use of orally administered ondansetron in the prevention or treatment of post-operative nausea and vomiting; slow IV. injection (not less than 30 seconds) is recommended for this purpose.

Injection:

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

For the treatment of PONV after surgery in paediatric patients having surgery performed under general anaesthesia, a single dose of Ondansetron may be administered by slow intravenous injection (not less than 30 seconds) at a dose of 0.1mg/kg up to a maximum of 4mg.

There are no data on the use of ondansetron in the treatment of PONV in children below 2 years of age.

Elderly

There is limited experience in the use of Ondansetron in the prevention and treatment of PONV in the elderly, however Ondansetron is well tolerated in patients over 65 years receiving chemotherapy.

For both indications

Patients with Renal impairment

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

Patients with 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 8mg should not be exceeded.

Patients with poor Sparteine/Debrisoguine 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 are required.

Method of administration

Oral.

Symptoms

There is limited experience of ondansetron overdose. In the majority of cases, symptoms were similar to those already reported in patients receiving recommended doses (see section 4.8). Manifestations that have been reported include visual disturbances, severe constipation, hypotension and a vasovagal episode with transient second degree AV block.

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

Paediatric population

Paediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeded estimated ingestion of 4 mg/kg) in infants and children aged 12 months to 2 years.

Management

There is no specific antidote for ondansetron, therefore in all cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

The use of ipecacuanha to treat overdose with ondansetron is not recommended, as patients are unlikely to respond due to the anti-emetic action of ondansetron itself.

Shelf life: 2 years unopened.

Once opened, use within 28 days.

No special requirements.

A type III amber glass bottle with a tamper evident aluminium cap with an EPE liner, or a child resistant polypropylene cap with an EPE liner, containing 50ml.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.