Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2017 Publisher: Novartis Pharmaceuticals UK Ltd, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR
Zofran Suppositories are indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.
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: Zofran can be given either by rectal, oral (tablets or syrup), intravenous or intramuscular administration.
For rectal administration: The recommended dose of Zofran (ondansetron) Suppositories is one 16 mg suppository given 1 to 2 hours before treatment.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with Zofran should be continued for up to 5 days after a course of treatment. The recommended daily dose for rectal administration is one 16 mg suppository.
Highly emetogenic chemotherapy (e.g. high dose cisplatin): Zofran can be given either by oral, rectal, intravenous or intramuscular administration.
For rectal administration: The recommended dose of Zofran (ondansetron) Suppositories is one 16 mg suppository given 1 to 2 hours before treatment.
The efficacy of Zofran in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of dexamethasone sodium phosphate 20 mg, administered prior to chemotherapy.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with Zofran should be continued for up to 5 days after a course of treatment. The recommended daily dose for rectal administration is one 16 mg suppository.
The use of Zofran Suppositories in children is not recommended. The usual method of administration is IV followed by oral therapy (see below).
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 (see section 4.4).
There are no data from controlled clinical trials on the use of Zofran in the prevention of delayed or prolonged CINV. There are no data from controlled clinical trials on the use of Zofran for radiotherapy-induced nausea and vomiting in children.
Dosing by BSA:
Zofran should be administered immediately before chemotherapy as a single intravenous dose of 5 mg/m². The single intravenous dose must not exceed 8 mg.
Oral dosing can commence 12 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:
| BSA | Day 1a,b | Days 2-6b |
|---|---|---|
| <0.6 m² | 5 mg/m² IV plus | 2 mg syrup every 12 hours |
| 2 mg syrup after 12 hours | ||
| ≥0.6 m² to ≤ 1.2 m² | 5 mg/m² IV plus | 4 mg syrup or tablet every 12 hours |
| 4 mg syrup or tablet after 12 hours | ||
| >1.2 m² | 5 mg/m² or 8 mg IV plus 8 mg syrup or tablet after 12 hours | 8 mg syrup or tablet every 12 hours |
a The intravenous dose must not exceed 8 mg.
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 (see sections 4.4. and 5.1).
Zofran should be administered immediately before chemotherapy as a single intravenous dose of 0.15 mg/kg. The single intravenous dose must not exceed 8 mg.
Two further intravenous doses may be given in 4-hourly intervals.
Oral dosing can commence 12 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 32 mg.
Table 2. Weight-based dosing for Chemotherapy – Children aged ≥6 months and adolescents:
| Weight | Day 1a,b | Days 2-6b |
|---|---|---|
| ≤10 kg | Up to 3 doses of 0.15 mg/kg IV every 4 hours | 2 mg syrup every 12 hours |
| >10 kg | Up to 3 doses of 0.15 mg/kg IV every 4 hours | 4 mg syrup or tablet every 12 hours |
a The intravenous dose must not exceed 8 mg.
b The total dose over 24 hours (given as divided doses) must not exceed adult dose of 32 mg.
No alteration of oral dose or frequency of administration is required.
No alteration of daily dosage or frequency of dosing, or route of administration are required.
Clearance of Zofran 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 should not be exceeded.
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.
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 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.
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.
3 years.
Store below 30°C.
Each suppository is in an individually sealed cavity enclosed in a perforated cardboard mount and packed into a carton.
Insert into the rectum.
For detailed instructions see the patient information leaflet included in every pack.
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