ONDANSETRON

Chemotherapy and radiotherapy induced nausea and vomiting.

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 (as an orodispersible tablet) intravenous or intramuscular administration. For oral administration: 8 mg taken 1 to 2 hours before chemotherapy or radiation treatment, followed by 8 mg 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 24 mg Ondansetron taken with 12 mg 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, treatment with Ondansetron may be continued for up to 5 days after a course of treatment.

The recommended dose is 8 mg to be taken twice daily.

Paediatric population:

CINV in children aged ≥ 6 months to 17 years. 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.

4). 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 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 to 17 years. 2m2 5mg/m2 or 8mg IV plus 8mg syrup or tablet after 12 hours 8mg syrup or tablet every 12 hours 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 32mg.

1). 15mg/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 32mg.

Table 2:

Weight-based dosing for Chemotherapy - Children aged ≥6 months to 17 years. 15mg/kg IV every 4 hours 4 mg syrup or tablet every 12 hours 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 32mg.

Elderly:

No alteration of oral dose or frequency of administration is required.

Post-operative nausea and vomiting (PONV) Adults:

For the prevention of PONV: Ondansetron may be administered either orally (as an orodispersible tablet) or by intravenous or intramuscular injection. For oral administration: 16mg taken 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 to 17 years: 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.

1mg/kg up to a maximum of 4mg either prior to, at or after induction of anaesthesia. 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/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 […]

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) and very rare (<1/10,000). Very common, common and uncommon events were generally determined from clinical trial data.

The incidence in placebo was taken into account. Rare and very rare events were generally determined from post-marketing spontaneous data. The following frequencies are estimated at the standard recommended doses of ondansetron. The adverse event profiles in children and adolescents were comparable to that seen in adults.

System Organ Class Very Common Common Uncommon Rare Very Rare Not known 1 Observed without definitive evidence of persistent clinical sequelae. 2 The majority of the blindness cases reported resolved within 20 minutes. Most patients had received chemotherapeutic agents, which included cisplatin.

Some cases of transient blindness were reported as cortical in origin. 3 These events were observed commonly in patients receiving chemotherapy with cisplatin. Reporting of suspected adverse reactions Immune system disorders Immediate hypersensitivity reactions sometimes severe, including anaphylaxis.

Nervous system disorders Headache. g. blurred vision) predominantly during IV administration Transient blindness predominantly during IV administration (2) Cardiac disorders Arrhythmias, chest pain with or without ST segment depression, bradycardia.

4) Vascular disorders Sensation of warmth or flushing. Hypotension. Respiratory, thoracic and mediastinal disorders Hiccups. Gastrointestinal disorders Constipation. Hepatobiliary disorders Asymptomatic increases in liver function tests (3) Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HT3 receptor antagonists. Respiratory events should be treated symptomatically and clinicians should pay particular attention to them as precursors of hypersensitivity reactions.

1). In addition, post-marketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc, including patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation or electrolyte abnormalities.

Hypokalaemia and hypomagnesaemia should be corrected prior to Ondansetron administration. There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of ondansetron and other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRIs)).

If concomitant treatment with ondansetron and other serotonergic drugs is clinically warranted, appropriate observation of the patient is advised. As ondansetron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.

In patients with adenotonsillar surgery prevention of nausea and vomiting with ondansetron may mask occult bleeding. Therefore, such patients should be followed carefully after ondansetron. Cases of myocardial ischemia have been reported in patients treated with ondansetron.

In some patients, especially in the case of intravenous administration, symptoms appeared immediately after administration of ondansetron. Patients should be alerted to the signs and symptoms of myocardial ischaemia.

Paediatric population:

Paediatric patients receiving Ondansetron with hepatotoxic chemotherapeutic agents should be monitored closely for impaired hepatic function.

CINV:

When calculating the dose on an mg/kg basis and administering three doses at 4-hour intervals, the total daily dose will be higher than if one single dose of 5mg/m2 followed by an oral dose is given. The comparative efficacy of these two different dosing regimens has not been investigated in clinical trials.

1). Excipient(s) with known effect Ondansetron orodispersible tablets contain aspartame and therefore should be taken with caution in patients with phenylketonuria. Neither non-clinical nor clinical data are available to assess aspartame use in infants below 12 weeks of age.

Ondansetron orodispersible tablets contain small amounts of sulphur dioxide that may rarely cause severe hypersensitivity reactions and bronchospasm. 88mg of sorbitol in each tablet. This medicine contains less than 1 mmol sodium (23mg) per 4mg tablet, that is to say essentially ‘sodium-free’.

Patients with rare glucose-galactose malabsorption should not take this medicine.

1. 5).