ONDANSETRON

Posology Chemotherapy and radiotherapy induced nausea and vomiting (CINV and RINV) 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, intravenous or intramuscular administration. The recommended oral dose is 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, oral or rectal treatment with Ondansetron may be continued for up to 5 days after a course of treatment.

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

Paediatric Population:

CINV in children and adolescents (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. 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.

Tabulated list of adverse reactions 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 (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) 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. Immune system disorders Rare Immediate hypersensitivity reactions sometimes severe, including anaphylaxis. Nervous system disorders Very common Headache.

Uncommon Seizures, movement disorders (including extrapyramidal reactions such as dystonic reactions, oculogyric crisis and dyskinesia)(1). Rare Dizziness predominantly during rapid IV administration. g. blurred vision) predominantly during IV administration.

Very rare Transient blindness predominantly during IV administration (2). Cardiac disorders Uncommon Arrhythmias, chest pain with or without ST segment depression, bradycardia. Rare QTc prolongation (including Torsade de Pointes). 4) Vascular disorders Common Sensation of warmth or flushing.

Uncommon Hypotension. Respiratory, thoracic and mediastinal disorders Uncommon Hiccups. Gastrointestinal disorders Common Constipation. Hepatobiliary disorders Uncommon Asymptomatic increases in liver function tests (3). 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.

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.

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.

Hypokalaemia and hypomagnesaemia should be corrected prior to ondansetron administration. 5). 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.

Paediatric Population:

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

1. 5)