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 route of administration and dose ondansetron should be flexible in the range of 8-32 mg a day and selected as shown below.

Emetogenic chemotherapy and radiotherapy:

Ondansetron can be given either by rectal, oral (tablets or syrup), intravenous or intramuscular administration. The recommended oral dose is: 8 mg 1-2 hours before treatment, followed by 8 mg 12 hours later. 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 oral dose is 8 mg to be taken twice daily. g. g. high-dose cisplatin, ondansetron can be given either by rectal, intravenous or intramuscular administration. The recommended oral dose is 24 mg taken together with oral dexamethasone sodium phosphate 12 mg, 1 to 2 hours before treatment.

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 oral dose is 8 mg to be taken twice daily.

Paediatric Population – Chemotherapy-induced nausea and vomiting (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 (see Instructions for Use and Handling) and infused over not less than 15 minutes.

4). 9% sodium chloride or other compatible infusion fluid (see Use and Handling) 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 (see Table 1 below).

The total daily dose must not exceed adult dose of 32 mg. 6 m2 5 mg/m2 IV 4 mg syrup or tablet after 12 hours 4 mg syrup or tablet every 12 hours a The intravenous dose must not exceed 8 mg. b The total daily dose must not exceed adult dose of 32 mg.

15 mg/kg. The intravenous dose must not exceed 8 mg. Two further intravenous dose may be given in 4-hourly intervals. The total daily dose must not exceed adult dose of 32 mg. Oral dosing can commence twelve hours later and may be continues for up to 5 days (see Table 2 below).

15 mg/kg at 4 hourly intervals 4 mg syrup or tablet every 12 hours. a The intravenous dose must not exceed 8 mg b The total daily dose must not exceed adult dose of 32 mg.

Elderly:

Ondansetron is well tolerated by patients over 65 years and no alteration of dosage, dosing frequency or route of administration are required.

Patients with 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 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 are 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 prevention of post-operative nausea and vomiting, the recommended oral dose is 16 mg given 1 hour prior to anaesthesia.

Alternatively, 8 mg one hour prior to anaesthesia followed by two further doses of 8 mg at eight hourly intervals. For the treatment of established PONV ondansetron administration by injection is recommended. Paediatric population – Post-operative nausea and vomiting in children aged ≥ 1 month and adolescents: No studies have been conducted on the use of orally administered ondansetron in the prevention or treatment of post-operative nausea and vomiting (PONV); slow IV injection (in not less than 30 seconds) is recommended for this purpose.

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

Elderly:

There is limited experience in the use of ondansetron in the prevention and treatment of […]

Tabulated list of adverse reactions Adverse events are listed below by system organ class and frequency. Frequencies are defined according to the following convention: 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), very rare (< 1/10,000; including isolated reports), not known (cannot be estimated from the available data).

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 during rapid IV administration.

g. 4) Vascular disorders Common: feeling of warmth, flushing Uncommon: hypotension Respiratory, thoracic and mediastinal disorders Uncommon: hiccups Gastrointestinal disorders Common: constipation Hepatobiliary disorders Uncommon: asymptomatic increases in liver function tests3 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 commonly observed in patients receiving chemotherapy with cisplatin.

* These types of adverse drug reactions have been derived from post-marketing experience with ondansetron via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as not known Reporting of suspected adverse reactions 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.

Hypokalemia and hypomagnesemia 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. 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. 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.

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 5 mg/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). Excipients Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1. 5).