Ondansetron


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Prophylaxis of chemotherapy-induced nausea and vomiting Moderately emetogenic chemotherapy: Initial: 8 mg 0.5-2 hours prior to chemotherapy, then 8 mg dose after 8 or 12 hours. Highly emetogenic chemotherapy: 24 mg as a single dose 0.5-2 hours prior to chemotherapy. Post-operative nausea and vomiting 16 mg as a single dose 1 hour prior to anaesthesia. Alternatively, 8 mg 1 hour prior to anaesthesia followed by 2 further 8 mg doses at 8 hourly intervals. Prevent delayed emesis following cancer chemotherapy 8 mg bid for up to 5 days after a course of treatment. Prevention of nausea and vomiting associated with radiation therapy Total body irradiation: 8 mg 1-2 hours prior to daily fraction of radiotherapy. Single high-dose fraction to the abdomen: 8 mg 1-2 hours prior to irradiation. Fractionated radiation to the abdomen: 8 mg 1-2 hours prior to irradiation, followed by 8 hourly doses repeated daily during the radiotherapy course. IV/IM Prophylaxis of chemotherapy-induced nausea and vomiting Moderately emetogenic chemotherapy: 8 mg or 0.15 mg/kg as a single dose. Highly emetogenic chemotherapy: 8 mg as a single dose immediately prior to treatment, may be followed by either a 1 mg/hour continuous IV infusion for up to 24 hours, or by 2 further doses of 8 mg at 4-hour intervals. Alternatively, 16 mg via IV infusion immediately prior to treatment or 0.15 mg/kg via IV infusion 30 minutes prior to chemotherapy, may be followed by 2 further doses at of 8 mg at 4-hour intervals. Max: 16 mg/dose. Post-operative nausea and vomiting 4 mg via slow IV or IM inj given as single dose at induction of anaesthesia. Prophylaxis of nausea and vomiting associated with radiation therapy 8 mg via slow IV or IM inj as a single dose immediately before treatment. Rectal Nausea and vomiting associated with cancer chemotherapy or radiotherapy As supp: 16 mg given 1-2 hours prior to treatment. Prevent delayed emesis following cancer chemotherapy As supp: 16 mg once daily for up to 5 days after a course of treatment.
Dosage Details
Oral
Prevent delayed emesis following chemotherapy
Adult: 8 mg bid for up to 5 days after a course of treatment.

Oral
Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: Moderately emetogenic chemotherapy: 8 mg given 0.5-2 hours prior to chemotherapy, followed by 8 mg after 8 or 12 hours. Highly emetogenic chemotherapy: 24 mg as a single dose, given 0.5-2 hours prior to chemotherapy.
Child: Moderately emetogenic chemotherapy: 4-11 years 4 mg 30 minutes prior to chemotherapy. Repeat dose at 4 and 8 hours after the initial dose; ≥12-17 years Same as adult dose.

Oral
Postoperative nausea and vomiting
Adult: 16 mg given as a single dose 1 hour prior to induction of anaesthesia. Alternatively, 8 mg 1 hour prior to anaesthesia followed by 2 further doses of 8 mg at 8 hourly intervals.
Child: As oral soluble film: ≥40 kg: 4 mg 1 hour prior to anaesthesia, followed by another 4 mg dose after 12 hours.

Oral
Prophylaxis of nausea and vomiting associated with radiation therapy
Adult: Total body irradiation (TBI): 8 mg 1-2 hours prior to daily fraction of radiotherapy. Single high-dose fraction to the abdomen:  8 mg given 1-2 hours prior to irradiation. Daily fractionated radiation to the abdomen: 8 mg 1-2 hours prior to irradiation, followed by 8 hourly doses repeated daily during the radiotherapy course.

Parenteral
Postoperative nausea and vomiting
Adult: 4 mg via slow IV or IM inj given as single dose at induction of anaesthesia.
Child: ≥1 month ≤40 kg: 0.1 mg/kg via slow IV inj at anaesthesia induction; >40 kg: 4 mg via slow IV inj as a single dose at induction of anaesthesia. Max: 4 mg/dose.

Parenteral
Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: Moderately emetogenic chemotherapy: 8 mg via slow IV inj as a single dose. Alternatively, 0.15 mg/kg via slow IV inj as a single dose. Highly emetogenic chemotherapy: 8 mg via slow IV or IM inj as a single dose immediately prior to treatment, may be followed by either a 1 mg/hour continuous IV infusion for up to 24 hours, or by 2 further doses of 8 mg at 4-hour intervals. Alternatively, 16 mg via IV infusion over at least 15 minutes immediately prior to treatment; or 0.15 mg/kg via IV infusion over 15 minutes, given 30 minutes prior to chemotherapy, may be followed by 2 further doses of 8 mg at 4-hour intervals. Max: 16 mg/dose.
Child: ≥6 months 0.15 mg/kg (Max 8 mg) via IV infusion 30 minutes prior to chemotherapy. May repeat dose at 4 and 8 hours after the initial dose. 
Elderly: <75 years Max: 16 mg via IV infusion over at least 15 minutes; ≥75 years Initially, 8 mg via IV infusion over at least 15 minutes, may be followed by 2 further doses of 8 mg at 4-hour intervals.

Parenteral
Prophylaxis of nausea and vomiting associated with radiation therapy
Adult: 8 mg via slow IV or IM inj immediately before treatment.
Elderly: ≥75 years Max initial dose: 8 mg via IV infusion over 15 minutes, may be followed by 2 further doses of 8 mg at 4-hour intervals.

Rectal
Prevent delayed emesis following chemotherapy
Adult: As supp: 16 mg once daily for up to 5 days after a course of treatment.

Rectal
Nausea and vomiting associated with cancer chemotherapy or radiotherapy
Adult: As supp: 16 mg given 1-2 hours prior to treatment.
Special Patient Group
Pharmacogenomics:

Individuals who have CYP2D6 polymorphism may have altered response to ondansetron, although the reduced enzyme activity in CYP2D6 polymorphism may be normally compensated by other enzymes (CYP3A4, CYP1A2) due to multiple metabolic enzyme pathway.

Genetic testing for CYP2D6 may serve as guide for ondansetron use. However, several factors may cause potential uncertainty of results, including variable allele frequencies among individuals of different ethnicity e.g. CYP2D6*10 is common in Asian population and CYP2D6*17 is common in people with Sub-Saharan African ancestry but has lower prevalence in Caucasians of Europe ancestry. Thus, the alleles that should be tested may vary considerably for a given population.

Ultrarapid metabolisers (carriers of duplicated functional alleles e.g. *1/*1xN, *1/*2xN, *2/*2xN)
May result to increased metabolism of ondansetron leading to reduced antiemetic effect. Select alternative drug not predominantly metabolised by CYP2D6 (e.g. granisetron).

Normal metabolisers (carrying 2 normal function alleles or 2 decreased function alleles or 1 normal function and 1 nonfunctional allele or 1 normal function and 1 decreased function allele or combinations of duplicated alleles that result in an activity score of 1.0–2.0 e.g. *1/*1, *1/*2, *1/*4)
Initiate therapy with recommended starting dose.

Intermediate metabolisers (carriers of 1 decreased function allele e.g. *4/*10, *4/*41) and poor metabolisers (carrriers of nonfunctional alleles only e.g. *3/*4, *4/*4)
Insufficient evidence of demonstrating clinical impact. Initiate therapy with recommended starting dose.
Hepatic Impairment
Moderate to severe: Max: 8 mg daily.
Administration
May be taken with or without food.
Reconstitution
IV infusion: Dilute in 50-100 mL of 5% dextrose in water, 0.9% NaCl or other compatible infusion fluids (e.g. 10% mannitol, Ringer’s solution, 0.3% KCl and 0.9% NaCl, 0.3% KCl and 5% glucose).
Incompatibility
Y-site: Aciclovir, allopurinol, aminophylline, amphotericin B, ampicillin, ampicillin/sulbactam, cefepime, dantrolene, furosemide, ganciclovir, lorazepam, micafungin, pantoprazole, pemetrexed, sargramostim, Na bicarbonate.
Contraindications
Hypersensitivity. Congenital long QT syndrome. Concomitant use with apomorphine.
Special Precautions
Patient with hypokalaemia, hypomagnesaemia, CHF, CV conduction abnormalities, bradyarrhythmia, other conditions that may develop prolongation of QT interval or electrolyte abnormalities, phenylketonuria, subacute intestinal obstruction and abdominal surgery. May mask progressive ileus or gastric distension, and occult bleeding in adenotonsillar surgery. Moderate to severe hepatic impairment. Elderly and children. Pregnancy and lactation.
Adverse Reactions
Significant: Chest pain, bradycardia, hypotension, arrhythmia, hypoxia, transient elevation of liver enzymes, transient blurred vision (due to rapid IV inj). Rarely, transient blindness, extrapyramidal symptoms (e.g. dystonic reactions, oculogyric crisis, dyskinesia), seizures, toxic epidermal necrolysis, serotonin syndrome.
Gastrointestinal disorders: Constipation, diarrhoea, hiccup, xerostomia, dyspepsia.
General disorders and admin site conditions: Malaise, fatigue, fever, cold sensation, injection site reaction, local burning sensation following supp insertion.
Investigations: ECG changes.
Nervous system disorders: Headache, dizziness, sedation, drowsiness, paraesthesia.
Psychiatric disorders: Insomnia, anxiety.
Renal and urinary disorders: Urinary retention.
Reproductive system and breast disorders: Gynaecological disease.
Skin and subcutaneous tissue disorders: Rash, pruritus.
Vascular disorders: Flushing, syncope.
Potentially Fatal: QT interval prolongation, torsade de pointes. Rarely, liver failure, anaphylaxis and bronchospasm.
IV/Parenteral/PO/Rectal: B (Avoid during 1st trimester due to small increase risk of oral cleft defects.)
MonitoringParameters
Monitor ECG, serum K, and serum Mg. Monitor for signs and symptoms of serotonin syndrome and decreased bowel activity.
Overdosage
Symptoms: Hypotension, visual disturbances, severe constipation, vasovagal episode with transient 2nd degree AV block, and serotonin syndrome characterised by vomiting, diarrhoea, agitation, tachycardia, tremor, seizure, delirium and coma in children.  Management: Supportive and symptomatic treatment.
Drug Interactions
Dexamethasone Na phosphate may potentiate antiemetic effect. May develop serotonin syndrome (including altered mental status, autonomic instability, neuromuscular abnormalities) with SSRIs, MAOIs, mirtazapine, fentanyl, lithium, methylene blue, serotonin noradrenaline reuptake inhibitors (SNRIs). Potent CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampicin) may reduce plasma concentrations and increase clearance of ondansetron. Coadministration with antiarrhythmics (e.g. amiodarone), atenolol, anthracyclines (e.g. doxorubicin, daunorubicin), trastuzumab, erythromycin, and ketoconazole may cause additive prolongation of QT interval and increase risk of arrhythmia. May decrease analgesic effect of tramadol.
Potentially Fatal: Concomitant use with apomorphine may result to profound hypotension and loss of consciousness.
Food Interaction
Slightly enhanced extent of absorption with food (tab).
Action
Description: Ondansetron selectively antagonises 5-HT3-receptor on both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone.
Onset: Approx 30 minutes.
Pharmacokinetics:
Absorption: Passively and completely absorbed from the gastrointestinal tract. Slightly enhanced bioavailability with food. Bioavailability: Approx 55-60% (tab). Time to peak plasma concentration: Approx 1.5-2 hours (oral); Approx 10 minutes (IM); Approx 6 hours (rectal).
Distribution: Extensively distributed in the body, including erythrocytes. Crosses placenta. Volume of distribution: 1.9 L/kg. Plasma protein binding: Approx 70-76%.
Metabolism: Extensively metabolised in the liver mainly via hydroxylation, followed by glucuronide or sulfate conjugation by CYP3A4, CYP1A2 and CYP2D6 isoenzymes. Demethylation may also occur.
Excretion: Via urine (44-60%, as metabolites; approx 5% as unchanged drug); faeces (approx 25%). Elimination half-life: Approx 3-6 hours (oral/parenteral); Approx 6 hours (rectal).
Chemical Structure

Chemical Structure Image
Ondansetron

Source: National Center for Biotechnology Information. PubChem Database. Ondansetron, CID=4595, https://pubchem.ncbi.nlm.nih.gov/compound/Ondansetron (accessed on Jan. 22, 2020)

Storage
Tab: Store between 2-30°C. Oral soluble film: Store between 20-25°C. Protect from moisture. Oral solution, syr: Store between 15-30°C. Protect from light. Do not refrigerate. Supp: Store below 30°C. Vial: Store between 2-30°C. Protect from light.
ATC Classification
A04AA01 - ondansetron ; Belongs to the class of serotonin (5HT3) antagonists. Used for the prevention of nausea and vomiting.
References
Bell GC, Caudle KE, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron. CPIC Guidelines. 2017 Aug;102(2):213-218. doi: 10.1002/cpt.598. Accessed 18/03/2019

Bell GC, Caudle KE, Whirl-Carrillo M, et al. Supplement to: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron. CPIC Guideline. Accessed 18/03/2019

Anon. Ondansetron Hydrochloride. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 18/03/2019.

Anon. Ondansetron. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 18/03/2019.

Aurobindo Pharma NZ Limited. Auro-Ondansetron Film-coated Tablet data sheet 29 August 2013. Medsafe. http://www.medsafe.govt.nz/. Accessed 18/03/2019.

Buckingham R (ed). Ondansetron. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 18/03/2019.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org/. Accessed 18/03/2019.

Ondansetron Hydrochloride Solution (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 18/03/2019.

Ondansetron Tablet, Film Coated (Sandoz Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 18/03/2019.

Ondansetron Tablet, Orally Disintegrating (Aidarex Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 18/03/2019.

Zofran Suppositories 16 mg (Novartis Pharmaceuticals UK Ltd). MHRA. https://products.mhra.gov.uk/. Accessed 18/03/2019.

Disclaimer: This information is independently developed by MIMS based on Ondansetron from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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