Intramuscular, Intravenous Postoperative nausea and vomiting
Adult: Prophylaxis: 4 mg given as a single dose via slow IV or IM inj, given 1 hour prior to induction of anaesthesia. Treatment: 4 mg as a single dose via slow IV or IM inj. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Child: ≥1 month 0.1 mg/kg (Max: 4 mg) as a single dose via slow IV inj, given before or after induction of anaesthesia or after surgery. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Intramuscular, Intravenous Prophylaxis of nausea and vomiting associated with radiation therapy
Adult: 8 mg as a single dose via slow IV or IM inj immediately before treatment. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Elderly: 65-74 years Initially, 8mg or 16 mg via IV infusion over 15 minutes; ≥75 years Max initial dose: 8 mg via IV infusion for 15 minutes. All initial doses may be followed by 2 additional doses of 8 mg with at least 4-hour intervals. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Intramuscular, Intravenous Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: Dose regimen must be selected according to the severity of the emetogenic challenge. Less emetogenic chemotherapy: 8 mg as a single dose via slow IV or IM inj immediately before chemotherapy. Alternatively, 0.15 mg/kg via IV infusion over 15 minutes, given 30 minutes before chemotherapy then repeated after 4 and 8 hours from the initial dose for a total of 3 doses. Highly emetogenic chemotherapy: 8 mg as a single dose via slow IV or IM inj immediately before chemotherapy, may be followed either by a 1 mg/hour continuous IV infusion for up to 24 hours or by 2 additional doses of 8 mg via slow IV or IM inj with 4 hour intervals. Max initial dose: 16 mg. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Elderly: 65-74 years Initially, 8 mg or 16 mg via IV infusion over 15 minutes; ≥75 years Max initial dose: 8 mg via IV infusion for 15 minutes. All initial doses may be followed by 2 additional doses of 8 mg with at least 4-hour intervals. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Child: ≥6 months 0.15 mg/kg (Max: 16 mg) via IV infusion over 15 minutes, given 30 minutes before chemotherapy then repeated after 4 and 8 hours from the initial dose for a total of 3 doses. Alternatively, an initial single IV dose of 0.15 mg/kg (based on weight) or 5 mg/m2 (based on BSA) may be given, followed after 12 hours by the corresponding oral dose calculated based on weight or BSA. Max initial dose: 8 mg. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Oral Prophylaxis of postoperative nausea and vomiting
Adult: 16 mg as a single dose given 1 hour prior to induction of anaesthesia. Alternatively, 8 mg as a single dose given 1 hour prior to induction of anaesthesia, followed by 2 additional 8 mg doses at 8 hour intervals. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Oral Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: Dose regimen must be selected according to the severity of the emetogenic challenge. Moderately or less emetogenic chemotherapy: Initially, 8 mg given up to 2 hours before chemotherapy, followed by another 8 mg dose after 8-12 hours. Highly emetogenic chemotherapy: 24 mg as a single dose given 30 minutes before chemotherapy. Alternatively, 24 mg as a single dose given 1-2 hours before chemotherapy in combination with dexamethasone. A subsequent dose of 8 mg 12 hourly may be given for up to 5 days after the first 24 hours of these regimens for protection against prolonged or delayed emesis. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Child: Moderately emetogenic chemotherapy: 4-11 years Initially, 4 mg given 30 minutes before chemotherapy, followed by another 4 mg dose after 4 and 8 hours. A subsequent dose of 4 mg tid may be given for up to 1-2 days after the end of chemotherapy; ≥12-17 years Same as adult dose. Alternatively, the dose may be calculated based on weight or BSA given 12 hours after an initial IV single dose and may be given for up to 5 days: ≥6 months with BSA <0.6 m2 or weighing ≤10 kg: 2 mg 12 hourly; BSA 0.6-1.2 m2 or weighing 10-40 kg: 4 mg 12 hourly; BSA >1.2 m2 or weighing >40 kg: 8 mg 12 hourly. Max daily dose: 32 mg. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Oral Prophylaxis of nausea and vomiting associated with radiation therapy
Adult: Dose regimen must be selected according to the severity of the emetogenic challenge. Initially, 8 mg given up to 2 hours before radiotherapy, followed by another 8 mg dose after 8-12 hours. A subsequent dose of 8 mg 12 hourly may be given for up to 5 days after the first 24 hours for protection against prolonged or delayed emesis. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
What are the brands available for Ondansetron in Hong Kong?
Ondansetron is metabolised by multiple CYP450 enzymes (e.g. CYP1A2, CYP2D6, and CYP3A4). Patients who have CYP2D6 polymorphisms may experience altered responses to ondansetron, particularly in patients who are CYP2D6 ultrarapid metabolisers. Despite the limited evidence to support the recommendations, the quality of the studies promote the robustness of the recommendation, that there is an increased metabolism of ondansetron in CYP2D6 ultrarapid metabolisers. Additionally, the treatment recommendations are provided with the understanding that there are multiple available antiemetics not metabolised by CYPD26. Currently, there are limited studies regarding intermediate and poor CYP2D6 metabolisers to identify the implications for the metabolism of ondansetron and its consequent treatment adjustments; for these patients, therapy may be initiated within the recommended dose.
Although available product information may not reference specific dose adjustments according to CYP2D6 genotype, references still indicate the effect of CYP2D6 polymorphisms in the rate of ondansetron elimination. Current international guidelines recommend that genetic testing may be considered to help identify those at significant risk, to provide the most effective antiemetic therapy.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of December 2016:
Phenotype and Genotype
Implications
Recommendations
CYP2D6 ultrarapid metabolisers
Patients carrying duplications of functional alleles e.g. *1/*1xN, *1/*2xN, *2/*2x (where xN represents the number of CYP2D6 gene copies).
Increased metabolism of ondansetron leading to reduced antiemetic effect.
Use an alternative drug not primarily metabolised by CYP2D6 (e.g. granisetron).
Hepatic Impairment
Moderate to severe: Max: 8 mg daily.
Administration
Ondansetron May be taken with or without food.
Reconstitution
Adult: Dilute doses >8 mg (Max: 16 mg) for IV infusion in 50-100 mL compatible infusion fluids (e.g. NaCl 0.9%, dextrose 5% in water, Ringer's solution, Mannitol 10%). Children: Dilute doses for IV infusion in 25-50 mL compatible infusion fluids (e.g. NaCl 0.9%, dextrose 5% in water, Ringer's solution, Mannitol 10%). Recommendations for dilution may vary among individual products and between countries (refer to specific product guidelines).
Contraindications
Congenital long QT syndrome. Concomitant use with apomorphine.
Special Precautions
Patient with a predisposition for QT interval prolongation (e.g. electrolyte abnormalities, CHF, cardiac rhythm or conduction disturbances, bradyarrhythmia); subacute intestinal obstruction. May mask progressive ileus or gastric distension in patients who had abdominal surgery, and occult bleeding in those who had adenotonsillar surgery. Correct electrolyte abnormalities (e.g. hypomagnesaemia, hypokalaemia) before treatment initiation. The conventional tab, orally disintegrating tab, oral solution, and syrup may be used interchangeably. CYP2D6 ultrarapid metabolisers. Moderate to severe hepatic impairment. Children and the elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Serotonin syndrome, myocardial ischaemia, constipation, severe headache, hypersensitivity reactions (e.g. anaphylaxis, bronchospasm). Rarely, QT interval prolongation, torsades de pointes; intestinal obstruction. Cardiac disorders: Chest pain (with or without ST segment depression), bradycardia, arrhythmia. Gastrointestinal disorders: Constipation, diarrhoea, hiccups. General disorders and administration site conditions: Fever, sensation of warmth; malaise, fatigue (oral); local inj site reactions (e.g. pain, erythema, burning sensation). Investigations: Asymptomatic elevation of LFTs. Nervous system disorders: Headache, dizziness, seizures, movement disorders, extrapyramidal symptoms (e.g. dystonic reactions, oculogyric crisis, dyskinesia); drowsiness, sedation, paraesthesia (IV). Psychiatric disorders: Agitation, anxiety (oral). Renal and urinary disorders: Urinary retention (oral). Reproductive system and breast disorders: Gynaecological disease (oral). Respiratory, thoracic and mediastinal disorders: Hypoxia (oral). Skin and subcutaneous tissue disorders: Pruritus, rash. Vascular disorders: Flushing, hypotension.
IV/Parenteral/PO/Rectal: B (Avoid during 1st trimester due to small increase risk of oral cleft defects.)
Monitoring Parameters
Monitor ECG (if applicable), serum K and Mg levels; bowel activity (patient at risk for intestinal obstruction). Assess for signs and symptoms of hypersensitivity reaction, serotonin syndrome, and myocardial ischaemia.
Overdosage
Symptoms: Hypotension, visual disturbances, severe constipation, vasovagal episode with transient 2nd-degree AV block, prolonged QT interval (dose-dependent), and serotonin syndrome (in children) including agitation, diaphoresis, flushing, hypertension, hyperreflexia, horizontal nystagmus, mydriasis, myoclonic movements, tachycardia, tachypnoea, somnolence and seizure. Management: Supportive and symptomatic treatment. ECG monitoring is recommended.
Drug Interactions
May increase the risk of severe hypotension and loss of consciousness with apomorphine. Increased risk of serotonin syndrome with SSRIs, SNRIs MAOIs, mirtazapine, fentanyl, lithium, methylthioninium chloride. Potent CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampicin) may reduce plasma concentrations and increase clearance of ondansetron. May increase the risk of arrhythmias with antiarrhythmics (e.g. amiodarone), β-blockers (e.g. atenolol, timolol), anthracyclines (e.g. doxorubicin, daunorubicin), trastuzumab, antibiotics (e.g. erythromycin), and antifungals (e.g. ketoconazole). May decrease the analgesic effect of tramadol.
Food Interaction
Slightly increased extent of absorption with food.
Action
Description: Mechanism of Action: Ondansetron, a potent anti-emetic, is a highly selective inhibitor of type 3 serotonin (5-HT3) receptors. Its exact mechanism of action is unknown; however, ondansetron selectively antagonises the 5-HT3-receptor located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone, thereby blocking the release of serotonin and inhibiting the initiation of the vomiting reflex. Onset: Approx 30 minutes. Pharmacokinetics: Absorption: Passively and completely absorbed from the gastrointestinal tract. Slightly enhanced extent of absorption with food. Bioavailability: Approx 50-70% (oral). Time to peak plasma concentration: Approx 2 hours (oral); approx 10 minutes (IM); approx 6 hours (rectal). Distribution: Extensively distributed in the body including erythrocytes. Crosses the placenta. Volume of distribution: 1.9 L/kg. Plasma protein binding: Approx 70-76%. Metabolism: Extensively metabolised in the liver mainly via hydroxylation, then via glucuronide or sulfate conjugation by the CYP3A4, CYP1A2 and CYP2D6 isoenzymes. Undergoes first-pass metabolism; demethylation may also occur. Excretion: Via urine (44-60% as metabolites; approx 5% as unchanged drug); faeces (approx 25%). Elimination half-life: Approx 3 hours (oral/parenteral); Approx 6 hours (rectal).
Chemical Structure
Ondansetron Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4595, Ondansetron. https://pubchem.ncbi.nlm.nih.gov/compound/Ondansetron. Accessed June 25, 2024.
Storage
Conventional tab/orally disintegrating tab/oral solution/oral syrup: Store between 15-30°C. Intact vial: Store below 30°C. Protect the oral solution and intact vial from light. Diluted solution for IV infusion: May be stored at 25°C for up to 24 hours or between 2-8°C for up to 36 hours. Storage recommendations may vary among countries and individual products (refer to specific product guidelines).
Bell G, Caudle K, Whirl‐Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron. Clinical Pharmacology and Therapeutics. 2017;102(2):213-218. doi: 10.1002/cpt.598. Accessed 02/05/2024AFT Pharmaceuticals Ltd. Ondansetron-AFT 4 mg/2 mL and 8 mg/4 mL Solution for Injection data sheet 19 July 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 02/05/2024.Annotation of CPIC Guideline for Ondansetron and CYP2D6. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 02/05/2024.Anon. Ondansetron Hydrochloride. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/05/2024.Buckingham R (ed). Ondansetron. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/05/2024.Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org. Accessed 02/05/2024.CYP2D6 - Ondansetron. UpToDate Lexidrug, Pharmacogenomics Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 02/05/2024.IPCA Pharma (NZ) Pty Limited. Periset 4 mg and 8 mg Tablets data sheet 24 February 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 02/05/2024.IPCA Pharma (NZ) Pty Limited. Periset ODT 4 mg and 8 mg Orodispersible Tablets data sheet 21 February 2024. Medsafe. http://www.medsafe.govt.nz. Accessed 02/05/2024.Joint Formulary Committee. Ondansetron. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/05/2024.Ondansetron 2 mg/mL Solution for Injection (Noridem Enterprises Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2024.Ondansetron 4 mg Tablets (Relonchem Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2024.Ondansetron 8 mg Orodispersible Tablets (Syri Limited trading as Syrimed). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2024.Ondansetron 8 mg/5 mL Oral Solution (Rosemont Pharmaceuticals Ltd). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2024.Ondansetron Hydrochloride Solution (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/05/2024.Ondansetron Hydrochloride Tablet, Film Coated (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/05/2024.Ondansetron Injection (Hikma Pharmaceuticals USA Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/05/2024.Ondansetron Tablet, Orally Disintegrating (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/05/2024.Ondansetron. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 02/05/2024.Paediatric Formulary Committee. Ondansetron. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 02/05/2024.Zofran 4 mg and 8 mg Tablets (Sandoz Products Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/05/2024.Zofran 4mg in 2mL Solution for Injection (Sandoz Products Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/05/2024.
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