Ondansetron: Antiemetic for the prevention and treatment of nausea and vomiting
Ondansetron is a selective serotonin 5-HT3 receptor antagonist belonging to the group of antiemetics. Since its approval in the early 1990s, it has played a central role in the prophylaxis and therapy of chemotherapy-induced, radiotherapy-induced, and post-operative nausea and vomiting. In Germany, the active ingredient is available under the brand name Zofran and numerous generics. Ondansetron is available as tablets, orally dissolving tablets, oral solution, suppositories, and injection solution, allowing flexible use even in patients with severe nausea.
Nausea and vomiting are among the most common and subjectively distressing side effects of chemotherapy or radiotherapy. Ondansetron has considerably improved treatment options in this area and is firmly established as a first-line therapy in clinical guidelines worldwide. In addition, the active ingredient is routinely used in anaesthesiology for the prevention of post-operative nausea and vomiting (PONV).
Mechanism of Action
Ondansetron selectively and competitively blocks 5-HT3 receptors, which are found in both the peripheral and central nervous systems. These receptors are ion channels that, when activated by serotonin (5-hydroxytryptamine), allow the influx of sodium and potassium ions into the cell. In the context of nausea and vomiting, two localisations play a decisive role:
Firstly, 5-HT3 receptors are located on the afferent vagal and splanchnic fibres of the gastrointestinal tract. During chemotherapy or radiotherapy, large amounts of serotonin are released from the enterochromaffin cells of the intestinal mucosa, which activate these receptors and thus transmit vomiting impulses to the vomiting centre in the brainstem. By blocking these peripheral 5-HT3 receptors, ondansetron interrupts this signalling pathway.
Secondly, 5-HT3 receptors are located in the area postrema (vomiting centre) of the brainstem and in the nucleus tractus solitarii. Ondansetron also inhibits these central receptors, thereby dampening the central nervous processing of vomiting impulses. This dual peripheral and central effect explains the pronounced antiemetic efficacy.
Ondansetron barely affects dopaminergic, muscarinic, or histamine receptors, which explains why it causes fewer extrapyramidal side effects and sedation compared to older antiemetics (e.g. metoclopramide).
Indications
- Chemotherapy-induced nausea and vomiting (CINV): Prophylaxis and therapy with highly and moderately emetogenic chemotherapy, both acute (up to 24 hours after chemotherapy) and delayed (days 2 to 5)
- Radiotherapy-induced nausea and vomiting (RINV): Particularly with total body irradiation or abdominal irradiation
- Post-operative nausea and vomiting (PONV): Prophylaxis and therapy in the recovery room after anaesthesia
- Off-label applications: Nausea in pregnancy (hyperemesis gravidarum), nausea in gastroenteritis, cyclic vomiting, pruritus during opioid therapy
Dosage and Application
Adults for CINV (oral): 8 mg 1 to 2 hours before chemotherapy, then 8 mg every 12 hours for 1 to 5 days. Adults for CINV (intravenous): 8 mg as a slow injection or short infusion immediately before chemotherapy, possibly followed by oral continuation. Children from 6 months for CINV: Weight-adapted dosing (up to 10 kg: 5 mg/m2 BSA; from 10 kg: 4 mg as a single dose, max. 8 mg per administration). PONV (adults): 4 mg as a slow intravenous injection at the end of anaesthesia or when symptoms occur. Maximum daily dose: 32 mg oral or 8 mg intravenous; due to QTc concerns, the IV single dose was reduced to 16 mg (older recommendations: 32 mg).
Ondansetron can be taken regardless of meals. Allow orally dissolving tablets to dissolve on the tongue without drinking water. With intravenous administration, the injection should be given slowly over at least 30 seconds to minimise the risk of QTc prolongation. In hepatic insufficiency (Child-Pugh C), the daily dose should be limited to 8 mg.
Side Effects
Very common and common: Headache (up to 20% of patients), constipation, sensation of warmth or flushing after injection, elevated liver enzyme values (usually asymptomatic and reversible).
Occasional: Dizziness (especially after rapid intravenous administration), itching, dry mouth, diarrhoea.
Rare to very rare: QTc prolongation and cardiac arrhythmias (torsades de pointes), particularly with high dosing or intravenous administration; seizures; extrapyramidal reactions (rarer than with metoclopramide); anaphylactic reactions; transient visual disturbances (with intravenous administration); urinary retention; hiccup.
Special note on serotonin syndrome: With concurrent use of other serotonergic substances (SSRIs, SNRIs, MAO inhibitors, tramadol), there is theoretically a risk of serotonin syndrome, which can manifest as agitation, tremor, mydriasis, hyperthermia, and tachycardia.
Interactions
QTc-prolonging medications: Antiarrhythmics (amiodarone, sotalol, flecainide), certain antipsychotics, macrolide antibiotics (clarithromycin, erythromycin), and antidepressants can increase the risk of life-threatening cardiac arrhythmias in combination with ondansetron. Particular caution is required in patients with known QTc prolongation or electrolyte disturbances.
Serotonergic substances: SSRIs (fluoxetine, sertraline), SNRIs (venlafaxine), MAO inhibitors, and tramadol may promote serotonin syndrome; the combination requires close monitoring.
Apomorphine: Concurrent use is contraindicated; combination can lead to pronounced hypotension and loss of consciousness.
Phenytoin, carbamazepine, rifampicin: Enzyme inducers can lower ondansetron levels and reduce efficacy; dose adjustment may be required.
Tramadol: Ondansetron can reduce the analgesic effect of tramadol, as tramadol acts via 5-HT3 receptors.
Special Notes
Pregnancy: Ondansetron is frequently used off-label for hyperemesis gravidarum. More recent data from large studies show no clear malformation risk in the first trimester; however, some individual studies have discussed indications of a slightly increased risk for cleft palate. The benefit-risk assessment should be made individually and after medical consultation. In the product information, ondansetron is not approved during pregnancy; off-label use occurs after careful consideration.
Breastfeeding: Ondansetron passes into breast milk. With short-term use, the risk to the infant is presumably low; however, use during breastfeeding should be discussed with the treating physician.
Cardiac diseases: In patients with congenital QTc prolongation, heart failure, or relevant electrolyte disturbances (hypokalaemia, hypomagnesaemia), an ECG before therapy is recommended. The concurrent administration of other QTc-prolonging substances should be carefully considered.
Hepatic insufficiency: Since ondansetron is predominantly metabolised hepatically (CYP3A4, CYP1A2, CYP2D6), clearance is greatly reduced in severe hepatic insufficiency. The daily dose should not exceed 8 mg.
Frequently Asked Questions
How quickly does ondansetron work?
Ondansetron rapidly exerts its antiemetic effect: after oral ingestion, an effect is noticeable within 30 to 60 minutes; with intravenous administration within a few minutes. It is therefore administered immediately after anaesthesia for PONV and shortly before the start of the infusion for chemotherapy.
Can ondansetron also be used for gastroenteritis?
Yes, ondansetron is frequently used off-label for gastroenteritis, particularly in children, to relieve vomiting and allow fluid intake. It does not eliminate the cause of the illness (viruses or bacteria), but can relieve symptoms and shorten hospital stays.
Is ondansetron a controlled substance?
No, ondansetron is not subject to the Narcotics Act and has no potential for dependence. It is a prescription-only medication prescribed on a normal prescription.
What is the difference between ondansetron and metoclopramide?
Both active ingredients are antiemetics but act through different mechanisms. Metoclopramide primarily blocks dopamine D2 receptors and also has a prokinetic effect on the stomach. Ondansetron acts selectively via 5-HT3 receptors and thus has a more favourable profile regarding extrapyramidal side effects, but without prokinetic effect.
References
- Product information Zofran (GlaxoSmithKline), as of 2024
- Roila F et al.: 2016 MASCC and ESMO guideline update for the prevention of chemotherapy and radiotherapy-induced nausea and vomiting. Annals of Oncology, 2016
- European Medicines Agency (EMA): Zofran EPAR and QTc risk assessment, 2013
- Federal Institute for Drugs and Medical Devices (BfArM): Product information ondansetron generics, 2024
- Trottier ED et al.: Ondansetron in children with gastroenteritis. Canadian Medical Association Journal, 2012