Ondansetron (Zofran): important new intravenous dose restriction
- Medicines and Healthcare products Regulatory Agency
- 20 August 2012
- Therapeutic area:
- Anaesthesia and intensive care and GI, hepatology and pancreatic disorders
New maximum single intravenous dose of ondansetron for the management of chemotherapy-induced nausea and vomiting (CINV) restricted due to risk of QTc prolongation.
Article date: August 2012
Ondansetron is indicated for the prevention and treatment of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy, and for the prevention and treatment of post-operative nausea and vomiting.
In a study in healthy adults, ondansetron 32 mg given intravenously (IV) over 15 minutes caused a maximum mean QTc prolongation of 19.57 (upper 90% confidence interval 21.49) milliseconds. This dose may therefore result in a clinically significant degree of QT prolongation in certain individuals.
Ondansetron 8 mg IV over 15 minutes caused a QTc prolongation of 5.84 (upper 90% CI 7.76) milliseconds – this level of prolongation is not usually associated with increased risk of cardiac arrhythmias.
Extrapolating from these results it was predicted that ondansetron 16 mg IV over 15 minutes would cause a QTC prolongation of 9.1 (upper 95% CI 11.2) milliseconds, an extent that is not usually associated with increased risk of cardiac arrhythmias.
Prolongation of the QTc can lead to Torsade de Pointes (TdP), a potentially life-threatening cardiac arrhythmia. Although no cases of TdP were observed in the study, TdP has been reported in association with the use of ondansetron in clinical practice.
Advice to healthcare professionals:
- a single dose of intravenous ondansetron given for the management of chemotherapy-induced nausea and vomiting in adults must not exceed 16 mg (infused over at least 15 minutes)
- ondansetron should be avoided in patients with congenital long QT syndrome
- caution must be used if administering ondansetron to patients with risk factors for QT interval prolongation or cardiac arrhythmias. These include: electrolyte abnormalities; use of other medicines that prolong the QT interval (including cytotoxic drugs) or may lead to electrolyte abnormalities; congestive heart failure; bradyarrhythmias; and use of medicines which lower the heart rate
- hypokalemia and hypomagnesemia should be corrected prior to ondansetron administration
The maximum recommended intravenous dose of ondansetron for the prevention and treatment of post-operative nausea and vomiting in adult patients is a single dose of 4mg and this has not changed. In addition there are no changes in the recommended intravenous dosing for any indication in paediatric patients.
There are no changes to the recommended dosing for oral or rectal ondansetron formulations in adult or paediatric patients in any indication.
BNF section 4.6: Drugs used in nausea and vertigo
Article citation: Drug safety Update August 2012, vol 6 issue 1: A2
Published: 20 August 2012