- Medicines and Healthcare products Regulatory Agency
- Therapeutic area:
- Anaesthesia and intensive care and Cancer
New specific guidance on dose-dependent prolongation of QTc with ondansetron.
Article date: July 2013
Ondansetron (brand leader Zofran) is indicated for the prevention and treatment of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy, and for the prevention and treatment of postoperative nausea and vomiting.
Prolongation of QTc interval and cardiac arrhythmia, including Torsade de Pointes, are known risks with ondansetron. In the August 2012 issue of Drug Safety Update, we informed you about the results of a study that showed ondansetron causes a dose-dependent prolongation of QTc, and about new recommendations for the maximum single intravenous dose in adults.
Further analyses of the results of this study, together with other data sources, have enabled greater understanding of the relation between dose and risk of QT prolongation. As a result, further specific guidance is available for intravenous ondansetron in relation to:
- repeat dosing in all adults
- dosing for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients age 75 years or older
- dilution and administration for prevention of CINV for patients age 65 years or older
Advice for healthcare professionals
Patients age 75 years or older:
- a single dose of intravenous ondansetron for the prevention of CINV must not exceed 8 mg (infused over at least 15 minutes)
Adult patients younger than 75 years:
- a single dose of intravenous ondansetron for prevention of CINV must not exceed 16 mg (infused over at least 15 minutes)
Dilution and administration in patients age 65 years or older:
- all intravenous doses for prevention of CINV should be diluted in 50–100 mL saline or other compatible fluid and infused over at least 15 minutes
Repeat dosing in all adults (including elderly patients):
- repeat intravenous doses of ondansetron should be given no less than 4 hours apart
Reminder of previous advice (from August 2012)
- 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 QT interval (including cytotoxic drugs) or that may lead to:
- electrolyte abnormalities
- congestive heart failure
- use of medicines that lower heart rate
- hypokalaemia and hypomagnesaemia should be corrected before ondansetron administration
There are no changes to the recommended dosing for ondansetron use in the following settings:
- oral or rectal administration for CINV in any adult (including elderly patients)
- intravenous or oral use for prevention and treatment of postoperative nausea and vomiting in any adult (including elderly patients)—maximum recommended dose in this setting is a single dose of 4 mg
- intravenous or oral use for either indication in children (age >6 months and adolescents)
Remember that you can report suspected side effects to ondansetron on a Yellow Card (www.mhra.gov.uk/yellowcard).
Article citation: Drug Safety Update vol 6 issue 12, July 2013: A3.