From the Guidelines
Zofran (ondansetron) is generally considered safe for elderly patients when used appropriately, but its use requires careful consideration of potential age-related changes in drug metabolism and elimination, as well as potential interactions with other medications 1.
Key Considerations
- Elderly patients may experience similar side effects to younger adults, including headache, constipation, and occasionally QT interval prolongation, but these effects may be more pronounced due to age-related changes in drug metabolism and elimination 1.
- The standard adult dosing of 4-8 mg taken orally every 8-12 hours as needed for nausea may apply to elderly patients, but dose adjustments may be necessary in patients with liver or kidney impairment 1.
- Elderly patients are more susceptible to the effects of polypharmacy, and Zofran should be used with caution in patients taking other medications that can affect heart rhythm or in those with existing heart conditions 1.
Monitoring and Precautions
- Close monitoring of elderly patients is necessary to minimize the risk of adverse effects, particularly those related to QT interval prolongation and potential interactions with other medications 1.
- Healthcare providers should consult with elderly patients before starting Zofran to ensure appropriate dosing and monitoring, taking into account the patient's medical history, current medications, and potential risk factors for adverse effects 1.
Age-Related Changes in Drug Metabolism and Elimination
- Age-related changes in drug metabolism and elimination, such as decreased liver mass and hepatic blood flow, and decreased renal function, can affect the pharmacokinetics of Zofran in elderly patients 1.
- These changes may lead to increased exposure to the drug and a higher risk of adverse effects, emphasizing the need for careful dose selection and monitoring in elderly patients 1.
From the FDA Drug Label
Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US-and foreign-controlled clinical trials, for which there were subgroup analyses, 938 (19%) were aged 65 years and older. No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger subjects A reduction in clearance and increase in elimination half-life were seen in patients older than 75 years compared with younger subjects [see Clinical Pharmacology (12. 3)]. There were an insufficient number of patients older than 75 years of age and older in the clinical trials to permit safety or efficacy conclusions in this age-group. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustment is needed in elderly patients.
Safety in the Elderly: Ondansetron is considered safe in elderly patients, with no overall differences in safety or effectiveness observed between subjects 65 years of age and older and younger subjects 2. However, a reduction in clearance and increase in elimination half-life were seen in patients older than 75 years compared with younger subjects.
- Key Points:
- No dosage adjustment is needed in elderly patients.
- Greater sensitivity of some older individuals cannot be ruled out.
- Clinical experience has not identified differences in responses between the elderly and younger patients.
From the Research
Safety of Zofran in the Elderly
- The safety of Zofran (ondansetron) in the elderly is a concern due to its potential to prolong the QT interval, which can increase the risk of torsades de pointes and other cardiac arrhythmias 3, 4.
- A meta-analysis of 10 studies found that ondansetron was associated with a statistically significant prevalence of QT prolongation in all age groups, including patients older than 50 years 3.
- A prospective, observational study found that intravenous ondansetron prolonged the QTc interval by 19.3 ± 18 msec in hospitalized patients with cardiovascular disease and additional risk factors for torsades de pointes 4.
- Another study found that a single dose of 4 mg of intravenous ondansetron was associated with a mean QTc increase of 16.2 msec in emergency department patients 5.
Risk Factors for QT Prolongation
- The risk of QT prolongation with ondansetron is higher in patients with cardiovascular disease, such as heart failure or acute coronary syndromes, and those with additional risk factors for torsades de pointes 4.
- The use of other medications that can prolong the QT interval, such as antiarrhythmics or antipsychotics, can increase the risk of QT prolongation with ondansetron 5.
Comparison with Other Medications
- A study on the safety of clozapine in the elderly found that the risk/benefit ratio of clozapine is higher in the elderly due to a greater incidence of side effects, such as leukopenia and agranulocytosis 6.
- In contrast, ondansetron has been found to be effective in preventing postoperative nausea and vomiting with minimal QT prolongation at lower doses, such as 1 mg 7.