Ondansetron (Zofran) Use in ESRD Patients on Dialysis
Ondansetron is NOT contraindicated in ESRD patients on dialysis and can be safely used without dose adjustment, though plasma clearance is reduced by approximately 50% in severe renal impairment. 1
FDA-Approved Dosing and Pharmacokinetics
The FDA label explicitly states that renal impairment is not expected to significantly influence total clearance of ondansetron, as renal clearance represents only 5% of overall clearance 1
In patients with severe renal impairment (creatinine clearance <30 mL/min), mean plasma clearance is reduced by approximately 50%, but this reduction is variable and not consistently associated with increased half-life 1
No specific dose adjustment is recommended in the FDA labeling for ESRD patients on dialysis 1
Clinical Evidence Supporting Safety and Efficacy
A double-blind crossover study in 10 uremic patients demonstrated that ondansetron 8 mg IV was approximately twice as effective as metoclopramide 10 mg IV for controlling uremia-induced nausea and vomiting (objective score: 2.80 vs 1.40, p<0.005; subjective score: 4.10 vs 2.10, p<0.005) 2
The study confirmed ondansetron's safety profile in uremic patients without reporting significant adverse effects related to renal dysfunction 2
Metabolic Considerations
Ondansetron undergoes extensive hepatic metabolism via multiple cytochrome P-450 enzymes (CYP1A2, CYP2D6, CYP3A4), with only approximately 5% recovered unchanged in urine 1
The multiplicity of metabolic pathways provides redundancy, meaning that loss of one enzyme pathway is compensated by others, resulting in minimal change in overall elimination rates 1
Because elimination is primarily hepatic rather than renal, dialysis does not significantly remove ondansetron and supplemental dosing post-dialysis is not required 1
Practical Dosing Recommendations
Standard adult dosing of ondansetron 4-8 mg IV/PO every 8 hours can be used in ESRD patients on dialysis 1, 2
Timing relative to dialysis sessions is not clinically relevant given the minimal renal clearance 1
Monitor for QT prolongation, which is a class effect of 5-HT3 antagonists, though this risk is not specifically increased by renal impairment 1
Key Clinical Pitfalls to Avoid
Do not withhold ondansetron based on concerns about renal clearance - the drug's predominantly hepatic metabolism makes it safe in ESRD 1
Avoid confusing ondansetron with renally-cleared antiemetics that do require dose adjustment in ESRD 3
Do not provide supplemental doses after dialysis, as dialytic clearance is negligible 1