What is the recommended dose of Zofran (ondansetron) for an adult patient with normal renal function requiring intravenous (IV) administration?

IV Ondansetron Dosing for Adults with Normal Renal Function

For adults with normal renal function, the standard IV ondansetron dose is 4 mg administered undiluted over 2-5 minutes for postoperative nausea and vomiting, or 0.15 mg/kg (maximum 16 mg per dose) diluted and infused over 15 minutes for chemotherapy-induced nausea and vomiting. 1

Dosing by Clinical Indication

Postoperative Nausea and Vomiting (PONV)

• Standard dose: 4 mg IV undiluted, administered immediately before anesthesia induction or postoperatively 1
• No dilution required before administration 1
• For patients weighing >40 kg: 4 mg IV as a single dose 1
• Critical caveat: A second 4 mg dose administered postoperatively in patients who received prophylactic ondansetron provides NO additional benefit 1

Chemotherapy-Induced Nausea and Vomiting (CINV)

• Standard regimen: 0.15 mg/kg per dose (maximum 16 mg per dose) for 3 doses 1
• Must be diluted in 50 mL of 5% Dextrose or 0.9% Sodium Chloride before administration 1
• Infuse over 15 minutes beginning 30 minutes before chemotherapy, then repeat at 4 and 8 hours after the first dose 1

Alternative Single-Dose Regimen for Cisplatin

• 32 mg IV as a single dose is more effective than 8 mg and at least as effective as the three-dose regimen 2
• Dilute in 50 mL and infuse over 15 minutes 1
• This single 32-mg dose achieved complete response (no emesis) in 48% of high-dose cisplatin patients versus 35% with 8 mg (p=0.048) 2

Critical Safety Considerations

QT Prolongation Risk

• The FDA issued a warning specifically for the 32-mg IV dose due to QT interval prolongation risk 3
• The 32-mg dose should only be used for highly emetogenic chemotherapy when benefits outweigh cardiac risks 3
• Lower doses (4-8 mg) appear safer, though one study showed QT prolongation even at lower doses in healthy volunteers 3
• Avoid in patients with congenital long QT syndrome, electrolyte abnormalities (hypokalemia, hypomagnesemia), or concurrent QT-prolonging medications 3

Hepatic Transaminase Elevations

• Transaminase elevations occurred in 6-8% of ondansetron patients receiving cisplatin versus 2% with metoclopramide 4
• The incidence correlated with cisplatin dose, not ondansetron dose—10-fold higher with high-dose cisplatin (≥100 mg/m²) versus medium-dose 2
• With non-cisplatin chemotherapy, no difference in transaminase values versus placebo 4

Preparation and Administration Requirements

For CINV (Dilution Mandatory)

• Dilute in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection 1
• Infuse over 15 minutes 1
• After dilution, do not use beyond 24 hours 1
• Inspect for precipitate before administration; if present at stopper/vial interface, shake vigorously to resolubilize 1
• Do not mix with alkaline solutions as precipitation may occur 1

For PONV (No Dilution Required)

• Administer undiluted 1
• Inspect visually for particulate matter and discoloration; discard if present 1

Comparative Efficacy Data

Versus Metoclopramide

• Ondansetron demonstrated superior antiemetic efficacy with fewer adverse events 5
• Extrapyramidal symptoms occurred in 5% of metoclopramide patients versus 0% with ondansetron 4
• Diarrhea occurred in 29% with metoclopramide versus 15% with ondansetron 4

Adverse Event Profile

• Most common: headache (17-21%), constipation (7%), diarrhea (15%) 4
• Overall adverse event incidence: 45% with IV ondansetron versus 59% with metoclopramide 4
• In pediatric patients, adverse event incidence was only 19%, with headache being most common (4%) 5

Pediatric Dosing Considerations

• For children ≥6 months: 0.15 mg/kg per dose (maximum 16 mg) for CINV, same three-dose schedule as adults 1
• For infants 6 months to 1 year or ≤10 kg: may dilute in 10-50 mL based on fluid needs 1
• For PONV in children ≥1 month and ≤40 kg: 0.1 mg/kg IV (maximum 4 mg) 1
• Ondansetron is well-tolerated in children with a 19% adverse event rate versus 45% in adults 5, 4

Common Prescribing Errors to Avoid

• Do not administer a second 4-mg dose for PONV—it provides zero additional benefit 1
• Do not use the 32-mg dose routinely; reserve only for highly emetogenic chemotherapy 3
• Do not forget mandatory dilution for chemotherapy patients—undiluted administration is only appropriate for PONV 1
• Do not continue ondansetron indefinitely; reassess need after the acute treatment period 6