Should ondansetron (Zofran) be taken before or at the same time as oseltamivir (Tamiflu) to prevent vomiting?

Timing of Ondansetron (Zofran) with Oseltamivir (Tamiflu)

Take ondansetron 30 minutes before oseltamivir to prevent vomiting, as this allows the antiemetic to reach peak plasma concentration and establish its effect before the nausea-inducing medication is administered.

Pharmacokinetic Rationale

• Ondansetron reaches peak plasma concentration approximately 1 hour after oral administration, with an onset of antiemetic effect beginning around 30 minutes post-dose 1
• The drug should be administered at least 30 minutes before the emetic stimulus to establish adequate receptor blockade 1
• Ondansetron has a bioavailability of approximately 60% and does not require food for absorption 1

Oseltamivir's Emetic Profile

• Nausea and vomiting are the most common adverse effects of oseltamivir, occurring in approximately 10% (nausea) and 8-9% (vomiting) of adults, and 14-16% (vomiting) in children 2, 3, 4
• Taking oseltamivir with food significantly reduces the severity of nausea and vomiting 2, 3, 4
• Only approximately 1% of patients discontinue oseltamivir due to gastrointestinal side effects 2, 3, 4

Recommended Administration Strategy

Step 1: Administer ondansetron first

• Give ondansetron 8 mg orally (or 4 mg in children 4-11 years, weight-based dosing for younger children) 2
• Wait 30 minutes to allow ondansetron to reach therapeutic levels 1

Step 2: Administer oseltamivir with food

• After the 30-minute interval, give oseltamivir with a meal or substantial snack 2, 3, 4
• The combination of prophylactic ondansetron plus food administration provides dual protection against emesis 2, 4

Step 3: Scheduled ondansetron dosing

• Continue ondansetron 8 mg every 8 hours (scheduled, not as-needed) for the first 24-48 hours of oseltamivir therapy 2
• This maintains consistent antiemetic coverage during the period of highest emetic risk 2

Clinical Evidence Supporting Prophylactic Antiemetic Use

• In IL-2 therapy protocols where nausea is anticipated, scheduled ondansetron 8 mg IV every 8 hours is administered 30 minutes prior to each dose rather than waiting for symptoms to develop 2
• Ondansetron has demonstrated superior efficacy compared to placebo in preventing vomiting in pediatric patients, with significantly lower rates of treatment failure 5
• When used prophylactically in gastroenteritis, ondansetron reduced the need for IV fluid therapy and hospital admission 5

Important Clinical Caveats

• Do not wait for vomiting to occur before administering ondansetron - prophylactic use is more effective than rescue therapy 2, 5
• The increased diarrhea observed with ondansetron in gastroenteritis studies 5 is not a contraindication here, as oseltamivir itself causes minimal diarrhea (<5%) 2
• If vomiting occurs despite prophylactic ondansetron, consider alternative antiemetics (prochlorperazine 10 mg every 6 hours or lorazepam 0.5 mg every 6 hours) 2
• In pregnant women, this same strategy applies - ondansetron 30 minutes before oseltamivir with food, as pregnancy is not a contraindication to either medication and influenza poses significant maternal-fetal risks 4, 6

Alternative Approach if Ondansetron Unavailable

• Administer oseltamivir with a substantial meal to maximize tolerability 2, 3, 4
• Consider prochlorperazine or metoclopramide as alternative antiemetics, though these have higher rates of side effects 7, 5
• The vast majority (99%) of patients tolerate oseltamivir without requiring antiemetic therapy 2, 3