General Information

Zofran (ondansetron, ondansetron hydrochloride) is a 5-HT3 receptor antagonist.

Zofran is specifically indicated for:

• nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2 .
• nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. (
• nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen
• postoperative nausea and/or vomiting

Zofran is supplied as tablets, orally disintegrating tablets and oral solution. The recommended dosage regimens for adult and pediatric patients are described in the table below. Corresponding doses of Zofran tablets, Zofran ODT orally disintegrating tablets and Zofran oral solution may be used interchangeably. 

Adult Recommended Dosage Regimen for Prevention of Nausea and Vomiting

Pediatric Recommended Dosage Regimen for Prevention of Nausea and Vomiting

Mechanism of Action

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron’s antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT3 receptors and initiate the vomiting reflex.

Side Effects

Adverse effects associated with the use of Zofran may include, but are not limited to, the following:

the prevention of chemotherapy-induced nausea and vomiting:

• headache
• malaise/fatigue
• constipation
• diarrhea

the prevention of radiation-induced nausea and vomiting

• headache
• constipation
• diarrhea

the prevention of postoperative nausea and vomiting

• headache
• hypoxia

Clinical Trial Results

Highly Emetogenic Chemotherapy

In 2 randomized, double-blind, monotherapy trials, a single 24-mg oral dose of Zofran was superior to a relevant historical placebo control in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy. More than 90% of patients receiving a cisplatin dose greater than or equal to 50 mg/m2 in the historical-placebo comparator, experienced vomiting in the absence of antiemetic therapy. The first trial compared oral doses of ondansetron 24 mg as a single dose, 8 mg every 8 hours for 2 doses, and 32 mg as a single dose in 357 adult cancer patients receiving chemotherapy regimens containing cisplatin greater than or equal to 50 mg/m2 . The first or single dose was administered 30 minutes prior to chemotherapy. A total of 66% of patients in the ondansetron 24-mg once-a-day group, 55% in the ondansetron 8-mg twice-a day group, and 55% in the ondansetron 32-mg once-a-day group, completed the 24-hour trial period with 0 emetic episodes and no rescue antiemetic medications, the primary endpoint of efficacy. Each of the 3 treatment groups was shown to be statistically significantly superior to a historical placebo control. In the same trial, 56% of patients receiving a single 24-mg oral dose of ondansetron experienced no nausea during the 24-hour trial period, compared with 36% of patients in the oral ondansetron 8-mg twice-a-day group (P = 0.001) and 50% in the oral ondansetron 32-mg once-a-day group. Dosage regimens of Zofran 8 mg twice daily and 32 mg once daily are not recommended for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy. In a second trial, efficacy of a single 24-mg oral dose of Zofran for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2 , was confirmed.

Moderately Emetogenic Chemotherapy

A randomized, placebo-controlled, double-blind trial was conducted in the US in 67 patients receiving a cyclophosphamide-based chemotherapy regimen containing doxorubicin. The first 8-mg dose of Zofran was administered 30 minutes before the start of chemotherapy, with a subsequent dose 8 hours after the first dose, followed by 8 mg of Zofran twice a day for 2 days after the completion of chemotherapy. Zofran was significantly more effective than placebo in preventing vomiting.

In a double-blind, US trial in 336 patients receiving a cyclophosphamide-based chemotherapy regimen containing either methotrexate or doxorubicin, Zofran 8 mg administered twice a day, was as effective as Zofran 8 mg administered 3 times a day in preventing nausea and vomiting. Zofran 8 mg three times daily is not a recommended regimen for the treatment of moderately emetogenic chemotherapy.

Re-treatment: In single-arm trials, 148 patients receiving cyclophosphamide-based chemotherapy were re-treated with Zofran 8 mg three times daily during subsequent chemotherapy for a total of 396 re-treatment courses. No emetic episodes occurred in 314 (79%) of the re-treatment courses, and only 1 to 2 emetic episodes occurred in 43 (11%) of the re-treatment courses.

Pediatric Trials: Three open-label, single-arm, non-US trials have been performed with 182 pediatric patients aged 4 to 18 years with cancer who were given a variety of cisplatin or noncisplatin regimens. The initial dose of Zofran injection ranged from 0.04 to 0.87 mg per kg (total dose of 2.16 mg to 12 mg) followed by the administration of oral doses of Zofran ranging from 4 to 24 mg daily for 3 days. In these trials, 58% of the 170 evaluable patients had a complete response (no emetic episodes) on Day 1. In 2 trials, the response rates to Zofran 4 mg three times a day in patients younger than 12 years was similar to Zofran 8 mg three times daily in patients 12 to 18 years. Prevention of emesis in these pediatric patients was essentially the same as for adults.

Radiation-Induced Nausea and Vomiting

Total Body Irradiation

In a randomized, placebo-controlled, double-blind trial in 20 patients, 8 mg of Zofran administered 1.5 hours before each fraction of radiotherapy for 4 days was significantly more effective than placebo in preventing vomiting induced by total body irradiation. Total body irradiation consisted of 11 fractions (120 cGy per fraction) over 4 days for a total of 1,320 cGy. Patients received 3 fractions for 3 days, then 2 fractions on Day 4.

Single High-Dose Fraction Radiotherapy

In an active-controlled, double-blind trial in 105 patients receiving single high-dose radiotherapy (800 to 1,000 cGy) over an anterior or posterior field size of greater than or equal to 80 cm2 to the abdomen, Zofran was significantly more effective than metoclopramide with respect to complete control of emesis (0 emetic episodes). Patients received the first dose of Zofran (8 mg) or metoclopramide (10 mg) 1 to 2 hours before radiotherapy. If radiotherapy was given in the morning, 8 mg of Zofran or 10 mg of metoclopramide was administered in the late afternoon and repeated again before bedtime. If radiotherapy was given in the afternoon, patients took 8 mg of Zofran or 10 mg of metoclopramide only once before bedtime. Patients continued the doses of oral medication three times daily for 3 days.

Daily Fractionated Radiotherapy

In an active-controlled, double-blind trial in 135 patients receiving a 1- to 4- week course of fractionated radiotherapy (180 cGy doses) over a field size of greater than or equal to 100 cm2 to the abdomen, Zofran was significantly more effective than prochlorperazine with respect to complete control of emesis (0 emetic episodes). Patients received the first dose of Zofran (8 mg) or prochlorperazine (10 mg) 1 to 2 hours before the first daily radiotherapy fraction, with subsequent 8-mg doses approximately every 8 hours on each day of radiotherapy.

Postoperative Nausea and Vomiting

In 2 placebo-controlled, double-blind trials (one conducted in the US and the other outside the US) in 865 females undergoing inpatient surgical procedures, Zofran 16 mg as a single dose or placebo was administered one hour before the induction of general balanced anesthesia (barbiturate, opioid, nitrous oxide, neuromuscular blockade, and supplemental isoflurane or enflurane), Zofran tablets was significantly more effective than placebo in preventing postoperative nausea and vomiting.