Ondansetron is a serotonin subtype 3 (5-HT3) receptor antagonist indicated for:

• Prevention of nausea and vomiting associated with initial and repeated courses of emetogenic cancer chemotherapy.
• Prevention and treatment of post-operative nausea and vomiting.
• Prevention of radiotherapy-induced nausea and vomiting.

Ondansetron oral soluble film is an orally dissolving film designed to be placed on top of the tongue, where it dissolves within 20 seconds and is then swallowed with saliva. It does not require water for swallowing or dissolution. The active ingredient is ondansetron base, the racemic form of ondansetron, which is a selective serotonin 5-HT3 receptor antagonist. The empirical formula is C18H19N3O, with a molecular weight of 293.3.

Ondansetron is a potent and highly selective 5-HT3 receptor antagonist. Its exact mechanism in controlling nausea and vomiting is not fully understood. Chemotherapy agents and radiotherapy can cause the release of serotonin (5-HT) in the small intestine, which activates vagal afferent nerves through 5-HT3 receptors and triggers the vomiting reflex. Ondansetron blocks this reflex at its initiation.

Vagal stimulation may also lead to serotonin release in the area postrema in the brain, located on the floor of the fourth ventricle, which can further promote vomiting through a central pathway. Therefore, ondansetron likely works by blocking 5-HT3 receptors in both the peripheral and central nervous systems to control chemotherapy- and radiotherapy-induced nausea and vomiting. The exact mechanism for prevention of post-operative nausea and vomiting is not fully known, but it may involve similar pathways as those in chemotherapy-induced nausea and vomiting.

Chemotherapy-Induced Nausea and Vomiting
Adults, Pediatric patients (6 months to 18 years):

• 8 mg tablet/orodispersible tablet: Three 0.15 mg/kg doses, up to a maximum of 16 mg per dose.
• 4 mg orodispersible tablet: Three 0.15 mg/kg doses, up to a maximum of 16 mg per dose.
• Injection: Three 0.15 mg/kg doses, up to a maximum of 16 mg per dose, infused intravenously over 15 minutes.

Radiotherapy-Induced Nausea and Vomiting
Adults:

• 8 mg tablet/orodispersible tablet: Initial dose: 8 mg orally 1 to 2 hours before radiotherapy. Post radiotherapy: 8 mg orally every 8 hours for up to 5 days after a course of treatment.
• 4 mg orodispersible tablet: Three 0.15 mg/kg doses, up to a maximum of 16 mg per dose.
• Injection: Three 0.15 mg/kg doses, up to a maximum of 16 mg per dose, infused intravenously over 15 minutes.

Postoperative Nausea and Vomiting
Adults:

• 8 mg tablet/orodispersible tablet: 16 mg given as two 8 mg tablets.
• 4 mg orodispersible tablet: 16 mg.
• Injection: 4 mg.

Pediatrics (>40 kg): Injection: 4 mg
Pediatrics (40 kg): Injection: 0.1 mg/kg

Chemotherapy-induced Nausea and Vomiting
Adults/Geriatric/Child of 12 years or over:

• Highly emetogenic cancer chemotherapy: 30 ml (24 mg) Ondansetron Oral Solution administered 30 minutes before start of chemotherapy.
• Moderate emetogenic cancer chemotherapy: 10 ml (8 mg) Ondansetron Oral Solution administered 30 minutes before start of chemotherapy. A further 10 ml dose should be given after 8 hours of the first dose. One 10 ml dose should be given twice daily (every 12 hours) for 1–2 days after completion of chemotherapy.

Pediatric (4–11 years): 5 ml (4 mg) Ondansetron Oral Solution should be taken 30 minutes before chemotherapy. The next 2 doses should be taken 4 and 8 hours after the first dose. Then 5 ml oral solution should be given 3 times daily (every 8 hours) for 1–2 days after completion of chemotherapy.

Oral solution:

Radiotherapy induced Nausea and Vomiting (Adults/Geriatric/Child of 12 years or over):

• Recommended oral dosage: 10 ml (8 mg) Ondansetron Oral Solution 3 times daily.
• For total body irradiation: 10 ml (8 mg) should be given 1 to 2 hours before each fraction of radiotherapy each day.
• For single high-dose abdominal radiotherapy: 10 ml should be given 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours for 1–2 days after completion.
• For daily fractionated abdominal radiotherapy: 10 ml should be given 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day of radiotherapy.

Postoperative Nausea and Vomiting (Adults/Geriatric/Child of 12 years or over):

• 20 ml (16 mg) Ondansetron Oral Solution 1 hour before induction of anesthesia.

Oral Soluble Film:

Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy:

• Adult oral dose: 24 mg given as three 8 mg films 30 minutes before chemotherapy.

Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy:

• Adults and pediatric patients 12 years and older: One 8 mg film 30 minutes before chemotherapy followed by an 8 mg dose 8 hours later. Then one 8 mg film twice daily (every 12 hours) for 1–2 days after chemotherapy.
• Pediatric patients 4–11 years: One 4 mg film three times daily. First dose 30 minutes before chemotherapy, second and third doses 4 and 8 hours later. Then one 4 mg film three times daily (every 8 hours) for 1–2 days after chemotherapy.
• Prevention of nausea and vomiting associated with radiotherapy: Adult dose is one 8 mg film three times daily.
• Postoperative nausea and vomiting: Adult dose is 16 mg given as two 8 mg films 1 hour before anesthesia.

Administration of Oral Soluble Film:

• Step 1: Tear the pouch carefully along the edge tear mark.
• Step 2: Place the Ondansetron film on top of the tongue. It will dissolve within 20 seconds.
• Step 3: Do not chew or swallow the film whole.
• Step 4: After dissolution, swallow the film. It may be swallowed with or without liquid.
• Step 5: Wash hands after taking Onsaf oral soluble film.

Ondansetron does not appear to induce or inhibit the cytochrome P450 drug-metabolizing enzyme system in the liver. However, since ondansetron is metabolized by hepatic cytochrome P450 enzymes, drugs that induce or inhibit these enzymes may affect its clearance and half-life. Based on available data, no dose adjustment of ondansetron is recommended when used with these drugs.

It is contraindicated in patients with known hypersensitivity to ondansetron or any of its components. Concomitant use with apomorphine is also contraindicated.

The most commonly reported adverse effects include headache, constipation, and diarrhea, which are usually mild to moderate. In chemotherapy-induced nausea and vomiting, rash occurs in about 1% of patients receiving ondansetron. Other reported effects include flushing or warmth sensation, hiccups, and abnormal liver enzyme levels. Rare cases of anaphylaxis, bronchospasm, tachycardia, angina (chest pain), hypokalemia, and shortness of breath have also been reported. Except for bronchospasm and anaphylaxis, a clear relationship with ondansetron is not established. No consistent evidence of extrapyramidal reactions has been found; in rare cases, oculogyric crisis and other dystonic reactions have been reported without definite clinical confirmation. In post-operative nausea and vomiting, except for headache, these adverse event rates were similar to placebo.

Carcinogenic effects were not observed in 2-year studies in rats and mice at oral doses up to 10 mg/kg/day and 30 mg/kg/day, respectively. Ondansetron was not mutagenic in standard tests. Oral doses up to 15 mg/kg/day did not affect fertility or reproductive performance in male and female rats.

Reproductive studies in pregnant rats and rabbits (up to 15 mg/kg/day and 30 mg/kg/day, respectively) showed no evidence of harm to fertility or the fetus. However, adequate and well-controlled studies in pregnant women are not available. Ondansetron is excreted in the milk of rats; therefore, caution is advised when administering to breastfeeding women.

Hypersensitivity reactions have been reported in patients sensitive to other selective 5-HT3 receptor antagonists. Ondansetron does not stimulate gastric or intestinal motility and should not be used as a substitute for nasogastric suction. In post-operative patients or those receiving chemotherapy, ondansetron may mask progressive ileus and/or gastric distension.

Renal impairment: No dosage adjustment is required.
Hepatic impairment: In severe hepatic impairment, a single maximum daily dose of 8 mg infused over 15 minutes is recommended, starting 30 minutes before chemotherapy.
Children ≤4 years: Limited data available.
Elderly (>65 years): No dosage adjustment required.

Antiemetic drugs.

Store below 30°C in a dry place. Protect from light and moisture.