Zofra ODT Dispersible Tablet

Zofra ODT is a serotonin subtype 3 (5-HT3) receptor antagonist indicated:

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

Zofra ODT oral soluble film is a orally dissolving film designed to be applied on top of the tongue where it will dissolve within 20 seconds and then is swallowed with saliva. Oral soluble film does not require water to aid dissolution or swallowing. The active ingredient in Zofra ODT is Zofra ODT base, the racemic form of Zofra ODT, and a selective blocking agent of the serotonin 5-HT3 receptor type. The empirical formula is C₁₈H₁₉N₃O representing a molecular weight of 293.3.

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 emetogenic chemotherapy.
• Moderate emetogenic cancer chemotherapy: 10 ml (8 mg) Ondansetron Oral Solution administered 30 minutes before start of emetogenic chemotherapy. A further 10 ml dose should be administered after 8 hours of the first dose. One 10 ml dose should be administered twice a day (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 the start of chemotherapy. The other 2 doses should be taken 4 and 8 hours after the first dose. Then 5 ml oral solution should be administered 3 times a day (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):

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

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 successively as three 8 mg films 30 minutes before the start of chemotherapy.

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

• Adults and pediatric patients 12 years of age and older: One 8 mg film 30 minutes before chemotherapy followed by an 8 mg dose 8 hours later. Administer one 8 mg film twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.
• Pediatric patients 4 through 11 years of age: One 4 mg film three times a day. Administer the first dose 30 minutes before chemotherapy, with subsequent doses 4 and 8 hours later. Administer one 4 mg film three times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.
• Prevention of nausea and vomiting associated with radiotherapy: The adult dosage is one 8 mg film three times a day.
• Postoperative nausea and vomiting: The adult dose is 16 mg given successively as two 8 mg films 1 hour before anesthesia.

Administration of Oral Soluble Film:

• Step 1: Tear the pouch carefully along with the edge tear mark.
• Step 2: Put the Ondansetron film on top of your tongue. It will dissolve within 20 seconds
• Step 3: Do not chew or swallow the film whole.
• Step 4: Swallow after the Onsaf oral soluble film dissolves. You may swallow the dissolved film with or without liquid.
• Step 5: Wash your hands after taking Onsaf oral soluble film

Zofra ODT does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver. Because Zofra ODT is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance and hence, the half-life of Zofra ODT. On the basis of available data, no dosage adjustment of Ondasetron is recommended for patients on these drugs.

Contraindicated in patients known to have hypersensitivity to the drug or any of its components. Concomitant use of apomorphine.

Frequently reported adverse events were headache, constipation and diarrhea, but the majority have been mild or moderate in nature. In chemotherapy-induced nausea and vomiting, rash has occurred in approximately 1% of patients receiving Zofra ODT. There also have been reports to a sensation of flushing or warmth, hiccups and liver enzyme abnormalities. Rare cases of anaphylaxis, brochospasm, tachycardia, angina (chest pain), hypokalemia, shortness of breath have also been reported, except for bronchospasm and anaphylaxis, the relationship to Zofra ODT is unclear. There have been no evidence to extrapyramidal reactions, in rare case oculogyric crisis appearing alone, as well as with other dystonic reactions without definitive clinical evidence. In case of PONV, with the exception of headache, rates of these events were not significantly different in the Zofra ODT and placebo groups.

Carcinogenic effects were not seen in 2-year studies in rats and mice with oral Ondansetron doses up to 10 and 30 mg/kg per day, respectively. Ondansetron was not mutagenic in standard tests for mutagenicity. Oral administration of Ondansetron up to 15 mg/kg per day did not affect fertility or general reproduction performance of male and female rats.

Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg per day, respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to Ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. Ondansetron is excreted in the breast milk of rats. So caution should be exercised when Ondansetron is administered to a nursing women.

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists. Zofra ODT is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. The use of Zofra ODT in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension.

Dosage Adjustment for Patients With Impaired Renal Function: The dosage recommendation is the same as for the general population.

Dosage Adjustment for Patients With Impaired Hepatic Function: In patients with severe hepatic impairment, a single maximal daily dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended.

4 years of age or younger: Little information is available about dosage in pediatric patients 4 years of age or younger.

Over the age of 65: Dosage adjustment is not needed in patients over the age of 65.

Anti-emetic drugs

Store at temperature not exceeding 30ºC in a dry place. Protect from light and moisture.