Apulset

Apulset 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.

Ondansetron is a potent, highly selective 5HT 3 receptor-antagonist. Its precise mode of action in the control of nausea and vomiting is not known. Chemotherapeutic agents and radiotherapy may cause release of 5HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5HT 3 receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism. Thus, the effect of ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of 5HT 3 receptors on neurons located both in the peripheral and central nervous system. The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic 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 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.

Apulset does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver. Because Apulset 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 Apulset. 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 Apulset. 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 Apulset 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 Apulset 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. Apulset is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. The use of Apulset in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension.

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