ONZET

ONZET 8 mg

Film – Coated Tablet

 (Ondansetron)

 

ANTIEMETIC

Category:

Description

The Cathay Drug Co., Inc.

 

FORMULATION

Each film-coated tablet contains:

Ondansetron hydrochloride dihydrate

eq to ondansetron ………………………………… 8 mg

Excipients ………………………………………….. q.s.

Colour: Titanium dioxide, BP

 

PHARMACODYNAMIC PROPERTIES

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 receptor type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zome 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 enterchromaffin cells of the small intestine. In humans, urinary 5-HIAA (5-hydroxyindoleacetic acid) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferent through the 5-HT3 receptors and initiate the vomiting reflex.

 

PHARMACOKINETIC PROPERTIES

Ondansetron is well absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. Mean bioavailability in healthy subjects, following administration of a single 8 mg tablet is approximately 56%.

 

Ondansetron is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the patent compound from the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucoronide or sulphate conjugation. Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of Ondansetron.

 

A reduction in clearance and increase in elimination half-life are seen in patients over 75 years of age. In clinical trials with patients, safety and efficacy were similar in patients over 65 years of age and those under 65 years of age; there was an insufficient number of patients over 75 years of age to permit conclusions in that age-group. No dosage adjustment is recommended in the elderly.

 

In patients with mild to moderate hepatic impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours compared to 5.7 hours in normals. In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced 2-fold to 3-fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours. In patients with severe hepatic impairment, a total daily dose of 8 mg should not be exceeded.

 

Due to the very small contribution (5%) of clearance to the overall clearance, renal impairment was not expected to significantly influence the total clearance of ondansetron. However, ondansetron oral mean plasma clearance was reduced by about 50% in patients with severe renal impairment (CrCl < 30 mL/min). This reduction in clearance is varable and was not consistent with an increase in half-life. No reduction in dose or dosing frequency in these patients is warranted.

 

Plasma protein binding of ondansetron as measured in vitro was 70% to 76% over the concentration range of 10 to 500 ng/mL. Circulating drug also distributes into erythrocytes.

 

INDICATIONS

  1. Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin > 50 mg/m2.
  2. Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
  3. Prevention of 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.
  4. Prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, ondansetron hydrochloride tablets are recommended even where the incidence of postoperative nausea and vomiting is low.

 

DOSAGE AND ADMINISTRATION

Prevention of Nausea and Vomiting Associated with highly emetogenic cancer chemotherapy

The recommended adult dosage of ondansetron hydrochloride is 24 mg given as three 8 mg tablets administered 30 minutes before the start of single day highly emetogenic chemotherapy, including cisplatin > 50 mg/m2 . Multiday, single dose administration of a 24 mg dosage has not been studied.

 

Paediatric Use

There is no experience with the use of a 24 mg dosage in paediatric patients.

 

Geriatric Use

The dosage recommendation is the same as for the general population.

 

 

Prevention of Nausea and Vomiting Associated with moderately emetogenic cancer chemotherapy

The recommended adult oral dosage is one 8 mg ondansetron hydrochloride tablet. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8 mg ondansetron hydrochloride should be administered twice a day (every 12 hours) for 1 to 2 days after completion of therapy.

 

Paediatric Use

For paediatric patients 12 years and older, the dosage is one 8 mg ondansetron hydrochloride tablet. For paediatric patients 4 through 11 years of age, the dosage is one 4 mg ondansetron hydrochloride tablet given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 4 mg tablet ondansetron hydrochloride tablet should be administered 3 times a day for 1 to 2 days after completion of chemotherapy.

 

Geriatric Use

The dosage is the same as for the general population.

 

Prevention of Nausea and Vomiting Associated with radiotherapy, either total body irradiation or single high-dose fraction or daily fractions to the abdomen

The recommended dosage is one 8 mg ondansetron hydrochloride tablet given 3 times daily.

 

  • For total body irradiation, one 8 mg ondansetron hydrochloride tablet given 1 to 2 hours before radiotherapy with subsequent doses every 8 hours after the firstdose for 1 to 2 days after completion of radiotherapy.
  • For single high-dose fraction radiotherapy to the abdomen, one 8 mg ondansetron hydrochloride tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose 1 to 2 hours after completion of radiotherapy.
  • For daily fractionated radiotherapy to the abdomen, one 8 mg ondansetron hydrochloride tablet 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.

Paediatric Use

There is no experience with the use of ondansetron hydrochloride tablet in the prevention of radiation-induced nausea and vomiting in paediatric patients.

 

Geriatric Use

The dosage is the same as for the general population.

 

Postoperative Nausea and Vomiting

The recommended dosage is 16 mg given as two 8 mg ondansetron hydrochloride tablets 1 hour before induction of anesthesia.

 

Paediatric Use

There is no experience with the use of ondansetron hydrochloride tablet in the prevention of postoperative nausea and vomiting in paediatric patients.

 

Geriatric Use

The dosage is the same as for the general population.

 

Dosage adjustment for patients with Impaired Renal Function

The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.

 

Dosage adjustment for patients with Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), 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. Or as prescribed by the physician.

 

CONTRAINDICATIONS

Ondansetron tablets are contraindicated to patients known to have hypersensitivity of the drug.

WARNINGS

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.

 

DRUG INTERACTIONS

Ondansetron does not itself appear to induce or inhibit the cytochrome P450 drug metabolizing enzyme system of the liver. Because ondansetron is metabolized by hepatic cytochrome P450 drug metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers or inhibitors of these enzymes may change the clearance and hence, the half-life of ondansetron. On the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs.

Phenytoin, carbamazepine and rifampicin

In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine and rifampicin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. However, no dosage adjustment for ondansetron is recommended.

 

Tramadol

Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small studies indicate that ondansetron may be associated with an increase in patient controlled administration of tramadol.

 

Chemotherapy

In humans, carmustine, etoposide and cisplatin do not affect the pharmacokinetics of ondansetron.

 

Use in surgical patients

The co-administration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.

 

ADVERSE EFFECTS

The following frequencies are estimated at the standard doses of ondansetron according to indication and formulation.

  • Immune system disorders

Rare: Immediate hypersensitivity reactions sometimes severe, including anaphylaxis.

 

  • Nervous system disorders

Very common: headache

Uncommon: seizures, movement disorders (including extrapyramidal reactions such as dystonic reactions, oculogyric crisis and dyskinesia.

Rare: dizziness during rapid IV administration

 

  • Eye disorders

Rare: transient visual disturbances predominantly during IV administration

Very rare: transient blindness predominantly during IV administration.

 

  • Cardiac disorders

Uncommon: arrhythmias, chest pain with or without ST segment depression, bradycardia

 

  • Vascular disorders

Common: sensation of warmth or flushing

Uncommon: hypotension

 

  • Respiratory, thoracic and mediastinal disorders

Uncommon: Hiccups

 

  • Gastrointestinal disorders

Common: constipation

 

  • Hepatobiliary disorders

Uncommon: asymptomatic increases in liver function tests.

 

  • Vascular disorders

Common: sensation of warmth or flushing

Uncommon: hypotension

 

  • Respiratory, thoracic and mediastinal disorders

Uncommon: Hiccups

 

  • Gastrointestinal disorders

Common: constipation

 

  • Hepatobiliary disorders

Uncommon: asymptomatic increases in liver function tests.

Paediatric population

The adverse event profiles in children and adolescents were comparable to that seen in adults.

 

OVERDOSE AND SPECIAL ANTIDOTE

SIGNS AND SYMPTOMS

There is limited experience of ondansetron overdose. In majority of cases, symptoms were similar to those already reported in patients receiving recommended doses. Manifestations of overdose that have been reported include visual disturbances, severe constipation, hypotension and a vasovagal episode with transient second-degree AV block.

 

TREATMENT

There is no specific antidote. In cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate. The use of ipecacuanha to treat overdose is not recommended.

 

STORAGE CONDITION

Store at temperatures not exceeding 30°C. Protect from light.

 

AVAILABILITY

10 film – coated tablet x 1 alu-alu blister packed in a carton along with a package insert.

 

Manufactured by

AMN Lifescience PVT. Ltd.

150 Sahajananand Estate, Sarkhej Tai City, Ahmedabad, Gujarat, India

Distributed by

The Cathay Drug Co., Inc.

2/F Vernida I Condominium 120 Amorsolo St. Legaspi Village, Makati City

Date of revision: December 2018

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