Ondansetron Amneal

Uses

Ondansetron Amneal is used for:

• Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy
• Prevention of nausea and vomiting associated with radiotherapy
• Prevention of post operative nausea and vomiting

Ondansetron Amneal is also used to associated treatment for these conditions: Chemotherapy-Induced Nausea and Vomiting (CINV), Cholestatic pruritus, Post Operative Nausea and Vomiting (PONV), Uremic Pruritus, Radiation therapy induced nausea and vomiting, Severe Hyperemesis gravidarum

How Ondansetron Amneal works

Ondansetron Amneal is a selective antagonist of the serotonin receptor subtype, 5-HT3 .

Cytotoxic chemotherapy and radiotherapy are associated with the release of serotonin (5-HT) from enterochromaffin cells of the small intestine, presumably initiating a vomiting reflex through stimulation of 5-HT3 receptors located on vagal afferents . Ondansetron Amneal may block the initiation of this reflex. Activation of vagal afferents may also cause a central release of serotonin from the chemoreceptor trigger zone of the area postrema, located on the floor of the fourth ventricle . Thus, the antiemetic effect of ondansetron is probably due to the selective antagonism of 5-HT3 receptors on neurons located in either the peripheral or central nervous systems, or both .

Although the mechanisms of action of ondansetron in treating postoperative nausea and vomiting and cytotoxic induced nausea and vomiting may share similar pathways, the role of ondansetron in opiate-induced emesis has not yet been formally established .

Dosage

Ondansetron Amneal dosage

Prevention of chemotherapy induced nausea & vomiting (CINV):

Adult-

• Tablet and oral solution: The recommended adult oral dosage of Ondansetron Amneal is 24 mg given as three 8 mg tablets in highly emetogenic chemotherapy. In case of moderately emetogenic chemotherapy the oral dose is one 8 mg Ondansetron Amneal tablet or 10 ml of Ondansetron Amneal oral solution given twice daily.
• Injection: The recommended i.v. dose of Ondansetron Amneal is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of Ondansetron Amneal.
• Suppository: The recommended adult dose is one 16 mg suppository 1-2 hours before treatment. Ondansetron Amneal should be continued for upto 5 days after a course of treatment.The recommended dose is one suppository daily.

Pediatric patients-

• Tablet and oral solution:for pediatric patients 4 through 11 years of age the dosage is one 4 mg Ondansetron Amneal tablet or 5ml of Ondansetron Amneal solution should be administered 3 times a day for 1 to 2 days after completion of chemotherapy.
• Injection: the dosage in pediatric patients 4 to 18 years of age should three 0.15-mg/kg doses.
• Suppository:Not recommended.

Radiotherapy induced nausea and vomiting:

Adult-

• Tablet and oral solution: the recommended oral dosage is one 8mg Ondansetron Amneal tablet or 10ml of Ondansetron Amneal oral solution given 3 times daily.

Post operative nausea & vomiting (PONV):

Adult-

• Tablet and oral solution: The recommended dosage is 16 mg given as two 8 mg Ondansetron Amneal tablets or 20 ml of Ondansetron Amneal oral solution 1hour before induction of anesthesia.
• Injection: The recommended I.V. dosage of Ondansetron Amneal for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, I.V. dose of Ondansetron Amneal 4 mg, administration of a second I.V. dose of 4 mg Ondansetron Amneal postoperatively does not provide additional control of nausea and vomiting.
• Suppository: The recommended adult dose is one 16 mg suppository 1-2 hours before treatment. Ondansetron Amneal should be continued for upto 5 days after a course of treatment.The recommended dose is one suppository daily.

Pediatric patients-

• Injection: The recommended I.V. dosage of Ondansetron Amneal for pediatric patients (2 to 12 years of age) isa single 0.1-mg/kg dose for pediatric patients weighing 40 kg or less, or a single 4 mg dose for pediatric patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes. Little information is available about dosage in pediatric patients younger than 2 years of age.
• Suppository: Not recommended.

Prior to IV infusion, dilute in 50 ml dextrose 5% inj or normal saline.

Side Effects

The most common adverse effects include headache, constipation, diarrhea. In chemotherapy induced nausea and vomiting rash has occurred in approximately 1% of patients receiving Ondansetron Amneal. Blurred vision, chest pain with or without ST segment depression, cardiac arrhythmias, hypotension and bradycardia have been rarely reported.

Toxicity

At present, there is little information concerning overdosage with ondansetron . Nevertheless, there have been certain cases of somewhat idiosyncratic adverse effects associated with particular dosages of ondansetron used .

“Sudden blindness” (amaurosis) of 2 to 3 minutes duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose . Hypotension (and faintness) occurred in another patient that took 48 mg of oral ondansetron . Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed . Neuromuscular abnormalities, autonomic instability, somnolence, and a brief generalized tonic-clonic seizure (which resolved after a dose of benzodiazepine) were observed in a 12-month-old infant who ingested seven or eight 8-mg ondansetron tablets (approximately forty times the recommended 0.1-0.15 mg/kg dose for a pediatric patient) . In all instances, however, the events resolved completely .

The safety of ondansetron for use in human pregnancy has not been established . Ondansetron Amneal is not teratogenic in animals . However, as animal studies are not always predictive of human response, the use of ondansetron in pregnancy is not recommended .

Ondansetron Amneal is excreted in the milk of lactating rats . It is not known if it is excreted in human milk, however, nursing is not recommended during treatment with ondansetron .

Insufficient information is available to provide dosage recommendations for children 3 years of age or younger .

Precaution

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

Interaction

In patients treated with potent inducers of CYP3A4 (i.e Phenytoin, Carbamazepine or Rifampicin), the oral clearance of Ondansetron Amneal was increased and Ondansetron Amneal blood concentrations were decreased. Data from small studies indicate that Ondansetron Amneal may reduce the analgesic effect of tramadol.

Food Interaction

• Take with or without food. The absorption is unaffected by food.

Ondansetron Amneal Drug Interaction

Major: duloxetineModerate: polyethylene glycol 3350, acetaminophen / hydrocodone, albuterolUnknown: amphetamine / dextroamphetamine, diphenhydramine, omega-3 polyunsaturated fatty acids, fluticasone nasal, pregabalin, metoprolol, metoprolol, acetaminophen, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol, alprazolam, cetirizine

Ondansetron Amneal Disease Interaction

Major: QT interval prolongationModerate: liver disease

Volume of Distribution

The volume of distribution of ondansetron has been recorded as being approximately 160L .

Elimination Route

Ondansetron Amneal is absorbed from the gastrointestinal tract and undergoes some limited first-pass metabolism . Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, was recorded as being approximately 56% to 60% . Bioavailability is also slightly enhanced by the presence of food .

Ondansetron Amneal systemic exposure does not increase proportionately to dose . The AUC from a 16-mg tablet was 24% greater than predicted from an 8-mg tablet dose . This may reflect some reduction of first-pass metabolism at higher oral doses .

Half Life

The half-life of ondansetron after either an 8 mg oral dose or intravenous dose was approximately 3-4 hours and could be extended to 6-8 hours in the elderly .

Clearance

The clearance values determined for ondansetron in various patient age groups were recorded as approximately 0.38 L/h/kg in normal adult volunteers aged 19-40 yrs, 0.32 L/h/kg in normal adult volunteers aged 61-74 yrs, 0.26 L/h/kg in normal adult volunteers aged >=75 yrs .

Elimination Route

Following oral or IV administration, ondansetron is extensively metabolised and excreted in the urine and faeces .

Pregnancy & Breastfeeding use

In pregnancy: Pregnancy category B. Reproduction studies at daily oral dose up to 10 and 30 mg/kg/day have been performed in animals and have revealed no evidence of impaired fertility harm to the fetus due to Ondansetron Amneal. There are, however, no adequate and well-controlled studies in pregnant women. So the drug should be used in pregnancy only if clearly needed.

In lactation: Ondansetron Amneal excretes in milk of lactating animals. Caution should be exercised when Ondansetron Amneal is administered to nursing mother.

Contraindication

Ondansetron Amneal is contraindicated in patients with known hypersensitivity to the drug.

Special Warning

Pediatric use: Can be given in children 1 month of age and above.

Geriatric use: No dosage adjustment is necessary in the elderly.Dosage adjustment for patients with impaired hepatic function:

• Tablet and Oral Solution: The total daily dose of 8 mg should not be exceeded.
• Injection: A single maximal dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended.
• Suppository: Not recommended

Acute Overdose

There is no specific antidote for Ondansetron Amneal overdose. In addition to the adverse events, hypotension (and faintness) occurred in a patient that took 48 mg of AVONA tablets. In all instances, the events resolved completely.

Storage Condition

Store in a cool and dry place, protected from light and moisture. For suppository- Store below 25º c.

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