Ondansetron

ONDANSETRON — ondansetron tablet, orally disintegrating
RPK Pharmaceuticals, Inc.

1 INDICATIONS AND USAGE

Ondansetron orally disintegrating tablets are indicated for the prevention of nausea and vomiting associated with:

• highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m²
• initial and repeat courses of moderately emetogenic cancer chemotherapy
• radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen

Ondansetron orally disintegrating tablets also indicated for the prevention of postoperative nausea and/or vomiting.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

The recommended dosage regimens for adult and pediatric patients are described in Table 1 and Table 2, respectively. Corresponding doses of ondansetron tablets, ondansetron orally disintegrating tablets and ondansetron oral solution may be used interchangeably.

Table 1: Adult Recommended Dosage Regimen for Prevention of Nausea and Vomiting

Indication	Dosage Regimen
Highly Emetogenic Cancer Chemotherapy	A single 24 mg dose administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin greater than or equal to 50 mg/m2
Moderately Emetogenic Cancer Chemotherapy	8 mg administered 30 minutes before the start of chemotherapy, with a subsequent 8 mg dose 8 hours after the first dose.Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.
Radiotherapy	For total body irradiation: 8 mg administered 1 to 2 hours before each fraction of radiotherapy each day.For single high-dose fraction radiotherapy to the abdomen: 8 mg administered 1 to 2 hours before radiotherapy, with subsequent 8 mg doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.For daily fractionated radiotherapy to the abdomen: 8 mg administered 1 to 2 hours before radiotherapy, with subsequent 8 mg doses every 8 hours after the first dose for each day radiotherapy is given.
Postoperative	16 mg administered 1 hour before induction of anesthesia.

Table 2: Pediatric Recommended Dosage Regimen for Prevention of Nausea and Vomiting

Indication

Dosage Regimen

Moderately Emetogenic Cancer Chemotherapy

12 to 17 years of age: 8 mg administered 30 minutes before the start of chemotherapy, with a subsequent 8 mg dose 8 hours after the first dose. Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.4 to 11 years of age: 4 mg administered 30 minutes before the start of chemotherapy, with a subsequent 4 mg dose 4 and 8 hours after the first dose. Then administer 4 mg three times a day for 1 to 2 days after completion of chemotherapy.

2.2 Dosage in Hepatic Impairment

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), do not exceed a total daily dose of 8 mg [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.3 Administration Instructions for Ondansetron Orally Disintegrating Tablets

Do not attempt to push ondansetron orally disintegrating tablets through the foil backing. With dry hands, remove the tablet from the bottle or PEEL BACK the foil backing of 1 blister and GENTLY remove the tablet. IMMEDIATELY place the ondansetron orally disintegrating tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva. Administration with liquid is not necessary.

3 DOSAGE FORMS AND STRENGTHS

Ondansetron Orally Disintegrating Tablets USP, 4 mg are white to off-white, round tablets debossed with ‘5’ on one side and ‘E’ on the other side with an embossed circular edge.

Ondansetron Orally Disintegrating Tablets USP, 8 mg are white to off-white, round tablets debossed with ‘7’ on one side and ‘E’ on the other side with an embossed circular edge.

4 CONTRAINDICATIONS

Ondansetron orally disintegrating tablets are contraindicated in patients:

• known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any of the components of the formulation [see Adverse Reactions (6.2)]
• receiving concomitant apomorphine due to the risk of profound hypotension and loss of consciousness

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT₃ receptor antagonists. If hypersensitivity reactions occur, discontinue use of ondansetron; treat promptly per standard of care and monitor until signs and symptoms resolve [see Contraindications (4)].

5.2 QT Prolongation

Electrocardiogram (ECG) changes including QT interval prolongation have been seen in patients receiving ondansetron. In addition, postmarketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking other medicinal products that lead to QT prolongation [see Clinical Pharmacology (12.2)].

5.3 Serotonin Syndrome

The development of serotonin syndrome has been reported with 5-HT₃ receptor antagonists alone. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of ondansetron alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT₃ receptor antagonist use occurred in a post-anesthesia care unit or an infusion center.
Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of ondansetron and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ondansetron and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if ondansetron is used concomitantly with other serotonergic drugs [see Drug Interactions (7.1), Overdosage (10)].

5.4 Masking of Progressive Ileus and Gastric Distension

The use of ondansetron in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension. Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction.
Ondansetron is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction.