FDA Label for Ondansetron Odt

Dosage And Administration Section

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.

Indications And Usage Section

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.

Adverse Reactions Section

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reactions have been reported in clinical trials of patients treated with ondansetron, the active ingredient of ondansetron orally disintegrating tablets. A causal relationship to therapy with ondansetron was unclear in many cases.

Prevention of Chemotherapy-Induced Nausea and Vomiting

The most common adverse reactions reported in greater than or equal to 4% of 300 adults receiving a single 24 mg dose of ondansetron orally in 2 trials for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy (cisplatin greater than or equal to 50 mg/m2) were: headache (11%) and diarrhea (4%).

The most common adverse reactions reported in 4 trials in adults for the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy (primarily cyclophosphamide-based regimens) are shown in Table 3.

Table 3: Most Common Adverse Reactions in Adultsa for the Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Chemotherapy [Primarily Cyclophosphamide-based Regimens]
a Reported in greater than or equal to 5% of patients treated with ondansetron orally disintegrating tablets and at a rate that exceeded placebo.
Adverse Reaction
Ondansetron Orally
Disintegrating Tablets
8 mg Twice Daily
(n = 242)
Placebo
(n = 262)
Headache
58 (24%)
34 (13%)
Malaise/fatigue
32 (13%)
6 (2%)
Constipation
22 (9%)
1 (<1%)
Diarrhea
15 (6%)
10 (4%)

Less Common Adverse Reactions

Central Nervous System: Extrapyramidal reactions (less than 1% of patients).

Hepatic: Aspartate transaminase (AST) and/or alanine transaminase (ALT) values exceeded twice the upper limit of normal in approximately 1% to 2% of 723 patients receiving ondansetron and cyclophosphamide-based chemotherapy in U.S. clinical trials. The increases were transient and did not appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur. The role of cancer chemotherapy in these biochemical changes is unclear.

Liver failure and death has been reported in cancer patients receiving concurrent medications, including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear.

Integumentary: Rash (approximately 1% of patients).

Other (less than 2%): Anaphylaxis, bronchospasm, tachycardia, angina, hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures. Except for bronchospasm and anaphylaxis, the relationship to ondansetron is unclear.

Prevention of Radiation-Induced Nausea and Vomiting

The most common adverse reactions (greater than or equal to 2%) reported in patients receiving ondansetron and concurrent radiotherapy were similar to those reported in patients receiving ondansetron and concurrent chemotherapy and were headache, constipation, and diarrhea.

Prevention of Postoperative Nausea and Vomiting

The most common adverse reactions reported in adults in trial(s) of prevention of postoperative nausea and vomiting are shown in Table 4. In these trial(s), patients were receiving multiple concomitant perioperative and postoperative medications in both treatment groups.

Table 4: Most Common Adverse Reactions in Adultsa for the Prevention of Postoperative Nausea and Vomiting
a Reported in greater than or equal to 5% of patients treated with ondansetron orally disintegrating tablets and at a rate that exceeded placebo.
Adverse Reaction
Ondansetron Orally
Disintegrating Tablets
16 mg as a Single Dose
(n = 550)
Placebo
(n = 531)
Headache
49 (9%)
27 (5%)
Hypoxia
49 (9%)
35 (7%)
Pyrexia
45 (8%)
34 (6%)
Dizziness
36 (7%)
34 (6%)
Gynecological disorder
36 (7%)
33 (6%)
Anxiety/agitation
33 (6%)
29 (5%)
Urinary retention
28 (5%)
18 (3%)
Pruritus
27 (5%)
20 (4%)

In a crossover study with 25 subjects, headache was reported in 6 subjects administered ondansetron orally disintegrating tablets with water (24%) as compared with 2 subjects administered ondansetron orally disintegrating tablets without water (8%).

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ondansetron. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular

Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular contractions, and atrial fibrillation), bradycardia, electrocardiographic alterations (including second-degree heart block, QT/QTc interval prolongation, and ST segment depression), palpitations, and syncope. Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.

General

Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylactic reactions, angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been reported.

Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients receiving injectable ondansetron.

Hepatobiliary

Liver enzyme abnormalities.

Lower Respiratory

Hiccups.

Neurology

Oculogyric crisis, appearing alone, as well as with other dystonic reactions.

Skin

Urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Eye Disorders

Cases of transient blindness, predominantly during intravenous administration, have been reported. These cases of transient blindness were reported to resolve within a few minutes up to 48 hours.