ONDANSETRON HYDROCHLORIDE- ondansetron hydrochloride solution
Precision Dose Inc.
Ondansetron is 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 is also indicated for the prevention of postoperative nausea and/or vomiting.
The recommended dosage regimens for adult and pediatric patients are described in Table 1 and Table 2, respectively.
Corresponding doses of ondansetron tablets, orally disintegrating tablets and oral solution may be used interchangeably.
|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.|
|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.|
Ondansetron oral solution USP, 4mg/5mL, is a clear, colorless solution.
Ondansetron is 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.
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)].
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)].
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)].
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.
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. 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.
|Adverse Reaction||Ondansetron 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 US 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.
|Adverse Reaction||Ondansetron 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 dissolving tablets with water (24%) as compared with 2 subjects administered ondansetron orally dissolving tablets without water (8%).
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