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  1. Pharmacology. Ondansetron is a selective serotonin (5-HT3) receptor antagonist with powerful antiemetic activity, both centrally at the chemoreceptor trigger zone and peripherally at vagal nerve terminals. The onset is about 30 minutes after an intravenous dose and 60–90 minutes after an oral dose. The drug is metabolized extensively in the liver. The elimination half-life is 3–5.5 hours, increasing to as long as 20 hours in patients with severe liver disease.

  2. Indications

    1. FDA-approved for prophylaxis of highly or moderately emetogenic chemotherapy, prophylaxis of postoperative nausea and vomiting, and prophylaxis of radiation-induced nausea and vomiting.

    2. Ondansetron is used to treat intractable nausea and vomiting, particularly when the ability to administer activated charcoal or antidotal therapy (eg, N-acetylcysteine) is compromised. Not an FDA-approved indication.

  3. Contraindications

    1. Hypersensitivity to ondansetron or any component of the formulation. Hypersensitivity reactions have been reported in patients who have experienced hypersensitivity to other selective 5-HT3 receptor antagonists.

    2. The concomitant use of apomorphine with ondansetron is contraindicated based on reports of profound hypotension and loss of consciousness.

    3. Concurrent use of ondansetron and thioridazine, pimozide, or mesoridazine may result in an increase risk for cardiotoxicity (QT prolongation, torsade de pointes).

    4. Patients with phenylketonuria should be informed that Zofran ODT Orally Disintegrating Tablets contain phenylalanine (a component of aspartame). Use with caution in patients with phenylketonuria.

  4. Adverse effects

    1. Bronchospasm, hypersensitivity, anaphylaxis, and anaphylactoid reactions.

    2. Transient ECG changes, including QT-interval prolongation with potential for torsade de pointes, tachycardia, bradycardia, and angina.

    3. Anxiety, headache, drowsiness, fatigue, fever, and dizziness.

    4. Rare reports consistent with, but not diagnostic of, extrapyramidal reactions.

    5. Oculogyric crisis, appearing either alone or with other dystonic reactions.

    6. Diarrhea and constipation.

    7. Rare cases of grand mal seizure.

    8. Cases of transient blindness, predominantly during intravenous administration, have been reported.

    9. Use in pregnancy. FDA Category B. Not likely to cause harm when used as short-term therapy (See Introduction in Section III).

  5. Drug or laboratory interactions

    1. Ondansetron and the other selective 5-HT3 antagonists have been associated with dose-dependent ECG changes, including increases in PR, QRS, and QT intervals. Generally, these are not clinically relevant. However, when the drug is used with other agents that prolong these intervals, arrhythmia can occur.

    2. Numerous IV incompatibilities, including aminophylline, sodium bicarbonate, furosemide, lorazepam, dexamethasone, methylprednisolone, sodium succinate, and thiopental. Zofran should not be mixed with alkaline solutions because a precipitate may form.

    3. Apomorphine: reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron.

  6. Dosage and method of administration. Adults: Give 8 mg or 0.15 mg/kg IV in 50 mL of normal saline or 5% dextrose infused over 15 minutes. This may be repeated twice at 4-hour intervals. Alternative high-dose therapy: Give 32 mg in 50 mL of saline or dextrose administered over 15 minutes. (Do not repeat this dose.) Children (6 months–18 years): Give 0.15 mg/kg IV over 15 minutes. This may be repeated twice at 4-hour intervals.

    1. Ondansetron is most effective when given at least 30 minutes before its antiemetic properties are needed.

    2. Do not exceed a ...

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