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Introduction

  1. Pharmacology. Ondansetron is a selective serotonin (5-HT3) receptor antagonist with antiemetic activity due to its actions on serotonin receptors located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone. The mean peak plasma level occurred at 10 minutes after a 4-mg IV injection and 2 hours after an oral 8-mg dose given to normal adult volunteers. The drug is metabolized extensively in the liver primarily via hydroxylation, followed by glucuronide or sulfate conjugation. Ondansetron is a substrate for human hepatic cytochrome P-450 enzymes, mainly CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Elimination half-life in adults and children is 3-6 hours.
  2. Indications
    1. FDA-approved for the prevention of nausea and vomiting associated with chemotherapy, radiation therapy, and in the postoperative period.
    2. Off-label uses of ondansetron include prophylaxis and treatment of nausea and vomiting associated with xenobiotics, gastroenteritis, and hyperemesis gravidarum. 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.
  3. Contraindications
    1. Hypersensitivity to ondansetron or any component of the formulation. Anaphylaxis and bronchospasm have been reported. Cross-reactivity is possible, therefore use caution in patients with known hypersensitivity to other 5-HT3 receptor antagonists.
    2. The concomitant use of apomorphine with ondansetron is contraindicated on the basis of reports of profound hypotension and loss of consciousness.
    3. Ondansetron is associated with dose-dependent QT interval prolongation increasing the risk of torsade de pointes. Single doses >16 mg ondansetron IV are no longer recommended due to potential risk of QT prolongation.
    4. ECG monitoring is recommended in patients with electrolyte abnormalities, (eg, hypokalemia or hypomagnesemia), congestive heart failure, or bradycardia.
    5. Avoid in patients with congenital long QT syndrome.
    6. The orally disintegrating tablets (ODT) contain phenylalanine (a component of aspartame); use with caution in patients with phenylketonuria.
    7. Ondansetron is metabolized by hepatic cytochrome P-450 enzymes CYP3A4, CYP2D6, and CYP1A2, and inducers or inhibitors of these enzymes may change the clearance and half-life of ondansetron.
  4. Adverse effects
    1. Rare cases of immediate hypersensitivity reactions including anaphylactic reactions, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, and laryngeal edema have been reported. Also, delayed hypersensitivity reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported.
    2. Dose-dependent QT interval prolongation and dysrhythmias. Postmarketing cardiovascular events reported have included: torsade de pointes, ventricular and supraventricular tachycardia, PVCs, atrial fibrillation, bradycardia, second-degree heart block, and QT/QTc interval prolongation. Risk factors included IV administration of ondansetron, concomitant use of another QT interval prolonging medication, and preexisting cardiac disease or disorders associated with electrolyte abnormalities (eg, hypokalemia, hypomagnesemia).
    3. Anxiety, headache, drowsiness, fatigue, fever, dizziness, paresthesias, and migraine headaches. Rare cases of grand mal seizure.
    4. Rare reports consistent with, but not diagnostic of, extrapyramidal reactions. Oculogyric crisis, appearing either alone or with other dystonic reactions.
    5. Hepatic necrosis and increased liver enzymes associated with IV administration and concomitant hepatotoxic medications. Do not exceed a total daily dose of 8 mg in patients with severe liver disease.
    6. Diarrhea, constipation, and xerostomia.
    7. Injection site reactions (pain, redness), pruritus, and rash.
    8. Cases of transient blindness, predominantly during IV administration, have been reported.
    9. Use in pregnancy. FDA Category B (Introduction). Ondansetron is typically reserved for use when other antiemetics have failed.
  5. Drug or laboratory interactions
    1. Numerous IV incompatibilities, including aminophylline, sodium bicarbonate, furosemide, lorazepam, dexamethasone, methylprednisolone, sodium succinate, and thiopental. Ondansetron should not be mixed with alkaline solutions because a precipitate may form.
    2. Case reports suggest that 5-HT3 receptor antagonists might contribute to serotonin syndrome when used concurrently with other serotonergic drugs such as SSRIs, SNRIs, mirtazapine, fentanyl, MAOIs, tramadol, lithium, and methylene blue. However, this has been disputed.
  6. Dosage and method of administration
    1. Antiemetic for chemotherapy- and radiotherapy-induced nausea and vomiting. Ondansetron is most effective for prophylaxis when given at least 30 minutes before its antiemetic properties are needed (eg, prior to administration of chemotherapy).
      1. Adults: Give 0.15 mg/kg IV (maximum single dose of 16 mg due to potential of QT prolongation) in 50 mL of normal saline or 5% dextrose infused over 15 minutes. This may be repeated twice at 4-hour intervals.
      2. Pediatric patients (6 months through 12 years): Give 0.15 mg/kg (maximum dose of 16 mg) IV over 15 minutes. This may be repeated twice at 4-hour intervals for a total of 3 doses.
    2. Antiemetic for postoperative-induced nausea and vomiting.
      1. Adults. Give 4 mg IV over at least 30 seconds but preferably over 2-5 minutes. It may also be administered by IM route as a single injection.
      2. Pediatric patients (1 month through 12 years): Give 0.1 mg/kg/dose IV (undiluted) for patients 40 kg or less. Give 4 mg IV (undiluted) for patients greater than 40 kg. Administer IV dose over at least 30 seconds and preferably over 2-5 minutes.