ondansetron (Rx)

>10%

Headache (9-27%)

Malaise/fatigue (9-13%)

Constipation (6-11%)

1-10%

Hypoxia (9%)

Drowsiness (8%)

Diarrhea (2-7%)

Dizziness (7%)

Fever (2-8%)

Gynecologic disorder (7%)

Anxiety (6%)

Urinary retention (5%)

Pruritus (2-5%)

Injection-site pain (4%)

Paresthesia (2%)

Cold sensation (2%)

Elevated liver function test results (1-5%)

<1%

Cardiac: 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/QTc interval prolongation have been reported

Gastrointestinal: Nausea and vomiting

Anaphylaxis

ECG alterations: Arrhythmias; prolongation of PR, QRS, and QT intervals

Hepatobiliary: Specific hepatic enzyme abnormalities, hepatic necrosis, and abnormal hepatic function

General: Flushing, rare cases of hypersensitivity reactions, sometimes severe (eg, anaphylactic reactions, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, stridor)

Local reactions: Pain, redness, and burning at injection site

Lower respiratory: Hiccups

Neurological: Oculogyric crisis, appearing alone, as well as with other dystonic reactions; transient dizziness during or shortly after intravenous infusion

Skin and subcutaneous tissue: Urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis

Eye Disorders: Transient blindness (predominantly during IV administration) reported to resolve within a few minutes up to 48 hr; transient blurred vision

Musculoskeletal and connective tissue: Arthralgia

Contraindications

Hypersensitivity

Coadministration with apomorphine; combination reported to cause profound hypotension and loss of consciousness

Cautions

Hypersensitivity reactions including anaphylaxis and bronchospasm may occur: discontinue therapy if suspected; monitor and treat promptly per standard of care until signs and symptoms resolve

Reduce dose with severe hepatic impairment

Use according to schedule, not PRN

Do not use instead of nasogastric suction

Ondansetron may mask progressive ileus or gastric distention in patients who are undergoing abdominal surgery or experiencing chemotherapy-induced nausea and vomiting; 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; should not be used instead of nasogastric suction

Serotonin syndrome reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs including SSRIs, SNRIs, MAO inhibitors, lithium, tramadol, methylene blue IV, and mirtazapine; if concomitant use with other serotonergic drugs is clinically warranted, patients should be made aware of potential increased risk for serotonin syndrome

Cross-sensitivity among selective serotonin antagonists may occur

Zofran ODT contains phenylalanine (caution for phenylketonurics)

Dose-dependent QT prolongation; avoid in patients with congenital long QT syndrome; ECG monitoring recommended in patients who have electrolyte abnormalities, CHF, or bradyarrhythmias or who are also receiving other medications that cause QT prolongation

Mechanism of Action

Mechanism not fully characterized; selective 5-HT3 receptor antagonist; binds to 5-HT3 receptors both in periphery and in CNS, with primary effects in GI tract

Has no effect on dopamine receptors and therefore does not cause extrapyramidal symptoms

Absorption

Bioavailability: 56-71% (PO); food increases extent of absorption (17%)

Onset: 30 min

Peak plasma time: IV, end of infusion; IM, 30 min; PO, 2 hr (tablet) or 1 hr (soluble film)

Distribution

Protein bound: 70-76%

Vd: Children, 1.7-3.7 L/kg; adults, 2.2-2.5 L/kg

Metabolism

Extensive hepatic metabolism, with hydroxylation followed by glucuronide (indole ring) or sulfate conjugation; metabolized by CYP2D6 and partly by CYP1A2 and CYP3A4

Metabolites: Glucuronide conjugate, sulfate conjugate (inactive)

Elimination

Half-life: 2-7 hr (children <15 years); 3-7 hr (adults); patients with mild to moderate hepatic impairment, 12 hr; patients with severe hepatic impairment (Child-Pugh class C), 20 hr

Renal Clearance: 0.26-0.38 L/hr/kg

Total body clearance: 600-700 mL/min

Excretion: Primarily urine (30-70%); feces (25%)

IV Incompatibilities

Syringe: Droperidol

Y-site: Acyclovir, allopurinol, aminophylline, amphotericin B, amphotericin B cholesteryl sulfate, ampicillin, ampicillin/sulbactam, amsacrine, cefepime, cefoperazone, 5-fluorouracil (5-FU; at 1 mg/mL ondansetron and 16 mg/mL 5-FU; may be compatible at 0.8 mg/mL 5-FU and up to 160 mcg/mL ondansetron), furosemide, ganciclovir, lorazepam, meropenem (at 50 mg/mL meropenem and 1 mg/mL ondansetron; may be compatible at 1 mg/mL each), methylprednisolone, piperacillin, sargramostim, sodium bicarbonate

IV Compatibilities

Solution: Compatible with most common solvents

Additive (partial list): Cisplatin, cyclophosphamide, cytarabine, decarbazine, dacarbazine with doxorubicin(?), doxorubicin, etoposide, hydromorphone, meropenem (incompatible at 20 g/L meropenem), methotrexate, morphine sulfate

Syringe: Alfentanil, atropine, dexamethasone (incompatible at 0.67 mg/mL dexamethasone and 1.07 mg/mL ondansetron), fentanyl, glycopyrrolate, meperidine, metoclopramide, midazolam, morphine sulfate, naloxone, neostigmine, propofol

Y-site (partial list): Alatrofloxacin, aldesleukin, azithromycin, bleomycin, carboplatin, cisplatin, cladribine, clindamycin, cyclophosphamide, cytarabine, dactinomycin, dopamine, heparin, hydromorphone, magnesium sulfate, meperidine, morphine sulfate, paclitaxel, potassium chloride, topotecan, vancomycin, vinblastine, vincristine, zidovudine

IV Preparation

No dilution necessary for premixed injection

Postoperative nausea and vomiting: No dilution necessary for 2 mg/mL vials

Chemotherapy-induced nausea and vomiting: Dilute IV injection (2 mg/mL vials, not premixed injection) in 50 mL D5W or NS

IV Administration

Infuse over 15 minutes after further dilution with 50 mL NS/D5W

Inject undiluted over at least 30 seconds, preferably over 2-5 minutes

IM Administration

No dilution necessary for premixed injection

Storage

Store at room temperature or refrigerate

Protect from light, excessive heat, and freezing