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Pronunciation
(on DAN se tron)
Generic Available (U.S.)
Yes: Excludes oral soluble film
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Prevention of nausea and vomiting associated with moderately- to highly-emetogenic cancer chemotherapy; radiotherapy; prevention of postoperative nausea and vomiting (PONV); treatment of PONV if no prophylactic dose of ondansetron received
Use: Unlabeled/Investigational
Hyperemesis gravidarum; breakthrough treatment of nausea and vomiting associated with chemotherapy
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies; however, there are no adequate and well-controlled studies in pregnant women. Use of ondansetron for the treatment of nausea and vomiting of pregnancy (NVP) has been evaluated. Additional studies are needed to determine safety to the fetus, particularly during the first trimester. Based on preliminary data, use is generally reserved for severe NVP (hyperemesis gravidarum) or when conventional treatments are not effective.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to ondansetron, other selective 5-HT3 antagonists, or any component of the formulation; concomitant use of apomorphine
Warnings/Precautions
Concerns related to adverse effects:
• Allergic reactions: Use with caution in patients allergic to other 5-HT3 receptor antagonists; cross-reactivity has been reported.
• ECG effects: Selective 5-HT3 antagonists, including ondansetron, have been associated with a number of dose-dependent increases in ECG intervals (eg, PR, QRS duration, QT/QTc, JT), usually occurring 1-2 hours after I.V. administration. In general, these changes are not clinically relevant, however, when used in conjunction with other agents that prolong these intervals, arrhythmia may occur. When used with agents that prolong the QT interval (eg, Class I and III antiarrhythmics), clinically relevant QT interval prolongation may occur resulting in torsade de pointes. A number of trials have shown that 5-HT3 antagonists produce QT interval prolongation to variable degrees. Use with caution in patients at risk of QT prolongation and/or ventricular arrhythmia. Reduction in heart rate may also occur with the 5-HT3 antagonists. I.V. formulations of 5-HT3 antagonists have more association with ECG interval changes, compared to oral formulations.
Disease-related concerns:
• Hepatic impairment: Dose recommendations provided for patients with severe hepatic impairment (Child-Pugh class C); use with caution in mild-moderate hepatic impairment; clearance is decreased and half-life increased in hepatic impairment.
• Long QT syndrome: Use with caution in patients with congenital long QT syndrome or other risk factors for QT prolongation (eg, medications known to prolong QT interval, electrolyte abnormalities [hypokalemia or hypomagnesemia], and cumulative high-dose anthracycline therapy).
Dosage form specific issues:
• Phenylalanine: Orally-disintegrating tablets contain phenylalanine.
Other warnings/precautions:
• Chemotherapy-related emesis: For chemotherapy, should be used on a scheduled basis, not on an “as needed” (PRN) basis, since data support the use of this drug only in the prevention of nausea and vomiting (due to antineoplastic therapy) and not in the rescue of nausea and vomiting. Should only be used in the first 24-48 hours of chemotherapy. Data does not support any increased efficacy in delayed nausea and vomiting.
• Ileus or gastric distention: Does not stimulate gastric or intestinal peristalsis; may mask progressive ileus and/or gastric distension.
Adverse Reactions
Note: Percentages reported in adult patients.
>10%:
Central nervous system: Headache (9% to 27%), malaise/fatigue (9% to 13%)
Gastrointestinal: Constipation (6% to 11%)
1% to 10%:
Central nervous system: Drowsiness (8%), fever (2% to 8%), dizziness (4% to 7%), anxiety (6%), cold sensation (2%)
Dermatologic: Pruritus (2% to 5%), rash (1%)
Gastrointestinal: Diarrhea (2% to 7%)
Genitourinary: Gynecological disorder (7%), urinary retention (5%)
Hepatic: ALT increased (1% to 5%), AST increased (1% to 5%)
Local: Injection site reaction (4%; pain, redness, burning)
Neuromuscular & skeletal: Paresthesia (2%)
Respiratory: Hypoxia (9%)
<1%: Anaphylaxis, angina, bronchospasm, ECG changes, extrapyramidal symptoms, grand mal seizure, hypokalemia, hypotension, tachycardia, vascular occlusive events
Postmarketing and/or case reports: Abnormal hepatic function, anaphylactoid reactions, angioedema, arrhythmia, arthralgia, atrial fibrillation, AV block, blindness (transient/following infusion; lasting ≤48 hours), blurred vision (transient/following infusion), bradycardia, cardiopulmonary arrest, chest discomfort, chills, dyspnea, dystonic reaction, electrocardiographic alterations (second-degree heart block and ST-segment depression), flushing, hepatic failure, hepatic necrosis, hepatitis, hiccups, hyperhidrosis, hypersensitivity reaction, jaundice, laryngeal edema, laryngospasm, lethargy, oculogyric crisis, palpitation, premature ventricular contractions (PVC), QT interval increased, shock, shortness of breath, stridor, supraventricular tachycardia, syncope, torsade de pointes, urticaria, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (major), P-glycoprotein; Inhibits CYP1A2 (weak), 2C9 (weak), 2D6 (weak)
Drug Interactions
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Tablet: Food slightly increases the extent of absorption.
Herb/Nutraceutical: St John's wort may decrease ondansetron levels.
Storage
Oral soluble film: Store between 20°C and 25°C (68°F and 77°F). Store pouches in cartons; keep film in individual pouch until ready to use.
Oral solution: Store between 15°C and 30°C (59°F and 86°F). Protect from light.
Premixed bag: Store between 2°C and 30°C (36°F and 86°F). Protect from light.
Tablet: Store between 2°C and 30°C (36°F and 86°F).
Vial: Store between 2°C and 30°C (36°F and 86°F). Protect from light. Stable when mixed in D5W or NS for 48 hours at room temperature.
Reconstitution
Prior to I.V. infusion, dilute in 50 mL D5W or NS.
Compatibility
Stable in D51/2NS, D5NS, D5W, mannitol 10%, LR, NS, sodium chloride 3%; do not mix injection with alkaline solutions.
Y-site administration: Compatible: Alatrofloxacin, aldesleukin, amifostine, amikacin, aztreonam, bleomycin, carboplatin, carmustine, cefazolin, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, cefuroxime, chlorpromazine, cimetidine, cisatracurium, cisplatin, cladribine, clindamycin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, dexamethasone sodium phosphate, diphenhydramine, docetaxel, dopamine, doxorubicin, doxorubicin liposome, doxycycline, droperidol, etoposide, etoposide phosphate, famotidine, filgrastim, floxuridine, fluconazole, fludarabine, gatifloxacin, gemcitabine, gentamicin, haloperidol, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, ifosfamide, imipenem/cilastatin, linezolid, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, mesna, methotrexate, metoclopramide, mitomycin, mitoxantrone, morphine, paclitaxel, paclitaxel with ranitidine, pentostatin, piperacillin/tazobactam, potassium chloride, prochlorperazine edisylate, promethazine, ranitidine, remifentanil, sodium acetate, streptozocin, teniposide, thiotepa, ticarcillin, ticarcillin/clavulanate, topotecan, vancomycin, vinblastine, vincristine, vinorelbine, zidovudine. Incompatible: Acyclovir, allopurinol, aminophylline, amphotericin B, amphotericin B cholesteryl sulfate complex, ampicillin, ampicillin/sulbactam, amsacrine, cefepime, cefoperazone, furosemide, ganciclovir, lorazepam, methylprednisolone sodium succinate, piperacillin, sargramostim, sodium bicarbonate. Variable (consult detailed reference): Fluorouracil, meropenem.
Mechanism of Action
Selective 5-HT3-receptor antagonist, blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone
Pharmacodynamics/Kinetics
Onset of action: ~30 minutes
Absorption: Oral: Well absorbed from GI tract
Distribution: Vd: Children: 1.7-3.7 L/kg; Adults: 2.2-2.5 L/kg
Protein binding, plasma: 70% to 76%
Metabolism: Extensively hepatic via hydroxylation, followed by glucuronide or sulfate conjugation; CYP1A2, CYP2D6, and CYP3A4 substrate; some demethylation occurs
Bioavailability: Oral: 56% to 71% (some first pass metabolism); Rectal: 58% to 74%
Half-life elimination: Children <15 years: 2-7 hours; Adults: 3-6 hours
Mild-to-moderate hepatic impairment (Child-Pugh classes A and B): Adults: 12 hours
Severe hepatic impairment (Child-Pugh class C): Adults: 20 hours
Time to peak: Oral: ~2 hours; Oral soluble film: ~1 hour
Excretion: Urine (44% to 60% as metabolites, ~5% as unchanged drug); feces (~25%)
Dosage
Children:
I.V.: Note: Premixed injection not for use in children.
Prevention of chemotherapy-induced emesis: 6 months to 18 years: 0.15 mg/kg/dose administered 30 minutes prior to chemotherapy, 4 and 8 hours after the first dose or 0.45 mg/kg/day as a single dose
Prevention of postoperative nausea and vomiting: 1 month to 12 years:
≤40 kg: 0.1 mg/kg as a single dose
>40 kg: 4 mg as a single dose
Oral: Prevention of moderately-emetogenic chemotherapy-induced emesis:
4-11 years: 4 mg 30 minutes before chemotherapy; repeat 4 and 8 hours after initial dose, then 4 mg every 8 hours for 1-2 days after chemotherapy completed
≥12 years: Refer to adult dosing.
Adults:
I.V.:
Prevention of chemotherapy-induced emesis:
0.15 mg/kg 3 times/day beginning 30 minutes prior to chemotherapy or
0.45 mg/kg once daily or
8-10 mg 1-2 times/day or
24 mg or 32 mg once daily
Treatment of hyperemesis gravidum (unlabeled use): 8 mg administered over 15 minutes every 12 hours or 1 mg/hour infused continuously for up to 24 hours
I.M., I.V.: Postoperative nausea and vomiting (PONV): 4 mg as a single dose approximately 30 minutes before the end of anesthesia (see Note below) or as treatment if vomiting occurs after surgery (Gan, 2007).
Note: The manufacturer recommends administration immediately before induction of anesthesia; however, this has been shown not to be as effective as administration at the end of surgery (Sun, 1997). Repeat doses given in response to inadequate control of nausea/vomiting from preoperative doses are generally ineffective.
Oral:
Chemotherapy-induced emesis prophylaxis:
Highly-emetogenic agents/single-day therapy: 24 mg given 30 minutes prior to the start of therapy
Moderately-emetogenic agents: 8 mg beginning 30 minutes before chemotherapy; repeat dose 8 hours after initial dose, then 8 mg every 12 hours for 1-2 days after chemotherapy completed
Radiation-induced nausea and vomiting prophylaxis:
Total body irradiation: 8 mg 1-2 hours before daily each fraction of radiotherapy
Single high-dose fraction radiotherapy to abdomen: 8 mg 1-2 hours before irradiation, then 8 mg every 8 hours after first dose for 1-2 days after completion of radiotherapy
Daily fractionated radiotherapy to abdomen: 8 mg 1-2 hours before irradiation, then 8 mg 8 hours after first dose for each day of radiotherapy
Postoperative nausea and vomiting: 16 mg given 1 hour prior to induction of anesthesia
Treatment of hyperemesis gravidum (unlabeled use): 8 mg every 12 hours
Elderly: No dosing adjustment required
Dosage adjustment in renal impairment: No dosing adjustment required
Dosage adjustment in hepatic impairment: Severe liver disease (Child-Pugh C): Maximum daily dose: 8 mg
Administration: Oral
Oral dosage forms should be given 30 minutes prior to chemotherapy; 1-2 hours before radiotherapy; 1 hour prior to the induction of anesthesia.
Orally-disintegrating tablets: Do not remove from blister until needed. Peel backing off the blister, do not push tablet through. Using dry hands, place tablet on tongue and allow to dissolve. Swallow with saliva.
Oral soluble film: Do not remove from pouch until immediately before use. Using dry hands, place film on top of tongue and allow to dissolve (4-20 seconds). Swallow with or without liquid. If using more than one film, each film should be allowed to dissolve completely before administering the next film.
Administration: I.M.
Should be given undiluted.
Administration: I.V.
IVPB: Dilute in 50 mL D5W or NS. Infuse over 15-30 minutes; 24-hour continuous infusions have been reported, but are rarely used.
Chemotherapy-induced nausea and vomiting: Give first dose 30 minutes prior to beginning chemotherapy.
I.V. push: Prevention of postoperative nausea and vomiting: Single doses may be administered I.V. injection over 2-5 minutes as undiluted solution.
Administration: I.V. Detail
pH: 3-4
Monitoring Parameters
Closely monitor patients <4 months of age
Dietary Considerations
Take without regard to meals. Some products may contain phenylalanine.
Patient Education
This drug is given to prevent nausea and vomiting. If this medication is given by intravenous infusion you will be monitored during infusion. Report immediately any chest pain, respiratory difficulty, or pain or itching at infusion site. May cause headache, drowsiness, or dizziness. Report chest pain or palpitations, persistent headache, excessive drowsiness, fever, constipation, or diarrhea.
Orally-disintegrating tablets: Using dry hands, place tablet on tongue and allow to dissolve. Swallow with saliva.
Geriatric Considerations
Elderly have a slightly decreased hepatic clearance rate. This does not, however, require a dose adjustment.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
Ondansetron is a safer alternative than phenothiazines (ie, promethazine) for the treatment of moderate-to-severe postoperative nausea and vomiting. The cost can be a limitation.
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
Barbiturates and carbamazepine may increase the metabolism of ondansetron; monitor for diminished effects
Nursing: Physical Assessment/Monitoring
Assess allergy history (selective 5-HT3 receptor antagonists) prior to administering. Use with caution in presence of, or potential for, cardiac conduction abnormalities (eg, QT prolongation, medication known to prolong QT interval, electrolyte abnormalities). Oral and I.V. doses have different schedules and should not be administered on "PRN" basis.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Film, soluble, oral:
Zuplenz®: 4 mg (10s); 8 mg (10s) [peppermint flavor]
Infusion, premixed in D5W [preservative free]: 32 mg (50 mL)
Infusion, premixed in NS [preservative free]: 32 mg (50 mL)
Injection, solution: 2 mg/mL (2 mL, 20 mL)
Zofran®: 2 mg/mL (2 mL [DSC], 20 mL)
Injection, solution [preservative free]: 2 mg/mL (2 mL)
Solution, oral: 4 mg/5 mL (5 mL, 50 mL)
Zofran®: 4 mg/5 mL (50 mL) [contains sodium benzoate; strawberry flavor]
Tablet, oral: 4 mg, 8 mg, 24 mg [DSC]
Zofran®: 4 mg, 8 mg
Tablet, orally disintegrating, oral: 4 mg, 8 mg
Zofran® ODT: 4 mg, 8 mg [contains phenylalanine <0.03 mg/tablet; strawberry flavor]
Pricing: U.S. (www.drugstore.com)
Tablet, orally-disintegrating (Ondansetron)
8 mg (30): $40.99
Tablet, orally-disintegrating (Zofran ODT)
4 mg (30): $659.95
Tablets (Ondansetron HCl)
4 mg (30): $66.99
Tablets (Zofran)
4 mg (10): $245.00
8 mg (30): $1169.91
Extemporaneously Prepared
Note: Commercial oral solution is available (0.8 mg/mL)
If commercial oral solution is unavailable, a 0.8 mg/mL syrup may be made with ondansetron tablets, Ora-Plus® (Paddock), and any of the the following syrups: Cherry syrup USP, Syrpalta® (HUMCO), Ora-Sweet® (Paddock), or Ora-Sweet® Sugar-Free (Paddock). Crush ten 8 mg tablets in a mortar and reduce to a fine powder (flaking of the tablet coating occurs). Add 50 mL Ora-Plus® in 5 mL increments, mixing thoroughly; mix while adding the chosen syrup in incremental proportions to almost 100 mL; transfer to a calibrated bottle, rinse mortar with syrup, and add sufficient quantity of syrup to make 100 mL. Label "shake well" and "refrigerate". Stable for 42 days refrigerated (Trissel, 1996).
Rectal suppositories: Calibrate a suppository mold for the base being used. Determine the displacement factor (DF) for ondansetron for the base being used (Fattibase® = 1.1; Polybase® = 0.6). Weigh the ondansetron tablet(s). Divide the tablet weight by the DF; this result is the weight of base displaced by the drug. Subtract the weight of base displaced from the calculated weight of base required for each suppository. Grind the ondansetron tablets in a mortar and reduce to a fine powder. Weigh out the appropriate weight of suppository base. Melt the base over a water bath (<55°C). Add the ondansetron powder to the suppository base and mix well. Pour the mixture into the suppository mold and cool. Stable for at least 30 days refrigerated (Tenjarla, 1998).
Tenjarla SN, Ward ES, and Fox JL, "Ondansetron Suppositories: Extemporaneous Preparation, Drug Release, Stability and Flux Through Rabbit Rectal Membrane," Int J Pharm Compound, 1998, 2(1):83-8.
Trissel LA, Trissel's Stability of Compounded Formulations, Washington, DC: American Pharmaceutical Association, 1996.
References
American College of Obstetrics and Gynecology, ACOG (American College of Obstetrics and Gynecology) Practice Bulletin: “Nausea and Vomiting of Pregnancy,” Obstet Gynecol, 2004, 103(4):803-14.
Chaffee BJ and Tankanow RM, “Ondansetron - the First of a New Class of Antiemetic Agents,” Clin Pharm, 1991, 10(6):430-6.
Gan TJ, Meyer TA, Apfel CC, et al, "Society for Ambulatory Anesthesia Guidelines for the Management of Postoperative Nausea and Vomiting," Anesth Analg, 2007, 105(6):1615-28.
Kris MG, Hesketh PJ, Somerfield MR, et al, “American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006,” J Clin Oncol, 2006, 24(18):2932-47.
Levichek Z, Atanackovic G, Oepkes D, et al, “Nausea and Vomiting of Pregnancy. Evidence-Based Treatment Algorithm,” Can Fam Physician, 2002, 48:267-8, 277.
Multinational Association of Supportive Care in Cancer (MASCC), “Antiemetic Guidelines,” Updated April 2010. Available at http://data.memberclicks.com/site/mascc/MASCC_Guidelines_English_2010.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Antiemesis,” Version 2.2010. Available at http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf
Navari RM and Koeller JM, “Electrocardiographic and Cardiovascular Effects of the 5-Hydroxytryptamine3 Receptor Antagonists,” Ann Pharmacother, 2003, 37(9):1276-86.
Roila F and Del Favero A, “Ondansetron Clinical Pharmacokinetics,” Clin Pharmacokinet, 1995, 29(2):95-109.
Siu SS, Yip SK, Cheung CW, et al, “Treatment of Intractable Hyperemesis Gravidarum by Ondansetron,” Eur J Obstet Gynecol Reprod Biol, 2002, 105(1):73-4.
Sun R, Klein KW, and White PF, "The Effect of Timing of Ondansetron Administration in Outpatients Undergoing Otolaryngologic Surgery," Anesth Analg, 1997, 84(2):331-6.
Tramer MR, Moore RA, Reynolds DJ, et al, “A Quantitative Systematic Review of Ondansetron in Treatment of Established Postoperative Nausea and Vomiting,” BMJ, 1997, 314(7087):1088-92.
Wilde MI and Markham A, “Ondansetron. A Review of Its Pharmacology and Preliminary Clinical Findings in Novel Application,” Drugs, 1996, 52(5):773-94.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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