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Generic Name: Ondansetron Hydrochloride
Class: 5-HT3 Receptor Antagonists
VA Class: GA700
Chemical Name: 1,2,3,9-Tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one monohydrochloride dihydrate
Molecular Formula: C18H19N3O•ClH• 2H2O
CAS Number: 103639-04-9

Introduction

Antiemetic; selective inhibitor of type 3 serotonergic (5-HT3) receptors.1 33

Uses for Zofran

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention of nausea and vomiting associated with emetogenic cancer chemotherapy; may use orally with highly emetogenic chemotherapy (i.e., cisplatin ≥50 mg/m2) or initial and repeat courses of moderately emetogenic chemotherapy, or IV with initial and repeat courses of emetogenic chemotherapy, including high-dose cisplatin.1 3 6 8 10 27 28 29 30 31 33 36 37 38 39 40 41

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Postoperative Nausea and Vomiting

Prevention of postoperative nausea and vomiting.1 4 11 12 32 33 76

Routine prophylaxis not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.1 33

Recommended for patients who, in the clinician’s judgement, must avoid nausea and/or vomiting postoperatively, even when anticipated incidence is low.1 33

Radiation-induced Nausea and Vomiting

Prevention of nausea and vomiting associated with radiation, either total body irradiation or single high-dose fraction or daily fractionated radiation to the abdomen.33

Zofran Dosage and Administration

Administration

Administer orally, by IV infusion, or by IV or IM injection.1 33

Oral Administration

Administer orally as conventional tablet, orally disintegrating tablet, or oral solution.33

Commercially available oral solution and orally disintegrating tablets may be used interchangeably.33

Do not remove orally disintegrating tablet from blister until just prior to dosing; do not push through foil.33 With dry hands, peel open blister package, and gently remove the tablet; place tablet on tongue to dissolve, and swallow with saliva.33

Administration of orally disintegrating tablet with liquid is not necessary.33

IV Administration

For prevention of cancer chemotherapy-induced nausea/vomiting, administer by IV infusion using diluted injection.1

For prevention of postoperative nausea and vomiting, administer undiluted by IV injection.1

Dilution

For IV infusion, dilute ondansetron hydrochloride injection in 50 mL of 5% dextrose injection or 0.9% sodium chloride injection.1

For IV injection, no dilution required.1

Rate of Administration

IV infusion: Infuse over 15 minutes.1

IV injection: Inject over a period of ≥30 seconds, preferably over 2–5 minutes.1

IM Administration

For prevention of postoperative nausea and vomiting in adults, may administer undiluted by IM injection as an alternative to IV injection.1 (See Postoperative Nausea and Vomiting under Dosage and Administration.)

Dosage

Available as ondansetron hydrochloride dihydrate (for oral or IV use) and as ondansetron base (orally disintegrating tablets); dosage expressed in terms of ondansetron.1 33

Pediatric Patients

Cancer Chemotherapy-induced Nausea and Vomiting
Prevention
Oral

Children 4–11 years of age: Initially, 4 mg given 30 minutes before administration of moderately emetogenic chemotherapy, followed by subsequent 4-mg doses given 4 and 8 hours after first dose.33 Continue with 4 mg every 8 hours for 1–2 days after completion of chemotherapy.33

Children ≥12 years of age: Initially, 8 mg given 30 minutes before administration of moderately emetogenic chemotherapy, followed by a subsequent 8-mg dose given 8 hours after first dose.33 Continue with 8 mg every 12 hours for 1–2 days after completion of chemotherapy.33

IV

Pediatric patients 6 months to 18 years of age: 0.15 mg/kg (maximum 16 mg per dose) by IV infusion beginning 30 minutes before start of emetogenic chemotherapy, followed by subsequent 0.15-mg/kg doses given 4 and 8 hours after first dose.1

Postoperative Nausea and Vomiting
Prevention
IV

Infants and children 1 month to 12 years of age weighing ≤40 kg: 0.1 mg/kg as a single dose by IV injection immediately before or after induction of anesthesia.1

Children ≤12 years of age weighing >40 kg: 4 mg as a single dose by IV injection immediately before or after induction of anesthesia.1

Treatment
IV

Infants and children 1 month to 12 years of age weighing ≤40 kg: 0.1 mg/kg as a single dose by IV injection postoperatively, if nausea and/or vomiting occur shortly after surgery.1

Children ≤12 years of age weighing >40 kg: 4 mg as a single dose by IV injection postoperatively, if nausea and/or vomiting occur shortly after surgery.1

Efficacy of a second dose administered postoperatively after a single, prophylactic, preinduction IV dose has failed to achieve adequate control of postoperative nausea and vomiting has not been evaluated in children; such repeat doses are not effective in adults.1

Adults

Cancer Chemotherapy-induced Nausea and Vomiting
Prevention
Oral

Initially, 8 mg given 30 minutes before administration of moderately emetogenic chemotherapy, followed by a subsequent 8-mg dose given 8 hours after first dose.33 Continue with 8 mg every 12 hours for 1–2 days after completion of chemotherapy.33

24 mg as a single dose given 30 minutes before administration of single-day highly emetogenic chemotherapy.33

IV

0.15 mg/kg (maximum 16 mg per dose) by IV infusion beginning 30 minutes before administration of emetogenic chemotherapy, followed by 0.15 mg/kg infused 4 and 8 hours after first dose.1

Single IV dose of 32 mg no longer recommended (see Cardiac Effects under Cautions); efficacy and safety of alternative single-dose IV regimens for prevention of cancer chemotherapy-induced nausea and vomiting not established.78

Postoperative Nausea and Vomiting
Prevention
Oral

16 mg as a single dose given 1 hour before induction of anesthesia.33

IV

4 mg as a single dose by IV injection (undiluted) immediately before induction of anesthesia.1

Limited information available regarding dosage in patients weighing >80 kg.1

If adequate control of postoperative nausea and vomiting is not achieved after a single, prophylactic, preinduction IV dose, a second IV dose postoperatively does not provide additional control of nausea and vomiting.1

If nausea and/or vomiting occur shortly (within 2 hours) after surgery in a patient who did not receive prophylactic antiemetic therapy, 4 mg as a single dose by IV injection (undiluted) postoperatively.1

IM

4 mg as a single dose by IM injection (undiluted) as an alternative to IV administration.1

Limited information available regarding dosage in patients weighing >80 kg.1

Radiation-induced Nausea and Vomiting
Prevention, Usual Dosage
Oral

Usually, 8 mg 3 times daily.33

Prevention, for Total Body Irradiation
Oral

8 mg 1–2 hours before each fraction of radiotherapy administered each day.33

Prevention, for Single High-dose Fraction Radiation to Abdomen
Oral

8 mg 1–2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1–2 days after completion of radiotherapy.33

Prevention, for Daily Fractionated Radiation to Abdomen
Oral

8 mg 1–2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.33

Prescribing Limits

Pediatric Patients

Cancer Chemotherapy-induced Nausea and Vomiting
Prevention
IV

0.15 mg/kg (maximum 16 mg per dose).1 78 (See Cardiac Effects under Cautions.)

Adults

Cancer Chemotherapy-induced Nausea and Vomiting
Prevention
IV

0.15 mg/kg (maximum 16 mg per dose).1 78 (See Cardiac Effects under Cautions.)

Special Populations

Hepatic Impairment

Do not exceed total daily dosage of 8 mg (parenteral or oral) in patients with severe hepatic impairment (Child-Pugh score ≥10); 1 33 no experience to date with continuation beyond the first day of IV therapy.1

Renal Impairment

No dosage adjustment required, but no experience to date with continuation beyond the first day of therapy.33

Geriatric Patients

No dosage adjustment required.1 33

Cautions for Zofran

Contraindications

  • Known hypersensitivity to ondansetron or any ingredient in the formulation.1 33

  • Concomitant use with apomorphine.1 33 (See Specific Drugs under Interactions.)

Warnings/Precautions

Sensitivity Reactions

Sensitivity reactions, including anaphylactic reaction, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, and stridor, reported rarely.1 5 16 33 39

Possible hypersensitivity reactions in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.1 33

Cardiac Effects

Dose-related prolongation of QT interval and cases of torsades de pointes reported.1 33 78 79 ECG alterations including QT-interval prolongation reported mainly with IV administration.1 33

In healthy adults, IV ondansetron doses of 8 or 32 mg produced maximum mean baseline-corrected increases in QTc interval (QT interval corrected for heart rate using Fridericia’s formula) relative to placebo of 5.8 or 19.6 milliseconds, respectively.1 78 Individual IV doses should not exceed 16 mg.1 78 (See Dosage under Dosage and Administration.)

Avoid use of ondansetron in patients with congenital long QT syndrome.1 33 79

Monitor ECG in patients with electrolyte abnormalities (e.g. hypokalemia, hypomagnesemia), CHF, or bradyarrhythmias and in those receiving other drugs known to prolong the QT interval.1 33 79 Correct electrolyte abnormalities prior to IV administration of ondansetron.78

GI Precautions

Does not stimulate gastric or intestinal peristalsis; do not use as a substitute for nasogastric suction.1 33

May mask progressive ileus and/or gastric distention in patients undergoing abdominal surgery or in those with chemotherapy-induced nausea and vomiting.1 33

Phenylketonuria

Each 4- or 8-mg Zofran ODT orally disintegrating tablet contains aspartame (Nutrasweet), which is metabolized in the GI tract to provide <0.03 mg of phenylalanine per tablet.33

Specific Populations

Pregnancy

Category B.1 33

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 33 Caution advised if used in nursing women.1 33

Pediatric Use

Safety and efficacy of oral or IV ondansetron for prevention of chemotherapy-induced emesis generally comparable to that in adults.1 33

Little information available on IV use for prevention of postoperative nausea and vomiting in pediatric patients <1 month of age or for prevention of chemotherapy-induced nausea and vomiting in pediatric patients <6 months of age.1 33 Little information available on oral dosage in children ≤4 years of age.33

Because clearance is reduced in infants 1–4 months of age compared with those >4 to 24 months of age, closely monitor infants <4 months of age.1 (See Half-life under Pharmacokinetics.)

Efficacy of single 24-mg oral dose for prevention of nausea and vomiting induced by highly emetogenic chemotherapy or oral therapy for prevention of radiation-induced or postoperative nausea and vomiting not established in children <18 years of age.33

Geriatric Use

No substantial differences in safety or efficacy in patients >65 years of age relative to younger adults, but increased sensitivity cannot be ruled out.1 16 33

Hepatic Impairment

Clearance is decreased and half-life increased in patients with hepatic impairment.1 33 Use with caution and at reduced dosage in patients with severe hepatic impairment.1 15 33 (See Special Populations under Dosage and Administration.)

Common Adverse Effects

Headache, diarrhea, dizziness, constipation, fever, drowsiness/sedation, shivers, malaise/fatigue, hypoxia, pyrexia, urinary retention, pruritus.1 33

Interactions for Zofran

Substrate of CYP1A2, CYP2D6, and CYP3A4 in vitro; does not appear to induce or inhibit CYP isoenzymes.1 33

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP1A2, CYP2D6, or CYP3A4; potential pharmacokinetic interaction (altered ondansetron metabolism).1 33 Based on available data, no dosage adjustment recommended for patients on these drugs.1 33

Drugs that Prolong QT Interval

Potential additive effect on QT-interval prolongation.1 33 Monitor ECG during concomitant use.1 33 (See Cardiac Effects under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Alfentanil

No change in respiratory depressant effects of alfentanil1 33

Antacids

No effect on ondansetron bioavailability33

Apomorphine

Profound hypotension and loss of consciousness reported1 33

Concomitant use contraindicated1 33

Atracurium

No change in degree of neuromuscular blockade produced by atracurium1 33

Carbamazepine

Substantial increase in ondansetron clearance (decreased plasma concentrations and half-life)1 33

On basis of available data, no dosage adjustment recommended1 33

Carmustine

No effect on ondansetron pharmacokinetics1 33

Cisplatin

No effect on ondansetron pharmacokinetics1 33

Diuretics

May induce electrolyte disorders and increase risk of cardiac arrhythmias (e.g., QT-interval prolongation, torsades de pointes)1

Etoposide

No effect on ondansetron pharmacokinetics1 33

Methotrexate

IV ondansetron did not increase blood levels of high-dose methotrexate in pediatric patients1 33

Phenytoin

Substantial increase in ondansetron clearance (decreased plasma concentrations and half-life)1 33

On basis of available data, no dosage adjustment recommended1 33

Rifampin

Substantial increase in ondansetron clearance (decreased plasma concentrations and half-life) 1 33

On basis of available data, no dosage adjustment recommended1 33

Temazepam

No effect on temazepam pharmacokinetics or pharmacodynamics1 33

Tramadol

No pharmacokinetic interaction observed, but possible increased tramadol dosage requirements for patient-controlled analgesia1 33

Zofran Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract after oral administration.33 Mean bioavailability after administration of single 8-mg tablet is approximately 56%; increased bioavailability expected with dosages >8 mg.33 c

Peak plasma concentrations are attained approximately 1.5–2.2 hours after oral administration, approximately 25 minutes after IV infusion, or 41 minutes after IM injection.1 33 c

Commercially available oral solution and orally disintegrating tablets (4- or 8-mg doses) are bioequivalent to corresponding doses of conventional tablets.33

Food

Food slightly increases bioavailability.33

Special Populations

Extent and rate of absorption are increased in women compared with men; not known whether differences are clinically important.33

Distribution

Extent

Circulating drug distributes into erythrocytes.33

Distributed into milk in rats; not known whether distributed into human milk.33

Plasma Protein Binding

70–76%.33

Elimination

Metabolism

Extensively metabolized in the liver via hydroxylation followed by subsequent glucuronide or sulfate conjugation.33 CYP isoenzymes 1A2, 2D6, and 3A4 are involved;1 33 role of CYP2D6 is relatively minor.1

Exhibits nonlinear pharmacokinetics, possibly due to saturation of hepatic metabolism.c

Elimination Route

<5% of a dose is excreted unchanged in urine.1

Half-life

Adults: Approximately 3–3.5 hours after single 8-mg oral dose; approximately 4 hours after IV administration.1 33 c

Children and adolescents 3–18 years of age: 2.4–3 hours after IV administration.1 c

Infants 5–24 months of age: 2.9 hours after IV administration.1

Infants 1–4 months of age: 6.7 hours after IV administration.1

Special Populations

In patients with mild to moderate hepatic impairment, clearance is decreased 2-fold and half-life increased to 11.6 hours.1 33 In patients with severe hepatic impairment (Child-Pugh score ≥10), clearance is decreased 2- to 3-fold and half-life increased to 20 hours.1 33

Although renal clearance contributes minimally to overall clearance, mean plasma clearance is reduced by about 50% in patients with severe renal impairment (Clcr <30 mL/minute); reduction in clearance is variable and not consistent with an increase in half-life.1 33

In geriatric patients >75 years of age, clearance is decreased and half-life is increased to 4.5–6.2 hours.1 33

Pharmacokinetics similar in poor and in extensive metabolizers of CYP2D6 substrates.1

Stability

Storage

Oral

Conventional Tablets

Tight, light resistant containers at 2–30°C; protect from light.33

Orally Disintegrating Tablets

2–30°C.33

Solution

15–30°C; store bottles upright and protect from light.33

Parenteral

Injection

2–30°C; protect from light.1

Occasionally precipitates at the stopper/vial interface in vials stored upright; potency and safety not affected.1 If precipitate is found, vigorously shake vial to resolubilize.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Do not mix with solutions for which physical and chemical compatibility have not been established, particularly alkaline solutions, as precipitate may form.1

Solution Compatibility

Compatible

Dextrose 5% in water1 d

Dextrose 5% in water with potassium chloride 0.3%d

Dextrose 5% in sodium chloride 0.45 or 0.9%1

Mannitol 10%d

Ringer’s injectiond

Ringer’s injection, lactatedd

Sodium chloride 0.9%1 d

Sodium chloride 0.9% with potassium chloride 0.3%d

Drug Compatibility
Admixture Compatibilityd

Compatible

Cisplatin

Cyclophosphamide

Cytarabine

Dacarbazine

Doxorubicin HCl

Doxorubicin HCl with vincristine sulfate

Etoposide

Fluconazole with ranitidine HCl

Hydromorphone HCl

Meperidine HCl

Methotrexate sodium

Morphine sulfate

Tramadol HCl

Variable

Dacarbazine with doxorubicin HCl

Dexamethasone sodium phosphate

Meropenem

Methylprednisolone sodium succinate

Y-Site Compatibilityd

Compatible

Aldesleukin

Amifostine

Amikacin sulfate

Azithromycin

Aztreonam

Bleomycin sulfate

Carboplatin

Carmustine

Caspofungin acetate

Cefazolin sodium

Cefotaxime sodium

Cefoxitin sodium

Ceftazidime

Cefuroxime sodium

Chlorpromazine HCl

Cimetidine HCl

Cisatracurium besylate

Cisplatin

Cladribine

Clindamycin phosphate

Cyclophosphamide

Cytarabine

Dacarbazine

Dactinomycin

Daunorubicin HCl

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Diphenhydramine HCl

Docetaxel

Dopamine HCl

Doripenem

Doxorubicin HCl

Doxorubicin HCl liposome injection

Doxycycline hyclate

Droperidol

Etoposide

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Filgrastim

Floxuridine

Fluconazole

Fludarabine phosphate

Gallium nitrate

Gemcitabine HCl

Gentamicin sulfate

Haloperidol lactate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Ifosfamide

Imipenem–cilastatin sodium

Linezolid

Magnesium sulfate

Mannitol

Mechlorethamine HCl

Melphalan HCl

Meperidine HCl

Mesna

Methotrexate sodium

Metoclopramide HCl

Mitomycin

Mitoxantrone HCl

Morphine sulfate

Oxaliplatin

Paclitaxel

Paclitaxel with ranitidine HCl

Pentostatin

Piperacillin sodium–tazobactam sodium

Potassium chloride

Prochlorperazine edisylate

Promethazine HCl

Ranitidine HCl

Remifentanil HCl

Sodium acetate

Streptozocin

Teniposide

Thiotepa

Ticarcillin disodium–clavulanate potassium

Topotecan HCl

Vancomycin HCl

Vinblastine sulfate

Vincristine sulfate

Vinorelbine tartrate

Zidovudine

Incompatible

Acyclovir sodium

Allopurinol sodium

Aminophylline

Amphotericin B

Amphotericin B cholesteryl sulfate complex

Ampicillin sodium

Ampicillin sodium–sulbactam sodium

Amsacrine

Cefepime HCl

Furosemide

Ganciclovir sodium

Lorazepam

Methylprednisolone sodium succinate

Micafungin sodium

Pemetrexed disodium

Piperacillin sodium

Sargramostim

Sodium bicarbonate

Variable

Fluorouracil

Meropenem

Actions

  • Antiemetic activity appears to be mediated both centrally (in medullary chemoreceptor trigger zone) and peripherally (in GI tract) via inhibition of 5-HT3 receptors.27 43 44 45 47 50 51 67 68

Advice to Patients

  • For patients taking orally disintegrating tablets, importance of not removing tablet from blister until just before administering dose and of not pushing tablet through foil; importance of opening blister pack with dry hands and of placing tablet on tongue to dissolve and be swallowed with saliva.33

  • Risk of QT-interval prolongation and torsades de pointes.1 33 78 79 Importance of seeking immediate medical care if feelings of faintness, lightheadedness, irregular heartbeat, shortness of breath, or dizziness occur.1 78 79

  • Importance of informing patients with phenylketonuria that orally disintegrating tablets contain aspartame.33

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 33

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 33

  • Importance of advising patients of other important precautionary information.1 33 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ondansetron

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, orally disintegrating

4 mg*

Ondansetron Orally Disintegrating Tablets

ZofranODT

GlaxoSmithKline

8 mg*

Ondansetron Orally Disintegrating Tablets

ZofranODT

GlaxoSmithKline

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ondansetron Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

4 mg (of ondansetron) per 5 mL*

Ondansetron Hydrochloride Oral Solution

Zofran

GlaxoSmithKline

Tablets, film-coated

4 mg (of ondansetron)*

Ondansetron Hydrochloride Tablets

Zofran

GlaxoSmithKline

8 mg (of ondansetron)*

Ondansetron Hydrochloride Tablets

Zofran

GlaxoSmithKline

Parenteral

Injection, for IV use

2 mg (of ondansetron) per mL*

Ondansetron Hydrochloride Injection

Zofran

GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Ondansetron 4MG Dispersible Tablets (MYLAN): 30/$52.99 or 90/$138.97

Ondansetron 8MG Dispersible Tablets (GLENMARK PHARMACEUTICALS): 30/$40.99 or 90/$99.99

Ondansetron HCl 4MG Tablets (ACTAVIS): 30/$70.99 or 90/$186.97

Ondansetron HCl 8MG Tablets (ACTAVIS TOTOWA): 30/$39.99 or 90/$99.97

Zofran 4MG Tablets (GLAXO SMITH KLINE): 10/$245.00 or 30/$702.93

Zofran 8MG Tablets (GLAXO SMITH KLINE): 30/$1,169.91 or 90/$3,403.36

Zofran ODT 4MG Dispersible Tablets (GLAXO SMITH KLINE): 30/$659.95 or 90/$1,909.91

Zofran ODT 8MG Dispersible Tablets (GLAXO SMITH KLINE): 10/$415.97 or 30/$1,209.95

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. GlaxoSmithKline. Zofran (ondansetron hydrochloride) injection prescribing information. Research Triangle Park, NC; 2012 Jun.

2. Glaxo, Research Triangle Park, NC: Personal communication.

3. Milne RJ, Heel RC. Ondansetron: therapeutic use as an antiemetic. Drugs. 1991; 41:574-95. [PubMed 1711961]

4. Dershwitz M, Rosow CE, Di Biase PM et al. Ondansetron is effective in decreasing postoperative nausea and vomiting. Clin Pharmacol Ther. 1992; 52:96-101. [IDIS 299623] [PubMed 1385567]

5. Chen M, Tanner A, Gallo-Torres H. Anaphylactoid-anaphylactic reactions associated with ondansetron. Ann Intern Med. 1993; 119:862. [IDIS 320846] [PubMed 8379613]

6. Beck TM, Ciociola AA, Jones SE et al. Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. Ann Intern Med. 1993; 118:407-13. [IDIS 311537] [PubMed 8439113]

7. Sargent AI, Deppe SA, Chan FA. Seizure associated with ondansetron. Clin Pharm. 1993; 12:613-5. [IDIS 317861] [PubMed 8222528]

8. Herrstedt J, Sigsgaard T, Boesgaard M et al. Ondansetron plus metopimazine compared with ondansetron alone in patients receiving moderately emetogenic chemotherapy. N Engl J Med. 1993; 328:1076-80. [IDIS 312366] [PubMed 8455664]

9. Pritchard JF, Bryson JC, Kernodle AE et al. Age and gender effects on ondansetron pharmacokinetics: evaluation of healthy aged volunteers. Clin Pharmacol Ther. 1992; 41:51-5.

10. Jones AL, Hill AS, Soukop M et al. Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy. Lancet. 1991; 338:483-7. [IDIS 284480] [PubMed 1678453]

11. Scuderi P, Wetchler B, Sung YF et al. Treatment of postoperative nausea and vomiting after outpatient surgery with the 5-HT3 antagonist ondansetron. Anesthesiology. 1993; 78:15-20. [IDIS 309383] [PubMed 8424548]

12. McKenzie R, Kovac A, O’Connor T et al. Comparison of ondansetron versus placebo to prevent postoperative nausea and vomiting in women undergoing ambulatory gynecologic surgery. Anesthesiology. 1993; 78:21-8. [IDIS 309384] [PubMed 8424561]

13. Ballard HS, Bottino G, Bottino J. Ondansetron and chest pain. Lancet. 1992; 340:1107. [IDIS 304614] [PubMed 1357506]

14. Bryson JC. Clinical safety of ondansetron. Semin Oncol. 1992; 19(Suppl 15):26-32. [PubMed 1485179]

15. Castle WM, Jukes AJ, Griffiths CJ et al. Safety of ondansetron. Eur J Anaesthesiol. 1992; 9(Suppl 6):63-6. [PubMed 1735399]

16. Finn AL. Toxicity and side effects of ondansetron. Semin Oncol. 1992; 19(Suppl 10):53-60. [PubMed 1387251]

17. Smith RN. Safety of ondansetron. Eur J Cancer Clin Oncol. 1989; 25(Suppl 1):S47-50. [PubMed 2533899]

18. Krstenansky PM, Petree J, Long G. Extrapyramidal reaction caused by ondansetron. Ann Pharmacother. 1994; 28:280. [IDIS 325871] [PubMed 8173151]

19. Halperin JR, Murphy B. Extrapyramidal reaction to ondansetron. Cancer. 1992; 69:1275. [IDIS 292533] [PubMed 1531444]

20. Dobrow RB, Coppock MA, Hosenpud JR. Extrapyramidal reaction caused by ondansetron. J Clin Oncol. 1991; 9:1921. [PubMed 1833512]

21. Garcia-del-Muro X, Cardenal F, Ferrer P. Extrapyramidal reaction associated with ondansetron. Eur J Cancer. 1993; 29A:288. [PubMed 8422300]

22. Siderov J, Zalcberg J, Chambers B et al. Migraine following the use of a 5-hydroxytryptamine antagonist. Aust N Z J Med. 1993; 23:527-8. [PubMed 8297291]

23. Mitchell KE, Popkin MK, Trick W et al. Psychiatric complications associated with ondansetron. Psychosomatics. 1994; 35:161-3. [PubMed 8171176]

24. Tsidonis O. Ondansetron-induced jaundice. ASHP Midyear Clinical Meeting. Dec 6-10, 1992. Abstract No. P-411D.

25. McQueen KD, Milton JD. Multicenter postmarketing surveillance of ondansetron therapy in pediatric patients. Ann Pharmacother. 1994; 28:85-92. [IDIS 324489] [PubMed 8123969]

26. Stevens RF. The role of ondansetron in paediatric patients: a review of three studies. Eur J Cancer. 1991; 27(Suppl 1):S20-2. [PubMed 1831631]

27. De Mulder PHM, Seynaeve C, Vermorken JB et al. Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, crossover study. Ann Intern Med. 1990; 113:834-40. [IDIS 274419] [PubMed 2146911]

28. Sledge GW Jr, Einhorn L, Nagy C et al. Phase III double-blind comparison of intravenous ondansetron and metoclopramide as antiemetic therapy for patients receiving multiple-day cisplatin-based chemotherapy. Cancer. 1992; 70:2524-8. [IDIS 305314] [PubMed 1423181]

29. Grunberg SM, Lane M, Lester EP et al. Randomized double-blind comparison of three dose levels of intravenous ondansetron in the prevention of cisplatin-induced emesis. Cancer Chemother Pharmacol. 1993; 32:268-72. [PubMed 8324868]

30. Hesketh PJ, Harvey WH, Harker WG et al. A randomized, double-blind comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin-induced emesis. J Clin Oncol. 1994; 12:596-600. [IDIS 327016] [PubMed 8120559]

31. Cubeddu LX, Pendergrass K, Ryan T et al. Efficacy of oral ondansetron, a selective antagonist of 5-HT3 receptors, in the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapies. Am J Clin Oncol. 1994; 17:137-46. [IDIS 329907] [PubMed 8141105]

32. Pearman MH. Single dose intravenous ondansetron in the prevention of postoperative nausea and vomiting. Anaesthesia. 1994; 49(Suppl):11-5. [IDIS 325312] [PubMed 8129156]

33. GlaxoSmithKline. Zofran (ondansetron hydrochloride) tablets, Zofran ODT (ondansetron) orally disintegrating tablets, and Zofran (ondansetron hydrochloride) oral solution prescribing information. Research Triangle Park, NC; 2011 Sept.

34. Rust M, Cohen LA. Single oral dose ondansetron in the prevention of postoperative nausea and emesis. Anaesthesia. 1994; 49(Suppl):16-23. [IDIS 325313] [PubMed 8129157]

35. Kris MG, Gralla RJ, Clark RA et al. Dose-ranging evaluation of the serotonin antagonist GR-C507/75 (GR38032F) when used as an antiemetic in patients receiving anticancer chemotherapy. J Clin Oncol. 1988; 6:659-62. [PubMed 2965755]

36. Rosso R, Campora E, Cetto G et al. Oral ondansetron (GR 38032F) for the control of acute and delayed cyclophosphamide-induced emesis. Anticancer Res. 1991; 11:937-40. [PubMed 1829602]

37. Smith DB, Newlands ES, Rustin GJS et al. A phase I/II study of the 5-HT3 antagonist GR38032F in the anti-emetic prophylaxis of patients receiving high-dose cisplatin chemotherapy. Cancer Chemother Pharmacol. 1990; 25:291-4. [PubMed 1688516]

38. Kaasa S, KvalQy S, Dicato MA et al. A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, double-blind study. Eur J Cancer. 1990; 26:311-4. [PubMed 2141487]

39. Grunberg SM, Stevenson LL, Russell CA et al. Dose ranging phase I study of the serotonin antagonist GR38032F for prevention of cisplatin-induced nausea and vomiting. J Clin Oncol. 1989; 7:1137-41. [PubMed 2526864]

40. Hesketh PJ, Murphy WK, Lester EP et al. GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis. J Clin Oncol. 1989; 7:700-5. [PubMed 2523957]

41. Einhorn LH, Nagy C, Werner K et al. Ondansetron: a new antiemetic for patients receiving cisplatin chemotherapy. J Clin Oncol. 1990; 8:731-5. [PubMed 2138214]

42. Baltzer L, Kris MG, Hinkley L et al. Reversible electrocardiographic interval prolongations following the specific serotonin antagonists ondansetron (OND) and dolasetron mesylate (DM): a possible drug class effect without sequelae? Proc Am Soc Clin Oncol. 1994; 13:433. Abstract No. 1489.

43. McKeage MJ. Comparative adverse effect profile of platinum drugs. Drug Saf. 1995; 13:228-44. [PubMed 8573296]

44. Cubeddu LX, Hoffmann IS. Participation of serotonin on early and delayed emesis induced by initial and subsequent cycles of cisplatinum-based chemotherapy: effects of antiemetics. J Clin Pharmacol. 1993; 33:691-7. [IDIS 319277] [PubMed 7691898]

45. Hesketh PJ, Gandara DR. Serotonin antagonists: a new class of antiemetic agents. J Natl Cancer Inst. 1991; 83:613-20. [PubMed 1850806]

46. du Bois A, Meerpohl HG, Vach W et al. Course, patterns, and risk-factors for chemotherapy-induced emesis in cisplatin pretreated patients: a study with ondansetron. Eur J Cancer. 1992; 28:450-7. [PubMed 1534250]

47. Gebbia V, Cannata G, Testa A et al. Ondansetron versus granisetron in the prevention of chemotherapy- induced nausea and vomiting. Results of a prospective randomized trial. Cancer. 1994; 74:1945-52. [IDIS 336138] [PubMed 8082100]

48. Perez EA. Review of the preclinical pharmacology and comparative efficacy of 5-hydroxytryptamine-3 receptor antagonists for chemotherapy-induced emesis. J Clin Oncol. 1995; 13:1036-43. [IDIS 344879] [PubMed 7707101]

49. Ruff P, Paska W, Goedhals L et al for the Ondansetron and Granisetron Emesis Study Group. Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced acute emesis: a multicentre double-blind, randomised, parallel-group study. Oncology. 1994; 51:113-8. [PubMed 8265095]

50. Gralla RJ. Adverse effects of treatment: antiemetic therapy. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia: J.B. Lippincott Company; 1993:2338-48.

51. Kris MG, Pisters KM, Hinkley L. Delayed emesis following anticancer chemotherapy. Support Care Cancer. 1994; 2:297- 300. [PubMed 8000726]

52. Italian Group for Antiemetic Research. Ondansetron + dexamethasone vs metoclopramide + dexamethasone + diphenhydramine in prevention of cisplatin-induced emesis. Lancet. 1992; 340:96-99. [IDIS 298926] [PubMed 1352024]

53. du Bois A, Vach W, Thomssen C et al. Comparison of emetogenic potential between cisplatin and carboplatin in combination with akylating agents. Acta Oncol. 1994; 33:531-5. [PubMed 7917367]

54. Smith DB, Newlands ES, Rustin GJS et al. Comparison of ondansetron and ondansetron plus dexamethasone as antiemetic prophylaxis during cisplatin-containing chemotherapy. Lancet. 1991; 338:487-90. [IDIS 284481] [PubMed 1714532]

55. Anon. Ondansetron vs dexamethasone for chemotherapy-induced emesis. Lancet. 1991; 338:478-9. [PubMed 1714531]

56. Navari R, Gandara D, Hesketh P et al. Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. J Clin Oncol. 1995; 13:1242-8. [IDIS 347756] [PubMed 7738628]

57. Marty M. A comparison of granisetron as a single agent with conventional combination antiemetic therapies in the treatment of cytostatic-induced emesis. The Granisetron Study Group. Eur J Cancer. 1992; 28A(Suppl 1):S12-6.

58. Ohmatsu H, Eguchi K, Shinkai T et al. A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin. Jpn J Cancer Res. 1994; 85:1151-8. [PubMed 7829401]

59. Heron JF, Goedhals L, Jordaan JP et al. Oral granisetron alone and in combination with dexamethasone: a double-blind randomized comparison against high-dose metoclopramide plus dexamethasone in prevention of cisplatin- induced emesis. The Granisetron Study Group. Ann Oncol. 1994; 5:579-84. [PubMed 7993831]

60. The Granisetron Study Group. The antiemetic efficacy and safety of granisetron compared with metoclopramide plus dexamethasone in patients receiving fractionated chemotherapy over 5 days. J Cancer Res Clin Oncol. 1993; 119:555-9. [PubMed 8392077]

61. Cunningham D, Hill M, Dicato M et al. Optimal anti-emetic therapy for cisplatin induced emesis over repeat courses. Proc Ann Meet Am Soc Clin Oncol. 1994; 13:A1553.

62. Tyson LB, Gralla RJ, Clark RA et al. Combination antiemetic trials with metoclopramide. Proc Am Soc Clin Oncol. 1983; 2:91.

63. Ahn MJ, Lee JS, Lee KH et al. A randomized double-blind trial of ondansetron alone versus in combination with dexamethasone versus in combination with dexamethasone and lorazepam in the prevention of emesis due to cisplatin-based chemotherapy. Am J Clin Oncol. 1994; 17:150-6. [IDIS 329909] [PubMed 8141107]

64. Bruera ED, Roca E, Cedaro L et al. Improved control of chemotherapy- induced emesis by the addition of dexamethasone to metoclopramide in patients resistant to metoclopramide. Cancer Treat Rep. 1983; 67:381-3. [IDIS 171263] [PubMed 6342770]

65. Malik IA, Khan WA, Qazilbash M et al. Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial. Am J Clin Oncol. 1995; 18:170-5. [IDIS 344756] [PubMed 7900711]

66. Clerico M, Bertetto O, Cardinali C et al. Antiemetic activity of lorazepam in the prophylactic treatment of vomiting induced by cisplatin: a double-blind placebo controlled study with cross-over design. Ann Oncol. 1992; 3(Suppl 5):188.

67. Plosker GL, Goa KL. Granisetron: a review of its pharmacological properties and therapeutic use as an antiemetic. Drugs. 1991; 42:805-24. [PubMed 1723376]

68. Grunberg SM, Hesketh PJ. Control of chemotherapy-induced emesis. N Engl J Med. 1993; 329:1790-6. [IDIS 322575] [PubMed 8232489]

69. Mitchelson F. Pharmacological agents affecting emesis: a review (part I). Drugs. 1992; 43:295-315. [PubMed 1374316]

70. Aapro MS. 5-HT3 receptor antagonists: an overview of their present status and future potential in cancer therapy- induced emesis. Drugs. 1991; 42:551-68. [PubMed 1723361]

71. American Medical Association Council on Scientific Affairs. Aspartame: review of safety issues. JAMA. 1985; 254:400-2. [IDIS 202002] [PubMed 2861297]

72. Gossel TA. A review of aspartame: characteristics, safety and uses. US Pharm. 1984; 9:26,28-30.

73. Food and Drug Administration. Aspartame as an inactive ingredient in human drug products; labeling requirements. Proposed rule. [21 CFR Part 201] Fed Regist. 1983; 48:54993-5. (lDIS 178728)

74. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; aspartame. Final rule. [21 CFR Part 172] Fed Regist. 1983; 48:31376-82. (IDIS 172957)

75. Anon. Aspartame and other sweeteners. Med Lett Drugs Ther. 1982; 24:1-2. [PubMed 7054648]

76. Khalil SN, Roth AG, Cohen IT et al. A double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia. Anesth Analg. 2005; 101:356-51. [PubMed 16037143]

77. Kris MG, Hesketh PJ, Somerfield MR et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol. 2006; 24:1-16. [PubMed 16330665]

78. US Food and Drug Administration. FDA drug safety communication: New information regarding QT prolongation with ondansetron (Zofran). Rockville, MD; 2012 Jun 29. From the FDA website.

79. US Food and Drug Administration. FDA drug safety communication: Abnormal heart rhythms may be associated with use of Zofran (ondansetron). Rockville, MD; 2011 Sept 15. From the FDA website.

80. Charbit B, Alvarez JC, Dasque E et al. Droperidol and ondansetron-induced QT interval prolongation: a clinical drug interaction study. Anesthesiology. 2008; 109:206-12. [PubMed 18648229]

81. Charbit B, Albaladejo P, Funck-Brentano C et al. Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology. 2005; 102:1094-100. [PubMed 15915019]

c. GlaxoSmithKline, Research Triangle Park, NC; Personal communication.

d. Trissel LA. Handbook on injectable drugs. 16th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2011:1173-84.

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