Ondansetron 

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Medication Safety Issues

Sound-alike/look-alike issues:

Ondansetron may be confused with dolasetron, granisetron, palonosetron

Zofran® may be confused with Zantac®, Zosyn®

Pronunciation

(on DAN se tron)

U.S. Brand Names

 Zofran®
 Zofran® ODT

Index Terms

 GR38032R
 Ondansetron Hydrochloride
Generic Available

Yes

Canadian Brand Names

 Apo-Ondansetron®
 Dom-Ondansetron
 Gen-Ondansetron
 JAMP-Ondansetron
 Mint-Ondansetron
 Mylan-Ondansetron
 Novo-Ondansetron
 Ondansetron Injection
 Ondansetron-Omega
 PHL-Ondansetron
 PMS-Ondansetron
 RAN™-Ondansetron
 ratio-Ondansetron
 Sandoz-Ondansetron
 Zofran®
 Zofran® ODT

Pharmacologic Category

 Antiemetic
 Selective 5-HT3 Receptor Antagonist

Pharmacologic Category Synonyms

 5-HT3 Receptor Antagonist

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

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-HT3antagonists. I.V.
formulations of 5-HT3 antagonists have more association with ECG interval
changes, compared to oral formulations.

Disease-related concerns:

• 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).

Special populations:
• Pediatrics: Safety and efficacy have not been established in children <1 month
of age.

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, tachycardia, vascular occlusive
events

Postmarketing and/or case reports: Anaphylactoid reactions, angioedema,

arrhythmia, blindness (transient/following infusion; lasting ?48 hours), blurred
vision (transient/following infusion), bradycardia, cardiopulmonary arrest,
dyspnea, dystonic reaction, electrocardiographic alterations (second-degree heart
block and ST-segment depression), flushing, hiccups, hypersensitivity reaction,
hypotension, laryngeal edema, laryngospasm, oculogyric crisis, palpitation,
premature ventricular contractions (PVC), QT interval increased, shock, stridor,
supraventricular tachycardia, syncope, urticaria, ventricular arrhythmia

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4
(major); Inhibits CYP1A2 (weak), 2C9 (weak), 2D6 (weak)

Drug Interactions

Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive

effect of Apomorphine. Risk X: Avoid combination

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
Ethanol/Nutrition/Herb Interactions

Food: Food increases the extent of absorption. The Cmax and Tmax do not change
much.

Herb/Nutraceutical: St John's wort may decrease ondansetron levels.

Storage

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

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%; Rectal: 58% to 74%

Half-life elimination: Children <15 years: 2-7 hours; Adults: 3-6 hours

Mild-to-moderate hepatic impairment: Adults: 12 hours

Severe hepatic impairment (Child-Pugh C): Adults: 20 hours

Time to peak: Oral: ~2 hours

Excretion: Urine (44% to 60% as metabolites, 5% to 10% as unchanged drug);

feces (?25%)

Dosage

Note: Studies in adults have shown a single daily dose of 8-12 mg I.V. or 8-24
mg orally to be as effective as mg/kg dosing, and should be considered
for all patients whose mg/kg dose exceeds 8-12 mg I.V.; oral solution and ODT
formulations are bioequivalent to corresponding doses of tablet formulation

Children:

I.V.:

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 or0.45 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 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:

Highly-emetogenic agents/single-day therapy: 24 mg given 30 minutes prior to

the start of therapy

Moderately-emetogenic agents: 8 mg every 12 hours beginning 30 minutes

before chemotherapy, continuously for 1-2 days after chemotherapy completed
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.

The I.V. preparation has been successful when administered orally.

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 reduce the incidence of nausea and vomiting. Do not take
any other medication for nausea and vomiting with this medication unless
approved by prescriber. If this medication is given by intravenous infusion you
will be monitored during infusion. Report immediately any chest pain,
respiratory difficulty, pain or itching at infusion site. Self-administered oral
doses must be taken exactly as directed. If self-administered, take as directed.
May cause headache, drowsiness, or dizziness (request assistance when getting
up or changing position and do not perform activities requiring alertness
[including driving] until response to drug is known). Report chest pain or
palpitations; persistent headache; excessive drowsiness; fever; or changes in
elimination patterns (constipation or diarrhea) or other adverse effects. Breast-
feeding precaution: Consult prescriber if you are or intend to breast-feed.

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.

Geriatric Considerations

Elderly have a slightly decreased hepatic clearance rate. This does not, however,
require a dose adjustment.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary

flow resumes upon discontinuation).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

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). Follow specific administration specifics
according to formulation. Note: Oral and I.V. doses have different schedules and
should not be administered on "PRN" basis. Assess therapeutic effectiveness and
adverse reactions on a regular basis. Teach patient possible side effects and
adverse symptoms to report.

Dosage Forms

Excipient information presented when available (limited, particularly for

generics); consult specific product labeling. [DSC] = Discontinued product

Infusion, premixed in D5 [preservative free]: 32 mg (50 mL)

Zofran®: 32 mg (50 mL) [DSC]

Infusion, premixed in sodium chloride [preservative free]: 32 mg (50 mL)

Injection, solution: 2 mg/mL (2 mL, 20 mL)

Zofran®: 2 mg/mL (2 mL, 20 mL)

Injection, solution [preservative free]: 2 mg/mL (2 mL)

Solution, oral: 4 mg/5 mL (50 mL)

Zofran®: 4 mg/5 mL (50 mL) [contains sodium benzoate; strawberry flavor]

Tablet: 4 mg; 8 mg

Zofran®: 4 mg; 8 mg

Tablet, orally disintegrating: 4 mg; 8 mg

Zofran® ODT: 4 mg, 8 mg [each strength contains phenylalanine <0.03

mg/tablet; strawberry flavor]

Pricing: U.S. (www.drugstore.com)

Tablet, orally-disintegrating (Ondansetron)
4 mg (30): $52.99

8 mg (30): $39.99

Tablet, orally-disintegrating (Zofran ODT)

4 mg (30): $659.96

Tablets (Ondansetron HCl)

4 mg (30): $39.99

8 mg (30): $39.99

Tablets (Zofran)

4 mg (10): $244.62

8 mg (30): $1169.92

24 mg (10): $1008.40

Extemporaneously Prepared

A 0.8 mg/mL syrup may be made by crushing ten 8 mg tablets; flaking of the
tablet coating occurs. Mix thoroughly with 50 mL of the suspending vehicle,
Ora-Plus® (Paddock), in 5 mL increments. Add sufficient volume of any of the
following syrups: Cherry syrup USP, Syrpalta® (Humco), Ora-Sweet®
(Paddock), or Ora-Sweet® Sugar-Free (Paddock) to make a final volume of 100
mL. Stability is 42 days refrigerated.

Trissel LA, “Trissel's Stability of Compounded Formulations,” American

Pharmaceutical Association, 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. Divide the
tablet weight by the DF. Subtract the weight of base displaced from the
calculated weight of base required for each suppository. Grind the ondansetron
tablets to a fine powder in a mortar. 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 under refrigeration.

Allen LV, “Ondansetron Suppositories,” US Pharm, 20(7):84-6.