Version May 2024
Chemotherapy-induced nausea and vomiting, prevention:
Note: Use in combination with or without dexamethasone and aprepitant or fosaprepitant depending upon patient age, chemotherapy emetogenic potential, and drug-interaction profile; dosing regimens variable, refer to specific protocols or institutional guidelines (Ref).
Multiple-daily dose regimen (high, moderate, low emetic potential):
Weight-directed dosing:
Infants, Children, and Adolescents: IV, Oral: 0.15 mg/kg/dose (5 mg/m2/dose); maximum single dose: 16 mg/dose; administer first dose before the start of chemotherapy and then every 4 to 12 hours, not to exceed 3 doses; maximum daily dose: 0.45 mg/kg/day or 32 mg/day; whichever is less; higher emetogenic potential chemotherapy will require more frequent administration (Ref).
Fixed dosing:
Children 4 to 11 years: Oral: 4 mg beginning 30 minutes before chemotherapy; repeat 4 and 8 hours after initial dose, then 4 mg every 8 hours for 1 to 2 days after chemotherapy completed.
Children ≥12 years and Adolescents: Oral: 8 mg beginning 30 minutes before chemotherapy; repeat dose 8 hours after initial dose, then 8 mg every 12 hours for 1 to 2 days after chemotherapy completed.
Single-daily dose regimen (low, moderate, or highly emetogenic potential): Limited data available:
Infants, Children, and Adolescents: IV: 0.3 to 0.45 mg/kg/dose once daily; maximum dose: 16 mg/dose (Ref).
Gastroenteritis, acute; treatment: Limited data available (Ref):
IV: Infants and Children: IV: 0.15 or 0.3 mg/kg/dose once; maximum dose: 16 mg/dose (Ref).
Oral: Note: May repeat dose if patient vomits within 15 minutes (Ref).
Infants ≥3 months, Children, and Adolescents:
<15 kg: Oral: 0.2 mg/kg/dose once (Ref).
15 to 30 kg: Oral: 4 mg once (Ref).
>30 kg: Oral: 8 mg once (Ref).
Postoperative nausea and vomiting, prevention: Note: Administer immediately before or following induction of anesthesia, or postoperatively if the patient is symptomatic. Repeat doses administered in response to inadequate control of nausea/vomiting from preoperative doses are generally ineffective (Ref).
Infants and Children: IV: 0.05 to 0.1 mg/kg/dose as a single dose; maximum dose: 4 mg/dose (Ref).
Adolescents: IM, IV: 4 mg/dose as a single dose (Ref).
Radiation-induced nausea and vomiting, prevention: Limited data available:
Weight-directed dosing: Infants ≥5 months, Children, and Adolescents: Oral: 0.2 mg/kg/dose (maximum dose: 8 mg/dose) administered every 8 hours throughout total body irradiation (TBI) prior to hematopoietic stem cell transplant (HSCT) (n=68; mean age: 6.7 years; range: 5 months to 20 years); doses were generally rounded to 4 mg/dose in children 4 to 11 years and 8 mg/dose in children ≥12 years and adolescents (Ref).
Alternate weight-based dosing: Children and Adolescents: Oral: 0.15 mg/kg/dose administered 3 to 4 times daily throughout TBI (n=33; mean age: 9 years; range: 13 months to 16 years) (Ref).
Fixed dose: Note: Derived from rounding weight-based (0.2 mg/kg/dose) doses (Ref).
Children 4 to 11 years: Oral: 4 mg every 8 hours throughout TBI prior to HSCT.
Children ≥12 years and Adolescents: Oral: 8 mg every 8 hours throughout TBI prior to HSCT.
Alternate fixed-dosing: Children ≥9 years and Adolescents: Oral: 8 mg every 12 hours on days of TBI prior to bone marrow transplantation (age range: 9 to 67 years; median age range: 39 to 49 years). Note: Administered in combination with dexamethasone (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: IV, Oral: No dose adjustments likely to be necessary, as clearance by the kidney accounts for only 5% of total clearance (Ref).
Infants, Children, and Adolescents: There are no pediatric-specific recommendations; based on experience in adult patients, no adjustment may be necessary for mild to moderate hepatic impairment; for severe impairment, dosing adjustment suggested.
(For additional information see "Ondansetron: Drug information")
Dosage guidance:
Safety: Single IV doses >16 mg are no longer recommended due to the potential for QT prolongation (Ref). Avoid use in patients with congenital long-QT syndrome.
Carcinoid syndrome- associated diarrhea, severe, refractory (alternative agent) (off-label use): Based on limited data (case reports):
Oral: 8 mg 3 times daily (Ref) or 8 mg twice daily for 3 days, followed by a maintenance dose of 4 to 8 mg/day for 4 to 12 weeks (Ref).
IV: 4 to 8 mg every 8 hours (Ref).
Chemotherapy-induced nausea and vomiting, prevention:
Single-day IV chemotherapy regimens:
Highly emetogenic chemotherapy (>90% risk of emesis [eg, cisplatin, breast cancer regimens that include an anthracycline combined with cyclophosphamide]):
Day of chemotherapy: Administer prior to chemotherapy and in combination with a neurokinin 1 (NK1) receptor antagonist, dexamethasone, and olanzapine (Ref).
IV: 8 mg or 0.15 mg/kg as a single dose (Ref). Maximum: 16 mg/dose (Ref).
Oral:
Tablet formulations and oral solution: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration (Ref) or 24 mg as a single dose (Ref).
Oral soluble film (Zuplenz: discontinued in the United States for >1 year): 24 mg (three 8 mg doses given together) as a single dose (Ref).
Post-chemotherapy days: 5-HT3 receptor antagonist use is not necessary (other components of the antiemetic regimen are administered) (Ref).
Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Carboplatin-based regimens:
Day of chemotherapy: Administer prior to chemotherapy and in combination with an NK1 receptor antagonist and dexamethasone (Ref).
IV: 8 mg or 0.15 mg/kg as a single dose (Ref). Maximum: 16 mg/dose (Ref).
Oral: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration (Ref).
Post-chemotherapy days: 5-HT3 receptor antagonist use is not necessary (other components of the antiemetic regimen may be administered) (Ref).
Moderately emetogenic chemotherapy (30% to 90% risk of emesis): Non-carboplatin-based regimens (alternative agent):
Note: ASCO guidelines and MASCC/ESMO guidelines do not state a preference for which 5-HT3 receptor antagonist should be used in this setting; however, palonosetron may be preferred (Ref).
Day of chemotherapy: Administer prior to chemotherapy and in combination with dexamethasone (Ref).
IV: 8 mg or 0.15 mg/kg as a single dose (Ref). Maximum: 16 mg/dose (Ref).
Oral: 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy administration (Ref).
Post-chemotherapy days: 5-HT3 receptor antagonist use is not necessary (other components of the antiemetic regimen may be administered) (Ref); however, if a first-generation 5-HT3 receptor antagonist (eg, ondansetron, granisetron) was used on day 1 of chemotherapy rather than palonosetron, the first-generation 5-HT3 receptor antagonist may be continued for post-chemotherapy emetic prophylaxis on days 2 and 3 (Ref).
Low emetogenic risk (10% to 30% risk of emesis):
Note: Single-agent ondansetron is an option for prophylaxis (Ref).
Day of chemotherapy:
IV: 8 mg as a single dose prior to chemotherapy (Ref).
Oral (off-label): 8 mg as a single dose prior to chemotherapy (Ref).
Post-chemotherapy days: Prophylaxis is not necessary on subsequent days (Ref).
Minimal emetogenic risk (<10% risk of emesis): Routine antiemetic prophylaxis is not generally necessary (Ref).
High-dose chemotherapy with stem or bone marrow transplant:
Day of chemotherapy: Administer prior to chemotherapy and in combination with a neurokinin 1 (NK1) receptor antagonist, dexamethasone, with or without olanzapine (Ref).
IV: 8 mg or 0.15 mg/kg as a single dose (Ref). Maximum: 16 mg/dose (Ref).
Oral: 24 mg as a single dose (Ref).
Oral chemotherapy agents:
High/moderate emetogenic risk oral agent (≥30% risk of emesis): Oral: 8 to 16 mg/day administered before chemotherapy and continued daily (Ref).
Low/minimal emetogenic risk oral agent (<30% risk of emesis): Oral: 8 to 16 mg/day on an as-needed basis only (Ref).
Gastroparesis, symptomatic treatment of nausea and vomiting (alternative agent) (off-label use):
Note: For patients with persistent symptoms refractory to prokinetic therapy. No data available; recommendations for use and dose are based on expert opinion.
Oral: 4 to 8 mg 3 times daily (Ref).
Nausea and/or vomiting, acute, severe (off-label use):
Note: Use has primarily been evaluated in patients with undifferentiated nausea/vomiting presenting to the emergency department; however, may also use for nausea/vomiting due to viral gastroenteritis, acute mountain sickness, cyclical vomiting syndrome, palliative care, and a variety of other medical conditions associated with severe, self-limiting acute nausea/vomiting (Ref).
Oral, IV, IM: 4 to 8 mg as a single dose (Ref); may repeat 4 to 8 mg every 4 to 8 hours as needed (Ref). Note: For parenteral therapy, IV administration is preferred over IM when possible (Ref).
Nausea and vomiting, pregnancy associated, severe or refractory (off-label use):
Note: May be considered for adjunctive treatment of nausea and vomiting when symptoms persist following initial pharmacologic therapy (Ref).
Patients without hypovolemia:Oral, IV (bolus): 4 mg every 8 hours, as needed, added to current treatment regimen (Ref). If necessary, some experts increase to a maximum of 8 mg/dose (Ref).
Patients with hypovolemia:
Note: For patients with persistent symptoms despite intravenous fluid replacement:
IV: 8 mg administered over 15 minutes every 12 hours, added to current treatment regimen (Ref). Some experts use 4 to 8 mg administered as an IV bolus every 8 hours until stabilization (Ref).
Postoperative nausea and vomiting, prevention:
Moderate- to high-risk patients:
Note: In patients at moderate risk, may combine ondansetron with other prophylactic interventions (eg, another antiemetic agent from a different pharmacologic class, modification of anesthetic technique, acupuncture); in patients at high risk, combine 3 or more interventions (Ref).
Usual dose: IV: 4 mg as a single dose at the end of surgery (Ref).
Alternative strategy: Oral (oral disintegrating tablet or oral soluble film [Zuplenz: discontinued in the United States for >1 year]): 8 mg as a single dose given 30 to 60 minutes prior to surgery (Ref).
Low-risk patients:Although prophylaxis is not always indicated in low-risk patients, consensus guidelines acknowledge that some experts may administer an antiemetic in these patients; however, clinicians are also advised that this strategy comes with the potentially unnecessary risk of rare adverse effects (Ref). If ondansetron is given, the dosing is the same as for moderate- to high-risk patients.
Post-discharge management in high-risk patients: Limited data available; dosage regimen studied in a single clinical trial:
Oral (oral disintegrating tablet or oral soluble film [Zuplenz: discontinued in the United States for >1 year]): 8 mg to be taken on discharge and in the morning of postoperative days 1 and 2 (Ref).
Postoperative nausea and vomiting, treatment or rescue therapy (off-label use):
Note: Rescue therapy should always include an antiemetic from a different class than the one used for prophylaxis, unless a potentially inadequate dose was initially administered or the effect of the first drug has worn off (>6 hours since initial dose for most 5-HT3 receptor antagonists) (Ref). However, some experts do not recommend repeat administration of a 5-HT3 antagonist unless no alternatives are available for rescue (Ref).
IV: 4 mg as a single dose when a prophylactic agent was not utilized (treatment) or following failure of an agent utilized as prophylaxis (rescue therapy) (Ref).
Oral (oral disintegrating tablet or oral soluble film [Zuplenz: discontinued in the United States for >1 year]): 4 or 8 mg as a single dose when a prophylactic agent was not utilized (treatment) or following failure of an agent utilized as prophylaxis (rescue therapy) (Ref).
Radiation therapy–associated nausea and vomiting, prevention:
High-emetogenic risk radiation therapy (total body irradiation):
Radiation day(s):
IV (off-label): 8 mg or 0.15 mg/kg (maximum: 16 mg/dose)(Ref) once daily or twice daily prior to each fraction of radiation; administer in combination with dexamethasone (Ref).
Oral: 8 mg once daily or twice daily administered 1 to 2 hours prior to each fraction of radiation; administer in combination with dexamethasone (Ref) or, in one clinical trial of 4 days of hyperfractionated total body irradiation, 8 mg (without dexamethasone) was administered 1.5 hours prior to every fraction of radiation (3 times daily for the first 3 days and twice daily on day 4) (Ref).
Post-radiation days:
IV (off-label), Oral: The appropriate duration of therapy following radiotherapy days is not well defined; ASCO guidelines recommend continuing ondansetron once daily or twice daily on the day after each day of radiation (Ref).
Moderate-emetogenic risk radiation therapy (upper abdomen, craniospinal irradiation) (off-label use):
Radiation day(s):
IV (off-label): 8 mg or 0.15 mg/kg (maximum: 16 mg/dose [manufacturer's labeling]) once daily or twice daily prior to each fraction of radiation; may administer with or without dexamethasone before the first 5 fractions (Ref).
Oral: 8 mg once daily or twice daily administered 1 to 2 hours prior to each fraction of radiation; may administer with or without dexamethasone before the first 5 fractions (Ref) or, in clinical trials involving upper abdomen radiation (high-dose single exposure or multiple-day fractionated course), 8 mg 3 times daily (without dexamethasone) has been given; doses were administered 1 to 2 hours prior to radiation therapy (Ref).
Low- (brain, head and neck, thorax, pelvis) to minimal- (extremities, breast) emetogenic risk radiation therapy:Routine prophylaxis not recommended; however, may use as rescue therapy using the following dosing with consideration of using prophylactically for the remainder of radiation therapy (Ref).
IV: 8 mg or 0.15 mg/kg (Ref) (maximum: 16 mg/dose (Ref)).
Oral: 8 mg (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV, Oral: No dose adjustments likely to be necessary, as clearance by the kidney accounts for only 5% of total clearance (Roila 1995; manufacturer’s labeling). Unlikely to be significantly dialyzed due to relatively high volume of distribution and plasma protein binding (Ref).
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment (Child-Pugh class C):
IV: Day 1: Maximum daily dose: 8 mg; however, according to the manufacturer, there is no experience beyond first-day administration (has not been studied beyond day 1)
Oral: Maximum daily dose: 8 mg
Ondansetron may commonly cause constipation (Ref). Rare cases of intestinal obstruction have also been reported (Ref).
Mechanism: Likely due to blockade of 5-HT3 gut receptors which results in decreased motility (Ref). May also occur as a result of decreased colonic transit time (Ref) and inhibition of postprandial increase in tone (Ref).
Onset: Varied; one reported case of constipation occurred the same day as oral ondansetron administration; intestinal obstruction resulted approximately 2 weeks after continuous twice daily dosing (Ref).
Risk factors:
• Preexisting liver disease (Ref)
Headache is the most reported adverse reaction with ondansetron (Ref). Additional doses and movement (with or without postural changes) have been associated with worsening (Ref). Severe headache has led to discontinuation in reported cases (Ref).
Onset: Rapid; severe headache reported to occur within minutes of administration, often lasting minutes to hours. There have been multiple case reports of children experiencing throbbing headaches for several days following ondansetron and chemotherapy (Ref). One patient reported onset of severe headache occurring within 2 hours of the first dose and continued to occur every 12 hours following repeated administration (Ref).
Risk factors:
• Personal or family history of migraine (Ref)
• Concurrent use of propofol and/or fentanyl (Ref)
• Higher doses (potential risk factor) (Ref)
Immediate hypersensitivity reactions may occur with ondansetron, including urticaria, angioedema, hypotension, bronchospasm, dyspnea, and anaphylaxis (Ref). Some patients may only present with hypotension, without any accompanying symptoms (Ref). Patients may have more severe reactions on subsequent exposure (Ref).
Mechanism: Non-dose-related; immunologic; likely IgE-mediated (Ref); may be the result of direct mast cell stimulation (in some patients without previous exposure) (Ref).
Onset: Rapid; immediate hypersensitivity reactions generally occur within 1 hour of administration, but may occur up to 6 hours after exposure (Ref). Reactions usually occur after the first dose during the second or third course of chemotherapy (Ref).
Risk factors:
• Adults with cancer (Ref); however, a few isolated cases have been reported in children (Ref)
• IV route of administration; however, anaphylaxis following sublingual administration has been reported (Ref)
• Cross-reaction between serotonin 5-HT3 antagonists has been described in limited case reports (Ref)
Increases in ECG intervals (eg, PR, QRS duration, JT); prolonged QT interval on ECG; and bradycardia have been observed with ondansetron (Ref). Cases of ventricular arrhythmias and torsades de pointes have also been reported. Rare cases of fatalities have occurred even at low doses (Ref).
Mechanism: QT prolongation may occur due to HERG K+ channel-blockade (Ref). Suppression of autonomic reflexes may contribute to bradycardia, hypotension, and tachyarrhythmias (Ref).
Onset: Rapid; usually occurs 1 to 2 hours after administration (Ref); however, QT prolongation peaks have been observed within ~5 to 15 minutes following administration (Ref). QTc intervals >500 ms have been recorded within 15 minutes after administration (Ref). May persist >2 hours from administered dose (Ref).
Risk factors:
• IV route of administration (Ref)
• Single doses >16 mg IV (Ref); however, risk should be considered even with low IV doses (Ref)
• Concomitant medications that prolong the QT interval (Ref)
• Females (Ref)
• Hypothermia (Ref)
• Concomitant volatile anesthetics or cumulative high-dose anthracycline therapy (Ref)
• Underlying heart disease including heart failure or acute coronary syndromes (Ref)
• Electrolyte abnormalities (eg, hypokalemia, hypomagnesemia) (Ref)
• History of QT prolongation, bradycardia, tachycardia, or cardiac rhythm disorders (especially ventricular arrhythmia) (Ref)
• Patients receiving ondansetron following anesthesia, while in the intensive care unit, or during hospital admission (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence reported in adult patients unless otherwise specified.
>10%:
Gastrointestinal: Constipation (9% to 11%) (table 1)
|
Drug (Ondansetron) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Ondansetron) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
9% |
0.4% |
8 mg twice daily |
Oral |
Chemotherapy-induced nausea and vomiting |
242 |
262 |
|
11% |
N/A |
N/A |
Injection |
N/A |
N/A |
N/A |
Nervous system: Fatigue (oral: ≤13%), headache (9% to 24%) (table 2), malaise (oral: ≤13%)
|
Drug (Ondansetron) |
Comparator (Metoclopramide) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Ondansetron) |
Number of Patients (Metoclopramide) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
24% |
N/A |
13% |
8 mg twice daily |
Oral |
Chemotherapy-induced nausea and vomiting |
242 |
N/A |
262 |
|
17% |
7% |
15% |
0.15 mg/kg x 3 |
Injection |
Chemotherapy-induced nausea and vomiting |
419 |
156 |
34 |
|
17% |
N/A |
14% |
4 mg single dose |
IV |
Postoperative nausea and vomiting |
547 |
N/A |
547 |
|
9% |
N/A |
5% |
16 mg single dose |
Oral |
Postoperative nausea and vomiting |
550 |
N/A |
531 |
1% to 10%:
Dermatologic: Pruritus (2% to 5%), skin rash (1%)
Gastrointestinal: Diarrhea (oral: 6%; IV: children 1 to 24 months of age: 2%)
Genitourinary: Gynecologic disease (oral: 7%), urinary retention (oral: 5%)
Hepatic: Increased serum alanine aminotransferase (>2 times ULN: 1% to 5%; transient), increased serum aspartate aminotransferase (>2 times ULN: 1% to 5%; transient)
Hypersensitivity: Anaphylaxis (<2%) (Fernando 2009)
Local: Injection site reaction (4%; includes burning sensation at injection site, erythema at injection site, injection site pain)
Nervous system: Agitation (oral: ≤6%), anxiety (oral: ≤6%), dizziness (7%), drowsiness (IV: ≤8%), paresthesia (IV: 2%), sedated state (IV: ≤8%), sensation of cold (IV: 2%)
Respiratory: Bronchospasm (<2%), hypoxia (oral: 9%)
Miscellaneous: Fever (2% to 8%)
<1%:
Cardiovascular: Hypotension
Nervous system: Extrapyramidal reaction (Ritter 2003; Sprung 2003)
Frequency not defined:
Cardiovascular: Angina pectoris, peripheral vascular disease, tachycardia
Endocrine & metabolic: Hypokalemia
Nervous system: Tonic clonic epilepsy
Postmarketing:
Cardiovascular: Atrial fibrillation (Havrilla 2009), bradycardia (Afonso 2009; Rapp 2015), depression of ST segment on ECG, flushing, ischemic heart disease (most commonly due to coronary artery spasm and may occur with oral or IV [predominantly IV]; occurred immediately after IV administration and resolved with treatment), palpitations, prolonged QT interval on ECG (Ganjare 2013; Moffett 2016), second degree atrioventricular block, supraventricular tachycardia, syncope, torsades de pointes (Lee 2017; Patel 2019), ventricular premature contractions, ventricular tachycardia
Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis (Saraogi 2012), urticaria (Bousquet 2005)
Gastrointestinal: Hiccups, intestinal obstruction (Cohen 2014)
Hematologic & oncologic: Positive lymphocyte transformation test
Hepatic: Hepatic failure
Hypersensitivity: Angioedema, fixed drug eruption (Maitra 2017), hypersensitivity reaction (Garcia Nunez 2015; Leung 2013), nonimmune anaphylaxis
Nervous system: Dystonic reaction (Diaz-Parlet 2015), serotonin syndrome (George 2008)
Neuromuscular & skeletal: Laryngospasm
Ophthalmic: Accommodation disturbance, oculogyric crisis (Macachor 2014), transient blindness (lasted ≤48 hours) (Cherian 2005), transient blurred vision (following infusion)
Respiratory: Dyspnea, laryngeal edema, stridor
Hypersensitivity to ondansetron or any component of the formulation; concomitant use with apomorphine
Concerns related to adverse effects:
• Serotonin syndrome: Serotonin syndrome (SS) has been reported with 5-HT3 receptor antagonists, predominantly when used in combination with other serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and/or methylene blue). Some of the cases have been fatal. The majority of serotonin syndrome reports due to 5-HT3 receptor antagonist have occurred in a postanesthesia setting or in an infusion center. SS has also been reported following overdose of ondansetron. Signs/symptoms of SS include mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile BP, diaphoresis, dizziness, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Phenylalanine: Orally disintegrating tablets contain phenylalanine.
Other warnings/precautions:
• Chemotherapy-associated emesis: Antiemetics are most effective when used prophylactically (MASCC/ESMO [Roila 2016]). If emesis occurs despite optimal antiemetic prophylaxis, re-evaluate emetic risk, disease status, concurrent morbidities and current medications to assure antiemetic regimen is optimized (ASCO [Hesketh 2020]).
Zuplenz has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Film, Oral:
Zuplenz: 4 mg (30 ea [DSC]); 8 mg (30 ea [DSC])
Solution, Injection, as hydrochloride [strength expressed as base]:
Generic: 4 mg/2 mL (2 mL); 40 mg/20 mL (20 mL)
Solution, Injection, as hydrochloride [strength expressed as base, preservative free]:
Generic: 4 mg/2 mL (2 mL)
Solution, Oral, as hydrochloride [strength expressed as base]:
Generic: 4 mg/5 mL (5 mL, 50 mL)
Solution Prefilled Syringe, Injection, as hydrochloride:
Generic: 4 mg/2 mL (2 mL)
Tablet, Oral, as hydrochloride [strength expressed as base]:
Zofran: 4 mg, 8 mg [DSC]
Generic: 4 mg, 8 mg, 24 mg
Tablet Disintegrating, Oral:
Generic: 4 mg, 8 mg
May be product dependent
Solution (Ondansetron HCl Injection)
4 mg/2 mL (per mL): $0.28 - $1.35
40 mg/20 mL (per mL): $0.30 - $1.25
Solution (Ondansetron HCl Oral)
4 mg/5 mL (per mL): $4.78 - $6.00
Solution Prefilled Syringe (Ondansetron HCl Injection)
4 mg/2 mL (per mL): $1.11
Tablet, orally-disintegrating (Ondansetron Oral)
4 mg (per each): $22.25 - $23.11
8 mg (per each): $36.66 - $38.50
Tablets (Ondansetron HCl Oral)
4 mg (per each): $0.54 - $24.89
8 mg (per each): $0.64 - $41.53
24 mg (per each): $106.51
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Film, Oral:
Ondissolve ODF: 4 mg (6 ea, 10 ea, 50 ea); 8 mg (6 ea, 10 ea, 50 ea) [contains levomenthol, polyethylene glycol (macrogol), polysorbate 80]
Solution, Intravenous:
Zofran: 2 mg/mL ([DSC])
Generic: 2 mg/mL (2 mL, 4 mL, 5 mL, 20 mL)
Solution, Oral, as hydrochloride [strength expressed as base]:
Zofran: 4 mg/5 mL ([DSC]) [contains alcohol, usp, sodium benzoate]
Generic: 4 mg/5 mL (50 mL)
Tablet, Oral, as hydrochloride [strength expressed as base]:
Zofran: 4 mg [DSC], 8 mg [DSC]
Generic: 4 mg, 8 mg
Tablet Disintegrating, Oral:
Zofran ODT: 4 mg, 8 mg [contains aspartame, methylparaben sodium, propylparaben sodium]
Generic: 4 mg, 8 mg
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).
Oral: May administer without regard to meals. For chemotherapy-induced nausea and vomiting, administer 30 minutes prior to chemotherapy.
Dosage-form specific:
Orally disintegrating tablet (Zofran ODT): Do not remove from blister until needed. Peel backing off the blister; do not push tablet through foil backing. Using dry hands, place tablet on tongue and allow to dissolve; swallow with saliva (no need to administer with liquids).
Oral solution: Measure with a calibrated measuring device.
Parenteral:
IV:
Intermittent infusion:
Chemotherapy-induced nausea and vomiting: Infuse over 15 minutes.
Cyclic vomiting syndrome: Infuse over 15 to 30 minutes (Ref).
IV push: Gastroenteritis, postoperative nausea/vomiting (PONV): May be administered undiluted IV over 2 to 5 minutes (Ref).
IM: Adolescents: PONV: Administer as undiluted injection.
Oral: Oral dosage forms should be administered 30 minutes prior to chemotherapy; 1 to 2 hours before radiation; 30 to 60 minutes prior to surgery or induction of anesthesia
Orally disintegrating tablets: Do not remove from blister until needed. Peel backing off the blister, do not attempt to push tablet through the foil. Using dry hands, place tablet on tongue and allow to dissolve. Swallow with saliva (no need to administer with liquids).
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 to 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.
IM: Should be administered undiluted.
IV:
IVPB: Infuse diluted solution over 15 minutes
Chemotherapy-induced nausea and vomiting: Give first dose 30 minutes prior to beginning chemotherapy.
IV push: Prevention of postoperative nausea and vomiting: Single doses may be administered IV injection as undiluted solution over at least 30 seconds but preferably over 2 to 5 minutes
Oral disintegrating tablet: Store between 2°C and 30°C (36°F and 86°F).
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 upright in carton between 15°C and 30°C (59°F and 86°F). Protect from light.
Tablet: Store between 2°C and 30°C (36°F and 86°F). Protect from light.
Vial: Store between 2°C and 30°C (36°F and 86°F). Protect from light. Chemically and physically stable when mixed in D5W or NS for 48 hours at room temperature; however, diluents generally do not contain a preservative and sterile precautions should be observed. After dilution, do not use beyond 24 hours.
Premixed bag in D5W: Store at 20°C to 25°C (68°F to 77°F), excursions permitted from 15°C to 30°C (59°F to 86°F); may refrigerate; avoid freezing and excessive heat; protect from light.
Oral:
Orally disintegrating tablets, oral solution, oral tablets: Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy (FDA approved in ages ≥4 years and adults); prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy (including cisplatin) (FDA approved in adults); prevention of nausea and vomiting associated with radiotherapy (FDA approved in adults); prevention of postoperative nausea and vomiting (FDA approved in adults).
Soluble Film (Zuplenz): Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy (FDA approved in ages ≥4 years and adults); prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy or radiotherapy (FDA approved in adults); prevention of postoperative nausea and vomiting (PONV) (FDA approved in adults).
Parenteral: Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy (including high-dose cisplatin) (FDA approved in ages ≥6 months and adults); prevention of postoperative nausea and vomiting (FDA approved in ages ≥1 month and adults); has also been used in the treatment of acute gastroenteritis and cyclic vomiting syndrome.
Ondansetron may be confused with dolasetron, granisetron, palonosetron
Zofran may be confused with Zantac, Zosyn
Substrate of CYP1A2 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amiodarone: May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the QTc-prolonging effect of Ondansetron. Risk C: Monitor therapy
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Ondansetron. Risk C: Monitor therapy
Dabrafenib: Ondansetron may enhance the QTc-prolonging effect of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Domperidone: May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Fluorouracil Products: Ondansetron may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Haloperidol: Ondansetron may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
MetFORMIN: Ondansetron may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Panobinostat: Ondansetron may enhance the arrhythmogenic effect of Panobinostat. Risk C: Monitor therapy
Pentamidine (Systemic): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of Ondansetron. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Ondansetron may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation or serotonin syndrome may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation, ventricular arrhythmias, including torsades de pointes, when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-Prolonging Inhalational Anesthetics (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Serotonergic Agents (High Risk): Ondansetron may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Tapentadol: Ondansetron may diminish the analgesic effect of Tapentadol. Risk C: Monitor therapy
TraMADol: Ondansetron may enhance the serotonergic effect of TraMADol. This could result in serotonin syndrome. Ondansetron may diminish the therapeutic effect of TraMADol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and diminished tramadol efficacy when these agents are combined. Risk C: Monitor therapy
Tablet: Food slightly increases the extent of absorption. Management: Administer without regard to meals.
Some products may contain phenylalanine.
Ondansetron crosses the placenta (Elkomy 2014; Siu 2006).
Ondansetron can be detected in fetal tissue (Siu 2006). The risk of developing a major congenital malformation following first trimester exposure is under study. Risks related to specific birth defects (eg, cardiac anomalies, oral clefts) requires confirmation; available human data are conflicting (ACOG 2018; Dormuth 2021; Kaplan 2019; Lemon 2020; Lavecchia 2018; Picot 2020). Clearance is decreased immediately after birth in neonates exposed to ondansetron in utero (Elkomy 2014).
Due to pregnancy-induced physiologic changes, clearance of ondansetron may increase as pregnancy progresses (Lemon 2016). Dose adjustment is not needed when administered for the prevention of nausea and vomiting associated with cesarean delivery (Elkomy 2014).
Ondansetron may be considered for the treatment of severe or refractory nausea and vomiting of pregnancy (NVP) when preferred agents have failed (ACOG 2018; Campbell 2016). Until additional information related to fetal safety is available, current guidelines suggest use prior to 10 weeks gestation be individualized (ACOG 2018). Dose-dependent QT-interval prolongation can occur with use; therefore, ECG monitoring is recommended in patients with risk factors for arrhythmia (ACOG 2018); this may include patients with electrolyte abnormalities associated with some cases of NVP (Koren 2012).
Ondansetron may be considered as part of a multimodal approach to prevent nausea and vomiting associated with cesarean delivery. A combination of ≥2 antiemetics with different mechanisms of action is recommended to treat intraoperative and postoperative nausea and vomiting (Bollag 2021; Griffiths 2012; Habib 2013; Jetling 2017; Macones 2019; Zhou 2018).
An international consensus panel recommends that 5-HT3 antagonists (including ondansetron) can be used when necessary in pregnant patients receiving chemotherapy for the treatment of gynecologic cancers (Amant 2019).
ECG if applicable (eg, high-risk or elderly patients, concurrent use of other medications known to prolong QT interval, electrolyte abnormalities [hypokalemia or hypomagnesemia], heart failure, bradyarrhythmias, and cumulative high-dose anthracycline therapy); serum potassium and magnesium levels. Monitor for signs/symptoms of serotonin syndrome and hypersensitivity; monitor for decreased bowel activity (particularly in patients at risk for bowel obstruction). Monitor for signs/symptoms of myocardial ischemia.
Ondansetron is a selective 5-HT3-receptor antagonist which blocks serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone
Onset of action: ~30 minutes
Absorption: Oral: 100%; nonlinear absorption occurs with increasing oral doses; Zofran ODT tablets are bioequivalent to Zofran tablets; absorption does not occur via oral mucosa
Distribution: Vd:
Infants and Children: Surgical patients:
1 to 4 months: 3.5 L/kg
5 to 24 months: 2.3 L/kg
3 to 12 years: 1.65 L/kg
Children and Adolescents: Cancer patients: 4 to 18 years: 1.9 L/kg
Adults: 1.9 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: 50% to 70% due to some first-pass metabolism; in cancer patients (adults), 85% to 87% bioavailability possibly related to changes in metabolism
Half-life elimination:
Children: Cancer patients: Children and Adolescents: 4 to 18 years: 2.8 hours; Surgical patients: Infants 1 to 4 months: 6.7 hours; Infants and Children 5 months to 12 years: 2.9 hours
Adults: 3 to 6 hours; Mild-to-moderate hepatic impairment (Child-Pugh classes A and B): 12 hours; Severe hepatic impairment (Child-Pugh class C): 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%)
Clearance:
Cancer patients: Children and Adolescents 4 to 18 years: 0.599 L/kg/hour
Surgical patients: Infants and Children: 1 to 4 months: 0.401 L/kg/hour; 5 to 24 months: 0.581 L/kg/hour; 3 to 12 years: 0.439 L/kg/hour
Adult (normal): 19 to 40 years: 0.381 L/kg/hour; 61 to 74 years: 0.319 L/kg/hour; >75 years: 0.262 L/kg/hour
Altered kidney function: Mean plasma clearance is reduced by 41% (IV) and 50% (oral) in patients with severe renal impairment (CrCl <30 mL/minute).
Hepatic function impairment: In patients with mild to moderate impairment, clearance is reduced 2-fold and the mean half-life is increased to 11.6 hours (compared to 5.7 hours in subjects with normal hepatic function). Clearance is reduced 2- to 3-fold and the apparent Vd is increased, and the half-life is increased to 20 hours in patients with severe hepatic impairment (Child-Pugh class C).
Older adult: In elderly patients >75 years of age, there is a reduction in clearance and an increase in elimination half-life.
Sex: The extent and rate of absorption is greater in women than in men. There is slower clearance, a smaller volume of distribution, and higher bioavailability in women.
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