Professional Information

Ondansetron (Systemic)

VA CLASSIFICATION
Primary: GA605

Commonly used brand name(s): Zofran; Zofran ODT.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Category:

Antiemetic. ^{01}—

Indications

Accepted

Nausea and vomiting, cancer chemotherapy–induced (prophylaxis)—Ondansetron is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of moderately or highly emetogenic cancer chemotherapy ^{01} ^{08} ^{09} ^{22} ^{23} ^{37} ^{53} ^{55} ^{62}, including high-dose cisplatin. ^{01} ^{08} ^{23}
—Studies done to date comparing ondansetron to high-dose metoclopramide have shown ondansetron to be more effective in preventing nausea and vomiting induced by emetogenic chemotherapy agents during the acute phase lasting 24 hours after the start of chemotherapy. ^{03} ^{05} ^{07} ^{13} ^{14} ^{37} ^{39} ^{40} ^{41} ^{42} ^{55} ^{56}
—The combination of ondansetron plus dexamethasone has been shown to provide better emetic control over cisplatin-induced emesis than ondansetron alone. ^{37} ^{44} ^{45} ^{46}

Nausea and vomiting, postoperative (prophylaxis and treatment)—Ondansetron is indicated for the prevention and treatment of postoperative nausea and vomiting. ^{22} ^{23} ^{37} ^{47} ^{50} ^{52} ^{62} ^{67} Patients at greatest risk of developing postoperative nausea and vomiting include patients who have previously experienced postoperative nausea, patients predisposed to motion sickness, and patients with high levels of preoperative anxiety. ^{47} The incidence of postoperative nausea and vomiting is also higher in women ^{47} ^{49} ^{50} and children ^{47} than in men and adults, respectively. Routine prophylaxis is not recommended for patients in whom there is little expectation that postoperative nausea and vomiting will occur, except in cases in which the stress of vomiting may damage the operation site. ^{23} ^{37} ^{47}

Nausea and vomiting, radiotherapy-induced (prophylaxis)—Ondansetron tablets are indicated for the prevention of nausea and vomiting associated with radiotherapy ^{22} ^{37} ^{57} ^{62} ^{69} in patients receiving total body irradiation ^{57} ^{60} ^{62}, or single high-dose fraction or daily fractions to the abdomen. ^{57} ^{62} ^{67} ^{69} ^{70}

Unaccepted
Ondansetron is not effective in preventing motion-induced nausea and vomiting. ^{22}

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
293.4 (ODT orally disintegrating tablets) and 365.9 (oral tablets and solution).^{72}

pH
Injection: 3.3 to 4 ^{23} ^{33} ^{36} ^{67}.

Mechanism of action/Effect:

Antiemetic—Ondansetron is a competitive ^{05} ^{11}, highly ^{03} ^{11} selective ^{01} ^{04} ^{05} ^{06} ^{07} ^{08} ^{09} ^{10} ^{11} ^{12} ^{22} ^{23} ^{25} ^{33} ^{37} antagonist of 5-hydroxytryptamine (serotonin) subtype 3 (5-HT ₃) receptors. ^{01} ^{04} ^{05} ^{06} ^{07} ^{08} ^{09} ^{10} ^{11} ^{12} ^{13} ^{14} ^{22} ^{33} ^{38} 5-HT ₃ receptors are present peripherally ^{01} ^{04} ^{11} ^{12} ^{13} ^{23} ^{25} on vagal nerve terminals ^{01} ^{04} ^{11} ^{12} ^{23} ^{25} ^{38} and centrally ^{01} ^{04} ^{10} ^{11} ^{12} ^{13} ^{23} ^{25} in the area postrema of the brain. ^{01} ^{04} ^{05} ^{10} ^{11} ^{12} ^{23} ^{25} ^{38} It is not certain whether ondansetron's action is mediated peripherally, centrally, or both. ^{01} ^{04} ^{22} ^{23} ^{25} Cytotoxic drugs and radiation appear to damage gastrointestinal mucosa, causing the release of serotonin from the enterochromaffin cells of the gastrointestinal tract. Stimulation of 5-HT ₃ receptors causes transmission of sensory signals to the vomiting center via vagal afferent fibers to induce vomiting. ^{23} ^{25} ^{26} ^{37} ^{38} ^{39} By binding to 5-HT ₃ receptors, ondansetron blocks vomiting mediated by serotonin release. ^{26} ^{37} ^{38} ^{39}

Ondansetron has no dopamine-receptor antagonist activity. ^{01} ^{03} ^{04} ^{05} ^{07} ^{08} ^{09} ^{10} ^{11} ^{14} ^{23} ^{25} ^{33} ^{43}

Other actions/effects:

Multiple oral doses or multiday intravenous doses of ondansetron administered to healthy volunteers slowed colonic transit time. ^{01} ^{06} ^{12} ^{23} ^{25} ^{37} ^{52} However, following single intravenous doses of 0.15 mg of ondansetron per kg of body weight (mg/kg), no effects were observed on esophageal motility ^{01} ^{23} ^{25}, gastric motility ^{01} ^{23} ^{25}, lower esophageal sphincter pressure ^{01} ^{23} ^{25}, small intestine transit time ^{01} ^{12} ^{23} ^{25} ^{26} ^{37} ^{52}, or plasma prolactin concentrations. ^{01} ^{23} ^{25}

Absorption:

Ondansetron is well absorbed after oral administration and undergoes limited first-pass metabolism. The extent and rate of ondansetron's absorption following a single oral dose is greater in women than in men. ^{25} ^{32} However, it is not known if this difference is clinically significant. ^{25} Mean bioavailability, in healthy subjects, following a single 8-mg oral dose is approximately 56%.^{72}

Distribution:

The volume of distribution (Vol _D) in healthy young males following administration of 8 mg of ondansetron as an intravenous infusion over 5 minutes was about 160 L. ^{16} ^{37} Patients 4 to 12 years of age reportedly have a Vol _D somewhat larger than do adults. ^{01} ^{23}

Thirty-six percent ^{19} of circulating ondansetron is distributed into erythrocytes. ^{01} ^{19} ^{23} ^{25}

Protein binding:

High (70 to 76%). ^{01} ^{16} ^{22} ^{23} ^{25} ^{26} ^{37} ^{39}

Biotransformation:

Hepatic; extensive. ^{01} ^{22} ^{23} ^{25} ^{26} ^{32} ^{37} Primarily hydroxylation, followed by glucuronide or sulfate conjugation. ^{01} ^{17} ^{22} ^{23} ^{25} ^{26} ^{37}

Half-life:

The mean elimination half-life in adult cancer patients is 5.7 hours. ^{01} ^{22} ^{23} ^{55}^{72} Elderly patients ^{01} ^{12} ^{26} ^{39} tend to have an increased elimination half-life, while most pediatric patients less than 15 years of age have shorter mean terminal half-lives (range, 2.5 to 3 hours) than patients older than 15 years of age. ^{01} ^{23} ^{26} Adults with mild to moderate hepatic impairment had a mean half-life of 11.6 hours^{72}, while those with severe hepatic impairment had a mean half-life prolonged to 20.6 hours ^{67}.

A study performed in normal volunteers to evaluate the pharmacokinetics of a single 4-mg dose of ondansetron administered as a 5-minute intravenous infusion and as a single intramuscular injection showed that the mean elimination half-life was not affected by route of administration. ^{67}

Peak plasma concentration

Following administration of a single intravenous dose of 0.15 mg/kg to healthy volunteers, peak plasma concentrations of 102 to 106 nanograms per mL were observed in those from 19 to 74 years of age, and 170 nanograms per mL in those ³ 75 years of age. ^{67} Mean peak plasma concentrations in volunteers who received a single 4-mg dose of ondansetron via a 5-minute intravenous infusion or as a single intramuscular injection were 42.9 nanograms/mL at 10 minutes following the infusion, and 31.9 nanograms/mL at 41 minutes after intramuscular injection. ^{67}

Following administration of a single oral dose of 8 mg of ondansetron to healthy volunteers: ^{25}

Age group (years)	Gender	Peak plasma concentration (nanograms per mL)
19–40	M	26.2
	F	42.7
61–74	M	24.1
	F	52.4
³75	M	37
	F	46.1

The higher plasma concentrations in females may be attributed to slower clearance, smaller apparent Vol _D (adjusted for weight), and higher absolute bioavailability in females than in males. ^{25} ^{32}

Elimination:
    Predominantly hepatic ^{58}; less than 5% of an intravenous dose of ondansetron is recovered unchanged in the urine. ^{01} ^{16} ^{17} ^{23} ^{25} ^{32} ^{37} ^{39}
    Following administration of a single intravenous dose of 0.15 mg/kg to healthy volunteers, plasma clearance values were 0.381 liters per hour per kg of body weight (L/hr/kg) in subjects 9 to 40 years of age, 0.319 L/hr/kg in subjects 61 to 74 years of age, and 0.262 L/hr/kg in subjects ³ 75 years of age. ^{01} ^{32} ^{67}
    Elderly patients tended to have lower clearance values than did younger adults ^{01} ^{12} ^{23} ^{37}, while most pediatric patients 4 to 12 years of age had greater clearance values than adults. ^{01} ^{23}

Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to granisetron or dolasetron may also be sensitive to ondansetron. ^{24} ^{70}

Carcinogenicity

Carcinogenic effects were not seen in 2-year studies ^{39} in rats and mice given ondansetron orally in doses up to 10 and 30 mg per kg of body weight (mg/kg) per day, respectively. ^{01} ^{23} ^{25}

Mutagenicity

Standard tests showed no mutagenic activity of ondansetron. ^{01} ^{23} ^{25} ^{39}

Pregnancy/Reproduction
Fertility—
Ondansetron had no effect on the fertility or reproductive performance of male and female rats when given in oral doses up to 15 mg/kg per day. ^{23} ^{25}

Pregnancy—
Adequate and well-controlled studies in humans have not been done. ^{01} ^{22} ^{23} ^{25}

Studies in pregnant rats and rabbits given intravenous doses of up to 4 mg/kg per day ^{01} ^{23}, and oral doses of up to 15 and 30 mg/kg per day, respectively, ^{25} have not shown that ondansetron causes adverse effects in the fetus.

FDA Pregnancy Category B. ^{01} ^{23} ^{25} ^{26}

Breast-feeding

It is not known whether ondansetron is distributed into human breast milk. However, ondansetron is distributed into the milk of rats. ^{01} ^{22} ^{23} ^{25}

Pediatrics

Studies performed to date that included cancer patients 4 to 18 years of age and postoperative patients 2 to 12 years of age have not demonstrated pediatrics-specific problems that would limit the usefulness of ondansetron in children. ^{01} ^{23} ^{25} ^{52} ^{67}

Geriatrics

Studies performed to date that included cancer patients over 65 years of age have not demonstrated geriatrics-specific problems that would limit the usefulness of ondansetron in the elderly. ^{01} ^{23} ^{25}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Enzyme inducers, hepatic, cytochrome P450 (see Appendix II ) or
Enzyme inhibitors, hepatic, various (see Appendix II )    (because ondansetron is metabolized by hepatic cytochrome P450 enzymes, inducers or inhibitors of these enzymes potentially may alter its clearance and half-life; ondansetron does not appear to induce or inhibit the cytochrome P450 enzyme system of the liver ^{01} ^{21} ^{23} ^{25})

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT])^{01}^{05}^{08}^{12}^{14}^{15}^{22}^{23}^{25}^{26}^{47} and
Aspartate aminotransferase (AST [SGOT])^{01}^{05}^{08}^{12}^{14}^{15}^{22}^{23}^{25}^{26}    (values may be increased; increases reportedly are transient and unrelated to dose or duration of therapy ^{01} ^{22} ^{23} ^{25})

Bilirubin, serum^{05}^{08}^{15}^{26}    (concentrations may be increased; increases reportedly are transient and unrelated to dose or duration of therapy ^{01})

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Risk-benefit should be considered when the following medical problems exist
Hepatic function impairment^{07}^{21}^{71}    (use of ondansetron may result in increases in hepatic enzymes; in patients with severe hepatic insufficiency, ondansetron clearance is reduced, plasma half-life is increased, and bioavailability approaches 100%; dosage adjustments are needed)

Phenylketonuria (PKU)    (Zofran brand of ondansetron oral disintegrating tablets contains aspartame, which is metabolized to phenylalanine ^{71})

Surgery, abdominal^{23}    (use of ondansetron may mask a progressive ileus and/or gastric distension)

Sensitivity to ondansetron^{22}^{23}^{25} , granisetron^{24} , or dolasetron

Side/Adverse Effects

Note: Since ondansetron is used in conjunction with cancer chemotherapeutic agents, it is difficult to attribute some side effects, such as diarrhea and fever, to ondansetron alone. ^{20}
Signs and symptoms consistent with extrapyramidal effects have been reported in a very small number of patients receiving ondansetron ^{27} ^{28} ^{29} ^{37}; however, a causal relationship has not been established. ^{22} ^{23} ^{25}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare

Anaphylaxis^{22}^{23}^{25}^{26}^{30} (hypotension; skin rash, hives, and/or itching; troubled breathing)

bronchospasm^{01}^{22}^{23}^{25}^{30} (shortness of breath, tightness in chest, troubled breathing, or wheezing)

chest pain^{22}^{23}^{31}

injection-site reactions^{67} (pain, redness, and burning at site of injection)

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent

Constipation^{01}^{03}^{06}^{12}^{13}^{15}^{22}^{23}^{25}^{26}^{32}^{37}^{39}^{53}

diarrhea^{01}^{03}^{04}^{05}^{07}^{08}^{09}^{10}^{13}^{14}^{15}^{23}^{32}^{55}

fever^{02}^{08}^{10}^{23}^{55}

headache^{01}^{02}^{03}^{04}^{05}^{07}^{08}^{09}^{10}^{12}^{13}^{14}^{15}^{22}^{23}^{25}^{26}^{32}^{37}^{39}^{47}^{53}^{55}

Incidence less frequent or rare

Abdominal pain or stomach cramps^{08}^{12}^{15}^{25}^{26}

cold sensation^{67} (feeling cold)

dizziness or lightheadedness^{10}^{12}^{26}^{37}^{47}

drowsiness^{03}^{05}^{10}^{14}^{15}^{32}^{37}^{47}

dryness of mouth^{03}^{10}^{13}^{14}^{25}^{37}

paresthesias^{67} (burning, tingling, or prickling sensations)

pruritus^{67} (itching)

skin rash^{01}^{22}^{23}^{25}

unusual tiredness or weakness^{03}^{08}^{13}^{25}

Overdose
For information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
Individual doses as large as 145 mg and total daily dosages as large as 252 mg have been administered intravenously without significant adverse events. ^{67}

Hypotension and faintness occurred in a patient who ingested 48 mg of oral ondansetron. Sudden blindness (amaurosis) of 2 to 3 minutes' duration plus severe constipation occurred in another patient who was administered a single dose of 72 mg of ondansetron intravenously. A vasovagal episode with transient second-degree heart block was observed in another patient following the infusion of 32 mg of ondansetron over a 4-minute period. In all cases, the events resolved completely. ^{67}

Treatment of overdose
There is no specific antidote for ondansetron overdose ^{67}.

Supportive care—Patients should be managed with appropriate supportive therapy. ^{67} Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric evaluation.

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ondansetron (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to ondansetron, granisetron, or dolasetron

Proper use of this medication
Taking additional dose if vomiting occurs within 30 minutes after a dose; checking with doctor if vomiting persists ^{58}

Proper handling/administration of the oral disintegrating tablets ^{71}

» Proper dosing
Missed dose: Taking missed dose as soon as possible if nausea or vomiting occurs ^{22} ^{59}

» Proper storage

Side/adverse effects
Signs of potential side effects, especially anaphylaxis, bronchospasm, chest pain, or injection-site reactions

General Dosing Information
For prophylaxis against nausea and vomiting induced by highly emetogenic chemotherapeutic agents, the parenteral form of ondansetron is recommended. ^{23} The oral forms of ondansetron are indicated for the prevention of nausea and vomiting induced by moderately emetogenic-chemotherapeutic agents ^{25}.

Zofran brand of oral disintegrating tablets is a freeze-dried formulation of ondansetron that rapidly disintegrates on the tongue and does not require water to aid dissolution or swallowing. ^{71}

Oral disintegrating tablets may contain aspartame, which is metabolized to phenylalanine. This substance must be used with caution in patients with phenylketonuria.

Oral Dosage Forms

ONDANSETRON HYDROCHLORIDE ORAL SOLUTION

Usual adult and adolescent dose
Nausea and vomiting, cancer chemotherapy–induced (prophylaxis)
Initial: Oral, 8 mg thirty minutes prior to chemotherapy. ^{25}

Post-chemotherapy: Oral, 8 mg eight hours after the initial dose, followed by 8 mg every twelve hours for one to two days. ^{62} ^{64} ^{65}

Nausea and vomiting, postoperative (prophylaxis)
Oral, 16 mg one hour prior to induction of anesthesia. ^{62} ^{63} ^{64}

Nausea and vomiting, radiotherapy-induced (prophylaxis)
Initial: Oral, 8 mg one to two hours prior to radiotherapy. ^{22} ^{57}

Post-radiotherapy: Oral, 8 mg every eight hours ^{22} ^{57} ^{67} ^{69} ^{70}.

Note: In patients with hepatic function impairment, the maximum recommended dose of ondansetron is 8 mg a day. ^{22} ^{25} ^{37}

Usual pediatric dose
Nausea and vomiting, cancer chemotherapy–induced (prophylaxis)

Children up to 4 years of age:
Dosage has not been established.

Children 4 to 12 years of age:
Initial—Oral, 4 mg thirty minutes prior to chemotherapy. ^{22} ^{25}

Post-chemotherapy—Oral, 4 mg four and eight hours after the initial dose ^{22} ^{25}, followed by 4 mg every eight hours for one to two days. ^{62}

Children 12 years of age and older:
See Usual adult and adolescent dose. ^{25}

Nausea and vomiting, postoperative (prophylaxis) ^{62} or
Nausea and vomiting, radiotherapy-induced (prophylaxis) ^{22} ^{57} ^{64}
Dosage has not been established.

Usual geriatric dose
See Usual adult and adolescent dose. ^{22} ^{25} ^{57} ^{62}

Strength(s) usually available
U.S.—

4 mg per 5 mL (Rx) [Zofran (strawberry flavored) (sorbitol) (citric acid anhydrous) (sodium benzoate) (sodium citrate)]

Canada—

4 mg per 5 mL (Rx) [Zofran (strawberry flavored) (sorbitol) (citric acid anhydrous) (sodium benzoate) (sodium citrate dihydrate )]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Store bottles upright in cartons ^{70}.

ONDANSETRON HYDROCHLORIDE TABLETS

Usual adult and adolescent dose
See Ondansetron Hydrochloride Oral Solution .

Usual pediatric dose
See Ondansetron Hydrochloride Oral Solution .

Usual geriatric dose
See Ondansetron Hydrochloride Oral Solution .

Strength(s) usually available
U.S.—

4 mg (Rx) [Zofran (lactose) (microcrystalline cellulose) (pregelatinized starch) (hydroxypropyl methylcellulose) (magnesium stearate) (titanium dioxide) ( sodium benzoate)]

8 mg (Rx) [Zofran (lactose) (microcrystalline cellulose) (pregelatinized starch) (hydroxypropyl methylcellulose) (magnesium stearate) (titanium dioxide) ( iron oxide)]

Canada—

4 mg (Rx) [Zofran (lactose) (microcrystalline cellulose) (pregelatinized starch) (magnesium stearate) (methyl hydroxypropyl cellulose) (Opadry yellow) ( Opaspray yellow [containing titanium dioxide and iron oxide yellow])]

8 mg (Rx) [Zofran (lactose) (microcrystalline cellulose) (pregelatinized starch) (magnesium stearate) (methyl hydroxypropyl cellulose) (Opadry yellow) ( Opaspray yellow [containing titanium dioxide and iron oxide yellow])]

Packaging and storage:
Store between 2 and 30 °C (36 and 86 °F), unless otherwise specified by manufacturer. Protect from light. ^{25}

ONDANSETRON ORAL DISINTEGRATING TABLETS

Note: Zofran brand of oral disintegrating tablets is a freeze-dried formulation of ondansetron which rapidly disintegrates on the tongue and does not require water to aid dissolution or swallowing. ^{71}

Usual adult and adolescent dose
See Ondansetron Hydrochloride Oral Solution . ^{71}

Usual pediatric dose
See Ondansetron Hydrochloride Oral Solution . ^{71}

Usual geriatric dose
See Ondansetron Hydrochloride Oral Solution . ^{71}

Strength(s) usually available
U.S.—

4 mg (Rx) [Zofran ODT (aspartame [< 0.03 mg] ) (gelatin) (mannitol ) (methylparaben sodium) ( propylparaben sodium) (strawberry flavor)]

8 mg (Rx) [Zofran (aspartame [< 0.03 mg]) (gelatin) (mannitol) (methylparaben sodium) (propylparaben sodium) (strawberry flavor)]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 30 °C (36 and 86 °F), unless otherwise specified by manufacturer. Protect from light. ^{71}

Caution:
Zofran brand of oral disintegrating tablets contains aspartame, which is metabolized to phenylalanine and must be used with caution in patients with phenylketonuria.

Additional information:
Proper handling/administration—With dry hands, peel back the foil backing of one blister. Do not attempt to push the oral disintegrating tablet through the foil backing. Gently remove the tablet and place it immediately on top of the tongue. It will dissolve in seconds, and should then be swallowed with saliva. ^{71}

Parenteral Dosage Forms

ONDANSETRON INJECTION USP

Usual adult dose
Nausea and vomiting, cancer chemotherapy–induced (prophylaxis)
Intravenous, 32 mg administered over fifteen minutes beginning thirty minutes prior to chemotherapy. ^{22} ^{23} ^{55} ^{56} ^{66} Alternatively, three doses of 150 mcg (0.15 mg) per kg of body weight, each administered over fifteen minutes, with the initial dose beginning thirty minutes prior to chemotherapy, and subsequent doses administered four and eight hours after the first dose. ^{01} ^{22} ^{23} ^{55} ^{56} Or, 8 mg administered over fifteen minutes beginning thirty minutes prior to chemotherapy, followed immediately by a continuous infusion of 1 mg per hour for up to twenty-four hours. ^{22}

Nausea and vomiting, postoperative (prophylaxis)
Intravenous, 4 mg administered over not less than thirty seconds and preferably over two to five minutes, beginning immediately prior to induction of anesthesia. ^{22} ^{23} ^{49} ^{50} Alternatively, 4 mg may be administered undiluted as a single intramuscular injection ^{67}.

Nausea and vomiting, postoperative (treatment)
Intravenous, 4 mg administered over not less than thirty seconds and preferably over two to five minutes ^{22} ^{33} ^{51}, given postoperatively if nausea or vomiting occurs. Alternatively, 4 mg may be administered undiluted as a single intramuscular injection ^{67}.

Note: In patients with severe hepatic function impairment, the maximum recommended dose of ondansetron is 8 mg a day, infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. ^{19} ^{22} ^{23} ^{37} ^{67}

Usual pediatric dose
Nausea and vomiting, cancer chemotherapy–induced (prophylaxis)
Children up to 4 years of age: Dosage has not been established. ^{01}

Children 4 to 18 years of age: Intravenous, three doses of 150 mcg (0.15 mg) per kg of body weight, each administered over fifteen minutes, with the initial dose beginning thirty minutes prior to chemotherapy, and subsequent doses administered four and eight hours after the first dose. ^{01} ^{23} Alternatively, 3 to 5 mg per square meter of body surface area administered over fifteen minutes beginning immediately prior to chemotherapy, ^{22} ^{37} followed after therapy by oral ondansetron 4 mg every eight hours for up to five days. ^{22}

Nausea and vomiting, postoperative
Children up to 2 years of age: Dosage has not been established. ^{01} ^{67}

Children 2 to 12 years of age: Intravenous, a single dose of 150 mcg (0.15 mg) per kg of body weight for those weighing 40 kg or less, or a single 4-mg dose for those weighing more than 40 kg, administered over not less than thirty seconds and preferably over two to five minutes. ^{67}

Usual geriatric dose
See Usual adult dose . ^{22} ^{23}

Strength(s) usually available
U.S.—

2 mg per mL (Rx) [Zofran (sodium chloride) (citric acid monohydrate 0.5 mg) ( sodium citrate dihydrate 0.25 mg) ([may contain methylparaben 1.2 mg, propylparaben 0.15 mg])]

32 mg per 50 mL (premixed) (Rx) [Zofran (dextrose 2500 mg ) (citric acid 26 mg) ( sodium citrate 11.5 mg)]

Canada—

2 mg per mL (Rx) [Zofran]

Packaging and storage:
Store between 2 and 30 °C (36 and 86 °F), unless otherwise specified by manufacturer. Protect from light. ^{01} ^{22} ^{23} Do not freeze. ^{69}

Preparation of dosage form:
For intravenous administration—The manufacturer recommends that the dose of ondansetron be diluted in 50 mL of 5% dextrose injection or 0.9% sodium chloride injection ^{23} ^{36}; however, ondansetron also has been shown to be stable in dextrose and sodium chloride injections, 3% sodium chloride injection ^{01} ^{22} ^{23}, 10% mannitol injection, and Ringer's injection. ^{22} ^{36}

Stability:
Intravenous infusions of ondansetron retain their potency for 48 hours at room temperature under normal lighting after dilution with 5% dextrose injection, dextrose and sodium chloride injections, 0.9% sodium chloride injection, and 3% sodium chloride injection. ^{01} ^{23}

Incompatibilities:
The following medications may be incompatible with ondansetron and should be avoided in admixtures: acyclovir, allopurinol, aminophylline, amphotericin B, ampicillin, ampicillin and sulbactam, amsacrine, cefepime, cefoperazone, furosemide, ganciclovir, lorazepam, methylprednisolone, mezlocillin, piperacillin, ^{19} ^{26} ^{36} and sargramostim. ^{36} ^{68} In addition, alkaline solutions ^{23} ^{26} ^{35} ^{36} and fluorouracil in concentrations greater than 0.8 mg per mL ^{36} ^{58} have been shown to be physically incompatible with ondansetron.

Caution:
Occasionally, ondansetron precipitates at the stopper/vial interface in vials stored upright. If a precipitate is observed, resolubilize by shaking the vial vigorously. Potency and stability are not affected. ^{67}

Revised: 05/22/2001

References

Zofran package insert (Glaxo—US), Rev 1/91, Rec 1/91.

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DeMulder 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.

Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL. Efficacy of ondansetron (GR38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med 1990; 322: 810-6.

Marty M, Pouillart P, Scholl S, et al. Comparison of the 5-Hydroxytryptamine ₃ (serotonin) antagonist ondansetron (GR38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis. N Engl J Med 1990; 322: 816-21.

Talley NJ, Phillips SF, Haddad A, et al. GR38032F (ondansetron), a selective 5HT ₃ receptor antagonist, slows colonic transit in healthy man. Dig Dis Sci 1990; 35: 477-80.

Graves T. Ondansetron: A new entity in emesis control. DICP Ann Pharmacother 1990; 24(Suppl): S51-S54.

Einhorn LH, Nagy C, Werner K, Finn AL. Ondansetron: A new antiemetic for patients receiving cisplatin chemotherapy. J Clin Oncol 1990; 8: 731-5.

Cubeddu LX, Hoffman IS, Fuenmayor NT, Finn AL. Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens. J Clin Oncol 1990; 8: 1721-7.

Hesketh PJ, Murphy WK, Lester EP, et al. GR38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis. J Clin Oncol 1989; 7: 700-5.

Tyers MB, Bunce KT, Humphrey PPA. Pharmacological and anti-emetic properties of ondansetron. Eur J Cancer Clin Oncol 1989; 25(Suppl 1): S15-S19.

Blackwell CP, Harding SM. The clinical pharmacology of ondansetron. Eur J Cancer Clin Oncol 1989; 25(Suppl 1): S21-S24.

Schmoll HJ. The role of ondansetron in the treatment of emesis induced by non-cisplatin-containing chemotherapy regimens. Eur J Cancer Clin Oncol 1989; 25(Suppl 1): S35-S39.

Marty M. Ondansetron in the prophylaxis of acute cisplatin-induced nausea and vomiting. Eur J Cancer Clin Oncol 1989; 25(Suppl 1): S41-S45.

Smith RN. Safety of ondansetron. Eur J Cancer Clin Oncol 1989; 25(Suppl 1): S47-S50.

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Ondansetron tablets package insert (Cerenex—US), Rev 9/94, Rec 10/18/94.

Manufacturer comment, 11/94.

Panel consensus on monograph revision of 11/94.

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Panel comment, 11/94.

Zofran tablets package insert (Cerenex—US), Rev 4/95, Rec 5/19/95.

Manufacturer comment, 6/95.

Manufacturer comment, 6/95.

Panel comment, 6/95.

Zofran injection package insert (Glaxo-Wellcome—US), Rev 2/96, Rec 4/8/96.

Zofran injection package insert (Glaxo-Wellcome—US), Rev 10/97, Rec 4/22/98.

Trissel LA. Handbook on injectable drugs. 9th ed. Bethesda, MD: American Society of Hospital Pharmacists; 1996. p. 820-6.

Zofran product monograph (Glaxo Wellcome—Canada), Rev 12/20/96, Rec 2/10/97.

Zofran oral solution package insert (Glaxo-Wellcome—US), Rev 10/96, Rec 3/7/97.

Zofran ODT package insert (Glaxo-Wellcome—US), Rev 1/99, Rec 2/3/99.

Product Information: Zofran, ondansetron hydrochloride, Triangle Park, N.C. (revised 12/2000) reviewed 5/2001.

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