Drugs Details

Drugs Info of Zofran
Drugs Details
  • Drugs Type  : FDA
  • Date : 25th Feb 2015 05:59 am
  • Brand Name : Zofran
  • Generic Name : ondansetron (injection) (Pronunciation: on DAN se tron)
Descriptions

The active ingredient of ZOFRAN Injection is ondansetron hydrochloride, a selective blocking agent of the serotonin 5-HT3 receptor type. Its chemical name is (±) 1, 2, 3, 9tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one, monohydrochloride, dihydrate. It has the following structural formula:

 

ZOFRAN® (ondansetron hydrochloride) Structural Formula Illustration

The empirical formula is C18H19N3O•HCl•2H2O, representing a molecular weight of 365.9.

Ondansetron HCl is a white to off-white powder that is soluble in water and normal saline.

Each 1 mL of aqueous solution in the 20 mL multidose vial contains 2 mg of ondansetron as the hydrochloride dihydrate; 8.3 mg of sodium chloride, USP; 0.5 mg of citric acid monohydrate, USP and 0.25 mg of sodium citrate dihydrate, USP as buffers; and 1.2 mg of methylparaben, NF and 0.15 mg of propylparaben, NF as preservatives in Water for Injection, USP.

ZOFRAN Injection is a clear, colorless, nonpyrogenic, sterile solution for intravenous use. The pH of the injection solution is 3.3 to 4.0.

What are the possible side effects of ondansetron (Zofran)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • fast, slow, or uneven heartbeats;
  • feeling like you might pass out; or
  • headache with chest pain and severe dizziness, fainting, fast or pounding heartbeat.

Other common side effects may include:

  • diarrhea, constipation;
  • drowsiness;
  • itching, numbness, or tingling;
  • mild headache; or
  • fever, or cold...

Read All Potential Side Effects and See Pictures of Zofran Injection »

What are the precautions when taking ondansetron hydrochloride injection (Zofran Injection)?

Before using ondansetron, tell your doctor or pharmacist if you are allergic to it; or to other serotonin blockers (e.g., granisetron); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: irregular heartbeat, liver disease, stomach/intestinal problems (e.g., recent abdominal surgery, ileus, swelling).

Ondansetron may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical...

Read All Potential Precautions of Zofran Injection »


This monograph has been modified to include the generic and brand name in many instances.

Indications

Prevention Of Nausea And Vomiting Associated With Initial And Repeat Courses Of Emetogenic Cancer Chemotherapy

ZOFRAN Injection is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin [see Clinical Studies].

ZOFRAN is approved for patients aged 6 months and older.

Prevention Of Postoperative Nausea And/Or Vomiting

ZOFRAN Injection is indicated for the prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients in whom nausea and/or vomiting must be avoided postoperatively, ZOFRAN Injection is recommended even when the incidence of postoperative nausea and/or vomiting is low. For patients who do not receive prophylactic ZOFRAN Injection and experience nausea and/or vomiting postoperatively, ZOFRAN Injection may be given to prevent further episodes [see Clinical Studies].

ZOFRAN is approved for patients aged 1 month and older.

Dosage Administration

Prevention Of Nausea And Vomiting Associated With Initial And Repeat Courses Of Emetogenic Chemotherapy

ZOFRAN Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.

Adults

The recommended adult intravenous dosage of ZOFRAN is three 0.15-mg/kg doses up to a maximum of 16 mg per dose [see CLINICAL PHARMACOLOGY]. The first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg up to a maximum of 16 mg per dose) are administered 4 and 8 hours after the first dose of ZOFRAN.

Pediatrics

For pediatric patients 6 months through 18 years of age, the intravenous dosage of ZOFRAN is three 0.15-mg/kg doses up to a maximum of 16 mg per dose [see Clinical Studies and CLINICAL PHARMACOLOGY]. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy. Subsequent doses (0.15 mg/kg up to a maximum of 16 mg per dose) are administered 4 and 8 hours after the first dose of ZOFRAN. The drug should be infused intravenously over 15 minutes.

Prevention Of Postoperative Nausea And Vomiting

ZOFRAN Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form.

Adults

The recommended adult intravenous dosage of ZOFRAN is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient did not receive prophylactic antiemetics and experiences nausea and/or vomiting occurring within 2 hours after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, intravenous dose of ondansetron 4 mg, administration of a second intravenous dose of 4 mg ondansetron postoperatively does not provide additional control of nausea and vomiting.

Pediatrics

For pediatric patients 1 month through 12 years of age, the dosage is a single 0.1-mg/kg dose for patients weighing 40 kg or less, or a single 4-mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient did not receive prophylactic antiemetics and experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic ZOFRAN.

Stability And Handling

After dilution, do not use beyond 24 hours. Although ZOFRAN Injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative.

ZOFRAN Injection is stable at room temperature under normal lighting conditions for 48 hours after dilution with the following intravenous fluids: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and 3% Sodium Chloride Injection.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

Precaution

Occasionally, ondansetron precipitates at the stopper/vial interface in vials stored upright. Potency and safety are not affected. If a precipitate is observed, resolubilize by shaking the vial vigorously.

Dosage Adjustment For Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), a single maximal daily dose of 8 mg infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron in these patients [see CLINICAL PHARMACOLOGY].

 

How Supplied

Dosage Forms And Strengths

ZOFRAN Injection, 2 mg/mL is a clear, colorless, nonpyrogenic, sterile solution available as a 20 mL multidose vial.

Storage And Handling

ZOFRAN Injection, 2 mg/mL, is supplied as follows:

NDC 0173-0442-00 20-mL multidose vials (Singles)

Storage

Store vials between 2° and 30°C (36° and 86°F). Protect from light.

GlaxoSmithKline Research Triangle Park, NC 27709. Revised: December 2013


This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The following adverse reactions have been reported in clinical trials of adult patients treated with ondansetron, the active ingredient of intravenous ZOFRAN across a range of dosages. A causal relationship to therapy with ZOFRAN (ondansetron) was unclear in many cases.

Chemotherapy-Induced Nausea and Vomiting

Table 1: Adverse Reactions Reported in > 5% of Adult Patients Who Received Ondansetron at a Dosage of Three 0.15-mg/kg Doses

Adverse Reaction Number of Adult Patients With Reaction
ZOFRAN Injection 0.15 mg/kg x 3
n = 419
Metoclopramide
n = 156
Placebo
n = 34
Diarrhea 16% 44% 18%
Headache 17% 7% 15%
Fever 8% 5% 3%

Cardiovascular: Rare cases of angina (chest pain), electrocardiographic alterations, hypotension, and tachycardia have been reported.

Gastrointestinal: Constipation has been reported in 11% of chemotherapy patients receiving multiday ondansetron.

Hepatic: In comparative trials in cisplatin chemotherapy patients with normal baseline values of aspartate transaminase (AST) and alanine transaminase (ALT), these enzymes have been reported to exceed twice the upper limit of normal in approximately 5% of patients. The increases were transient and did not appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur.

Integumentary: Rash has occurred in approximately 1% of patients receiving ondansetron.

Neurological: There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving ZOFRAN Injection, and rare cases of grand mal seizure.

Other: Rare cases of hypokalemia have been reported.

Postoperative Nausea and Vomiting

The adverse reactions in Table 2 have been reported in ≥ 2% of adults receiving ondansetron at a dosage of 4 mg intravenous over 2 to 5 minutes in clinical trials.

Table 2: Adverse Reactions Reported in ≥ 2% (and With Greater Frequency than the Placebo Group) of Adult Patients Receiving Ondansetron at a Dosage of 4 mg Intravenous over 2 to 5 Minutes

Adverse Reactiona,b ZOFRAN Injection 4 mg Intravenous
n = 547 patients
Placebo
n = 547 patients
Headache 92 (17%) 77 (14%)
Drowsiness/sedation 44 (8%) 37 (7%)
Injection site reaction 21 (4%) 18 (3%)
Fever 10 (2%) 6 (1%)
Cold sensation 9 (2%) 8 (1%)
Pruritus 9 (2%) 3 ( < 1%)
Paresthesia 9 (2%) 2 ( < 1%)
 aAdverse Reactions: Rates of these reactions were not significantly different in the ondansetron and placebo groups
bPatients were receiving multiple concomitant perioperative and postoperative medications

Pediatric Use: Rates of adverse reactions were similar in both the ondansetron and placebo groups in pediatric patients receiving ondansetron (a single 0.1-mg/kg dose for pediatric patients weighing 40 kg or less, or 4 mg for pediatric patients weighing more than 40 kg) administered intravenously over at least 30 seconds. Diarrhea was seen more frequently in patients taking ZOFRAN (2%) compared to placebo ( < 1%) in the 1 month to 24 month age group. These patients were receiving multiple concomitant perioperative and postoperative medications.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ondansetron. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ondansetron.

Cardiovascular: Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular contractions, and atrial fibrillation), bradycardia, electrocardiographic alterations (including second-degree heart block, QT/QTc interval prolongation, and ST segment depression), palpitations, and syncope. Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT/QTc interval prolongation have been reported [see WARNINGS AND PRECAUTIONS].

General: Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylactic reactions, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, stridor) have also been reported. A positive lymphocyte transformation test to ondansetron has been reported, which suggests immunologic sensitivity to ondansetron.

Hepatobiliary: Liver enzyme abnormalities have been reported. Liver failure and death have been reported in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics.

Local Reactions: Pain, redness, and burning at site of injection.

Lower Respiratory: Hiccups

Neurological: Oculogyric crisis, appearing alone, as well as with other dystonic reactions. Transient dizziness during or shortly after intravenous infusion.

Skin: Urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Eye Disorders: Cases of transient blindness, predominantly during intravenous administration, have been reported. These cases of transient blindness were reported to resolve within a few minutes up to 48 hours. Transient blurred vision, in some cases associated with abnormalities of accommodation, have also been reported.

Read the Zofran Injection (ondansetron hydrochloride injection) Side Effects Center for a complete guide to possible side effects

Interactions

Drugs Affecting Cytochrome P-450 Enzymes

Ondansetron does not appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver. Because ondansetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of ondansetron [see CLINICAL PHARMACOLOGY]. On the basis of limited available data, no dosage adjustment is recommended for patients on these drugs.

Apomorphine

Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with ondansetron is contraindicated [see CONTRAINDICATIONS].

Phenytoin, Carbamazepine, And Rifampin

In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. However, on the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs [see CLINICAL PHARMACOLOGY].

Tramadol

Although there are no data on pharmacokinetic drug interactions between ondansetron and tramadol, data from two small studies indicate that concomitant use of ondansetron may result in reduced analgesic activity of tramadol. Patients on concomitant ondansetron self administered tramadol more frequently in these studies, leading to an increased cumulative dose in patient controlled administration (PCA) of tramadol.

Chemotherapy

In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.

In a crossover study in 76 pediatric patients, intravenous ondansetron did not increase blood levels of high-dose methotrexate.

Temazepam

The coadministration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.

Alfentanil And Atracurium

Ondansetron does not alter the respiratory depressant effects produced by alfentanil or the degree of neuromuscular blockade produced by atracurium. Interactions with general or local anesthetics have not been studied.

Drug Abuse And Dependence

Animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.


This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.

QT Prolongation

Ondansetron prolongs the QT interval in a dose-dependent manner [see CLINICAL PHARMACOLOGY]. In addition, post-marketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ZOFRAN in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking other medicinal products that lead to QT prolongation.

Masking Of Progressive Ileus And Gastric Distension

The use of ZOFRAN in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and gastric distention.

Effect On Peristalsis

ZOFRAN is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to 10 and 30 mg/kg per day, respectively (approximately 3.6 and 5.4 times the recommended human intravenous dose of 0.15 mg/kg given three times a day, based on body surface area). Ondansetron was not mutagenic in standard tests for mutagenicity.

Oral administration of ondansetron up to 15 mg/kg per day (approximately 3.8 times the recommended human intravenous dose, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.

Use In Specific Populations

Pregnancy

Pregnancy Category B

Reproduction studies have been performed in pregnant rats and rabbits at intravenous doses up to 4 mg/kg per day (approximately 1.4 and 2.9 times the recommended human intravenous dose of 0.15 mg/kg given three times a day, respectively, based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Ondansetron is excreted in the breast milk of rats. It is not known whether ondansetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ondansetron is administered to a nursing woman.

Pediatric Use

Little information is available about the use of ondansetron in pediatric surgical patients younger than 1 month of age. [See Clinical Studies]. Little information is available about the use of ondansetron in pediatric cancer patients younger than 6 months of age. [See Clinical Studies and DOSAGE AND ADMINISTRATION].

The clearance of ondansetron in pediatric patients 1 month to 4 months of age is slower and the half-life is ~2.5 fold longer than patients who are > 4 to 24 months of age. As a precaution, it is recommended that patients less than 4 months of age receiving this drug be closely monitored. [See CLINICAL PHARMACOLOGY].

Geriatric Use

Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US- and foreign-controlled clinical trials, 862 were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Dosage adjustment is not needed in patients over the age of 65 [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life [see CLINICAL PHARMACOLOGY]. In such patients, a total daily dose of 8 mg should not be exceeded [see DOSAGE AND ADMINISTRATION].

Renal Impairment

Although plasma clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 mL/min), no dosage adjustment is recommended [see CLINICAL PHARMACOLOGY].


This monograph has been modified to include the generic and brand name in many instances.

OverDose

There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy. Individual intravenous doses as large as 150 mg and total daily intravenous doses as large as 252 mg have been inadvertently administered without significant adverse events. These doses are more than 10 times the recommended daily dose.

In addition to the adverse reactions listed above, the following events have been described in the setting of ondansetron overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes' duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose. Hypotension (and faintness) occurred in another patient that took 48 mg of ondansetron hydrochloride tablets. Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed. In all instances, the events resolved completely.

ContrainDications

ZOFRAN Injection is contraindicated for patients known to have hypersensitivity (e.g., anaphylaxis) to this product or any of its components. Anaphylactic reactions have been reported in patients taking ondansetron. [See ADVERSE REACTIONS].

The concomitant use of apomorphine with ondansetron is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron.
This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism Of Action

Ondansetron is a selective 5-HT3 receptor antagonist. While ondansetron's mechanism of action has not been fully characterized, it is not a dopamine-receptor antagonist.

Pharmacodynamics

QTc interval prolongation was studied in a double blind, single intravenous dose, placebo- and positive-controlled, crossover study in 58 healthy subjects. The maximum mean (95% upper confidence bound) difference in QTcF from placebo after baseline-correction was 19.5 (21.8) ms and 5.6 (7.4) ms after 15 minute intravenous infusions of 32mg and 8 mg ZOFRAN, respectively. A significant exposure-reponse relationship was identified between ondansetron concentration and δδQTcF. Using the established exposure-response relationship, 24 mg infused intravenously over 15 min had a mean predicted (95% upper prediction interval) δδQTcF of 14.0 (16.3) ms. In contrast, 16 mg infused intravenously over 15 min using the same model had a mean predicted (95% upper prediction interval) δδQTcF of 9.1 (11.2) ms.

In normal volunteers, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. In another study in six normal male volunteers, a 16-mg dose infused over 5 minutes showed no effect of the drug on cardiac output, heart rate, stroke volume, blood pressure, or electrocardiogram (ECG). Multiday administration of ondansetron has been shown to slow colonic transit in normal volunteers. Ondansetron has no effect on plasma prolactin concentrations.In a gender-balanced pharmacodynamic study (n = 56), ondansetron 4 mg administered intravenously or intramuscularly was dynamically similar in the prevention of nausea and vomiting using the ipecacuanha model of emesis.

Pharmacokinetics

In normal adult volunteers, the following mean pharmacokinetic data have been determined following a single 0.15-mg/kg intravenous dose.

Table 3: Pharmacokinetics in Normal Adult Volunteers

Age-group (years) n Peak Plasma Concentration (ng/mL) Mean Elimination Half-life (h) Plasma Clearance (L/h/kg)
19-40 11 102 3.5 0.381
61-74 12 106 4.7 0.319
≥ 75 11 170 5.5 0.262
Absorption

A study was performed in normal volunteers (n = 56) to evaluate the pharmacokinetics of a single 4-mg dose administered as a 5-minute infusion compared to a single intramuscular injection. Systemic exposure as measured by mean AUC were equivalent, with values of 156 [95% CI 136, 180] and 161 [95% CI 137, 190] ng•h/mL for intravenous and intramuscular groups, respectively. Mean peak plasma concentrations were 42.9 [95% CI 33.8, 54.4] ng/mL at 10 minutes after intravenous infusion and 31.9 [95% CI 26.3, 38.6] ng/mL at 41 minutes after intramuscular injection.

Distribution

Plasma protein binding of ondansetron as measured in vitro was 70% to 76%, over the pharmacologic concentration range of 10 to 500 ng/mL. Circulating drug also distributes into erythrocytes.

Metabolism

Ondansetron is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation.

Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of ondansetron. The metabolites are observed in the urine.

In vitro metabolism studies have shown that ondansetron is a substrate for multiple human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. In terms of overall ondansetron turnover, CYP3A4 plays a predominant role while formation of the major in vivo metabolites is apparently mediated by CYP1A2. The role of CYP2D6 in ondansetron in vivo metabolism is relatively minor.

The pharmacokinetics of intravenous ondansetron did not differ between subjects who were poor metabolisers of CYP2D6 and those who were extensive metabolisers of CYP2D6, further supporting the limited role of CYP2D6 in ondansetron disposition in vivo.

Elimination

In adult cancer patients, the mean ondansetron elimination half-life was 4.0 hours, and there was no difference in the multidose pharmacokinetics over a 4-day period. In a dose proportionality study, systemic exposure to 32 mg of ondansetron was not proportional to dose as measured by comparing dose-normalized AUC values to an 8-mg dose. This is consistent with a small decrease in systemic clearance with increasing plasma concentrations.

Geriatrics

A reduction in clearance and increase in elimination half-life are seen in patients over 75 years of age. In clinical trials with cancer patients, safety and efficacy were similar in patients over 65 years of age and those under 65 years of age; there was an insufficient number of patients over 75 years of age to permit conclusions in that age-group. No dosage adjustment is recommended in the elderly.

Pediatrics

Pharmacokinetic samples were collected from 74 cancer patients 6 to 48 months of age, who received a dose of 0.15 mg/kg of intravenous ondansetron every 4 hours for 3 doses during a safety and efficacy trial. These data were combined with sequential pharmacokinetics data from 41 surgery patients 1 month to 24 months of age, who received a single dose of 0.1 mg/kg of intravenous ondansetron prior to surgery with general anesthesia, and a population pharmacokinetic analysis was performed on the combined data set. The results of this analysis are included in Table 4 and are compared to the pharmacokinetic results in cancer patients 4 to 18 years of age.

Table 4: Pharmacokinetics in Pediatric Cancer Patients 1 Month to 18 Years of Age

Subjects and Age Group N CL (L/h/kg) Vdss (L/kg) T½ (h)
  Geometric Mean Mean
Pediatric Cancer Patients 4 to 18 years of age N = 21 0.599 1.9 2.8
Population PK Patientsa 1 month to 48 months of age N = 115 0.582 3.65 4.9
aPopulation PK (Pharmacokinetic) Patients: 64% cancer patients and 36% surgery patients.

Based on the population pharmacokinetic analysis, cancer patients 6 to 48 months of age who receive a dose of 0.15 mg/kg of intravenous ondansetron every 4 hours for 3 doses would be expected to achieve a systemic exposure (AUC) consistent with the exposure achieved in previous pediatric studies in cancer patients (4 to 18 years of age) at similar doses.

In a study of 21 pediatric patients (3 to 12 years of age) who were undergoing surgery requiring anesthesia for a duration of 45 minutes to 2 hours, a single intravenous dose of ondansetron, 2 mg (3 to 7 years) or 4 mg (8 to 12 years), was administered immediately prior to anesthesia induction. Mean weight-normalized clearance and volume of distribution values in these pediatric surgical patients were similar to those previously reported for young adults. Mean terminal half-life was slightly reduced in pediatric patients (range, 2.5 to 3 hours) in comparison with adults (range, 3 to 3.5 hours).

In a study of 51 pediatric patients (1 month to 24 months of age) who were undergoing surgery requiring general anesthesia, a single intravenous dose of ondansetron, 0.1 or 0.2 mg/kg, was administered prior to surgery. As shown in Table 5, the 41 patients with pharmacokinetic data were divided into 2 groups, patients 1 month to 4 months of age and patients 5 to 24 months of age, and are compared to pediatric patients 3 to 12 years of age.

Table 5: Pharmacokinetics in Pediatric Surgery Patients 1 Month to 12 Years of Age

Subjects and Age Group N CL (L/h/kg) Vdss (L/kg) T½ (h)
Geometric Mean Mean
Pediatric Surgery Patients 3 to 12 years of age N = 21 0.439 1.65 2.9
Pediatric Surgery Patients 5 to 24 months of age N = 22 0.581 2.3 2.9
Pediatric Surgery Patients 1 month to 4 months of age N = 19 0.401 3.5 6.7

In general, surgical and cancer pediatric patients younger than 18 years tend to have a higher ondansetron clearance compared to adults leading to a shorter half-life in most pediatric patients. In patients 1 month to 4 months of age, a longer half-life was observed due to the higher volume of distribution in this age group.

In a study of 21 pediatric cancer patients (4 to 18 years of age) who received three intravenous doses of 0.15 mg/kg of ondansetron at 4-hour intervals, patients older than 15 years of age exhibited ondansetron pharmacokinetic parameters similar to those of adults.

Renal Impairment

Due to the very small contribution (5%) of renal clearance to the overall clearance, renal impairment was not expected to significantly influence the total clearance of ondansetron. However, ondansetron mean plasma clearance was reduced by about 41% in patients with severe renal impairment (creatinine clearance < 30 mL/min). This reduction in clearance is variable and was not consistent with an increase in half-life. No reduction in dose or dosing frequency in these patients is warranted.

Hepatic Impairment

In patients with mild-to-moderate hepatic impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours compared to 5.7 hours in those without hepatic impairment. In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced 2-fold to 3-fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours. In patients with severe hepatic impairment, a total daily dose of 8 mg should not be exceeded.

Clinical Studies

The clinical efficacy of ondansetron hydrochloride, the active ingredient of ZOFRAN, was assessed in clinical trials as described below.

Chemotherapy-Induced Nausea and Vomiting

Adults: In a double-blind study of three different dosing regimens of ZOFRAN Injection, 0.015 mg/kg, 0.15 mg/kg, and 0.30 mg/kg, each given three times during the course of cancer chemotherapy, the 0.15-mg/kg dosing regimen was more effective than the 0.015-mg/kg dosing regimen. The 0.30-mg/kg dosing regimen was not shown to be more effective than the 0.15-mg/kg dosing regimen.

Cisplatin-Based Chemotherapy: In a double-blind study in 28 patients, ZOFRAN Injection (three 0.15-mg/kg doses) was significantly more effective than placebo in preventing nausea and vomiting induced by cisplatin-based chemotherapy. Therapeutic response was as shown in Table 6.

Table 6: Therapeutic Response in Prevention of Chemotherapy-Induced Nausea and Vomiting in Single-Day Cisplatin Therapya in Adults

  ZOFRAN Injection (0.15 mg/kg x 3) Placebo P Valueb
Number of patients 14 14  
Treatment response      
  0 Emetic episodes 2 (14%) 0 (0%)  
  1-2 Emetic episodes 8 (57%) 0 (0%)  
  3-5 Emetic episodes 2 (14%) 1 (7%)  
  More than 5 emetic episodes/rescued 2 (14%) 13 (93%) 0.001
Median number of emetic episodes 1.5 Undefinedc  
Median time to first emetic episode (h) 11.6 2.8 0.001
Median nausea scores (0-100)d 3 59 0.034
Global satisfaction with control of nausea and vomiting (0-100)e 96 10.5 0.009
aChemotherapy was high dose (100 and 120 mg/m²; ZOFRAN Injection n = 6, placebo n = 5) or moderate dose (50 and 80 mg/m²; ZOFRAN Injection n = 8, placebo n = 9). Other chemotherapeutic agents included fluorouracil, doxorubicin, and cyclophosphamide. There was no difference between treatments in the types of chemotherapy that would account for differences in response.
bEfficacy based on “all patients treated” analysis.
cMedian undefined since at least 50% of the patients were rescued or had more than five emetic episodes.
dVisual analog scale assessment of nausea: 0 = no nausea, 100 = nausea as bad as it can be.
eVisual analog scale assessment of satisfaction: 0 = not at all satisfied, 100 = totally satisfied.

Ondansetron injection (0.15-mg/kg x 3 doses) was compared with metoclopramide (2 mg/kg x 6 doses) in a single-blind trial in 307 patients receiving cisplatin ≥ 100 mg/m² with or without other chemotherapeutic agents. Patients received the first dose of ondansetron or metoclopramide 30 minutes before cisplatin. Two additional ondansetron doses were administered 4 and 8 hours later, or five additional metoclopramide doses were administered 2, 4, 7, 10, and 13 hours later. Cisplatin was administered over a period of 3 hours or less. Episodes of vomiting and retching were tabulated over the period of 24 hours after cisplatin. The results of this study are summarized in Table 7.

Table 7: Therapeutic Response in Prevention of Vomiting Induced by Cisplatin ( ≥ 100 mg/m²) Single-Day Therapya in Adults

  ZOFRAN Injection Metoclopramide P Value
Dose 0.15 mg/kg x 3 2 mg/kg x 6  
Number of patients in efficacy population 136 138  
Treatment response      
  0 Emetic episodes 54 (40%) 41 (30%)  
  1-2 Emetic episodes 34 (25%) 30 (22%)  
  3-5 Emetic episodes 19 (14%) 18 (13%)  
  More than 5 emetic episodes/rescued 29 (21%) 49 (36%)  
Comparison of treatments with respect to      
  0 Emetic episodes 54/136 41/138 0.083
  More than 5 emetic episodes/rescued 29/136 49/138 0.009
Median number of emetic episodes 1 2 0.005
Median time to first emetic episode (h) 20.5 4.3 < 0.001
Global satisfaction with control of nausea and vomiting (0-100)b 85 63 0.001
Acute dystonic reactions 0 8 0.005
Akathisia 0 10 0.002
aIn addition to cisplatin, 68% of patients received other chemotherapeutic agents, including cyclophosphamide, etoposide, and fluorouracil. There was no difference between treatments in the types of chemotherapy that would account for differences in response.
bVisual analog scale assessment: 0 = not at all satisfied, 100 = totally satisfied.

Cyclophosphamide-Based Chemotherapy: In a double-blind, placebo-controlled study of ZOFRAN Injection (three 0.15-mg/kg doses) in 20 patients receiving cyclophosphamide (500 to 600 mg/m²) chemotherapy, ZOFRAN Injection was significantly more effective than placebo in preventing nausea and vomiting. The results are summarized in Table 8.

Table 8: Therapeutic Response in Prevention of Chemotherapy-Induced Nausea and Vomiting in Single-Day Cyclophosphamide Therapya in Adults

  ZOFRAN Injection (0.15 mg/kg x 3) Placebo P Valueb
Number of patients 10 10  
Treatment response      
  0 Emetic episodes 7 (70%) 0 (0%) 0.001
  1-2 Emetic episodes 0 (0%) 2 (20%)  
  3-5 Emetic episodes 2 (20%) 4 (40%)  
  More than 5 emetic episodes/rescued 1 (10%) 4 (40%) 0.131
Median number of emetic episodes 0 4 0.008
Median time to first emetic episode (h) Undefinedc 8.79  
Median nausea scores (0-100)d 0 60 0.001
Global satisfaction with control of nausea and vomiting (0-100)e 100 52 0.008
aChemotherapy consisted of cyclophosphamide in all patients, plus other agents, including fluorouracil, doxorubicin, methotrexate, and vincristine. There was no difference between treatments in the type of chemotherapy that would account for differences in response.
bEfficacy based on “all patients treated” analysis.
cMedian undefined since at least 50% of patients did not have any emetic episodes.
dVisual analog scale assessment of nausea: 0 = no nausea, 100 = nausea as bad as it can be.
eVisual analog scale assessment of satisfaction: 0 = not at all satisfied, 100 = totally satisfied.

Re-treatment: In uncontrolled trials, 127 patients receiving cisplatin (median dose, 100 mg/m²) and ondansetron who had two or fewer emetic episodes were re-treated with ondansetron and chemotherapy, mainly cisplatin, for a total of 269 re-treatment courses (median, 2; range, 1 to 10). No emetic episodes occurred in 160 (59%), and two or fewer emetic episodes occurred in 217 (81%) re-treatment courses.

Pediatrics

Four open-label, noncomparative (one US, three foreign) trials have been performed with 209 pediatric cancer patients 4 to 18 years of age given a variety of cisplatin or noncisplatin regimens. In the three foreign trials, the initial ZOFRAN Injection dose ranged from 0.04 to 0.87 mg/kg for a total dose of 2.16 to 12 mg. This was followed by the oral administration of ondansetron ranging from 4 to 24 mg daily for 3 days. In the US trial, ZOFRAN was administered intravenously (only) in three doses of 0.15 mg/kg each for a total daily dose of 7.2 to 39 mg. In these studies, 58% of the 196 evaluable patients had a complete response (no emetic episodes) on day 1. Thus, prevention of vomiting in these pediatric patients was essentially the same as for patients older than 18 years of age.

An open-label, multicenter, noncomparative trial has been performed in 75 pediatric cancer patients 6 to 48 months of age receiving at least one moderately or highly emetogenic chemotherapeutic agent. Fifty-seven percent (57%) were females; 67% were white, 18% were American Hispanic, and 15% were black patients. ZOFRAN was administered intravenously over 15 minutes in three doses of 0.15 mg/kg. The first dose was administered 30 minutes before the start of chemotherapy, the second and third doses were administered 4 and 8 hours after the first dose, respectively. Eighteen patients (25%) received routine prophylactic dexamethasone (i.e., not given as rescue). Of the 75 evaluable patients, 56% had a complete response (no emetic episodes) on day 1. Thus, prevention of vomiting in these pediatric patients was comparable to the prevention of vomiting in patients 4 years of age and older.

Prevention Of Postoperative Nausea And/Or Vomiting

Adults

Adult surgical patients who received ondansetron immediately before the induction of general balanced anesthesia (barbiturate: thiopental, methohexital, or thiamylal; opioid: alfentanil or fentanyl; nitrous oxide; neuromuscular blockade: succinylcholine/curare and/or vecuronium or atracurium; and supplemental isoflurane) were evaluated in two double-blind US studies involving 554 patients. ZOFRAN Injection (4 mg) intravenous given over 2 to 5 minutes was significantly more effective than placebo. The results of these studies are summarized in Table 9.

Table 9: Therapeutic Response in Prevention of Postoperative Nausea and Vomiting in Adult Patients

  Ondansetron 4 mg Intravenous Placebo P Value
Study 1
Emetic episodes:      
Number of patients 136 139  
Treatment response over 24-h postoperative period      
0 Emetic episodes 103 (76%) 64 (46%) < 0.001
1 Emetic episode 13 (10%) 17 (12%)  
More than 1 emetic episode/rescued 20 (15%) 58 (42%)  
Nausea assessments:      
Number of patients 134 136  
No nausea over 24-h postoperative period 56 (42%) 39 (29%)  
Study 2
Emetic episodes:      
Number of patients 136 143  
Treatment response over 24-h postoperative period      
0 Emetic episodes 85 (63%) 63 (44%) 0.002
1 Emetic episode 16 (12%) 29 (20%)  
More than 1 emetic episode/rescued 35 (26%) 51 (36%)  
Nausea assessments:      
Number of patients 125 133  
No nausea over 24-h postoperative period 48 (38%) 42 (32%)  

The study populations in Table 9 consisted mainly of females undergoing laparoscopic procedures.

In a placebo-controlled study conducted in 468 males undergoing outpatient procedures, a single 4-mg intravenous ondansetron dose prevented postoperative vomiting over a 24-hour study period in 79% of males receiving drug compared to 63% of males receiving placebo (P < 0.001).

Two other placebo-controlled studies were conducted in 2,792 patients undergoing major abdominal or gynecological surgeries to evaluate a single 4-mg or 8-mg intravenous ondansetron dose for prevention of postoperative nausea and vomiting over a 24-hour study period. At the 4-mg dosage, 59% of patients receiving ondansetron versus 45% receiving placebo in the first study (P < 0.001) and 41% of patients receiving ondansetron versus 30% receiving placebo in the second study (P = 0.001) experienced no emetic episodes. No additional benefit was observed in patients who received intravenous ondansetron 8 mg compared to patients who received intravenous ondansetron 4 mg.

Pediatrics

Three double-blind, placebo-controlled studies have been performed (one US, two foreign) in 1,049 male and female patients (2 to 12 years of age) undergoing general anesthesia with nitrous oxide. The surgical procedures included tonsillectomy with or without adenoidectomy, strabismus surgery, herniorrhaphy, and orchidopexy. Patients were randomized to either single intravenous doses of ondansetron (0.1 mg/kg for pediatric patients weighing 40 kg or less, 4 mg for pediatric patients weighing more than 40 kg) or placebo. Study drug was administered over at least 30 seconds, immediately prior to or following anesthesia induction. Ondansetron was significantly more effective than placebo in preventing nausea and vomiting. The results of these studies are summarized in Table 10.

Table 10: Therapeutic Response in Prevention of Postoperative Nausea and Vomiting in Pediatric Patients 2 to 12 Years of Age

Treatment Response Over 24 Hours Ondansetron
n (%)
Placebo
n (%)
P Value
Study 1
Number of patients 205 210  
0 Emetic episodes 140 (68%) 82 (39%) ≤ 0.001
Failurea 65 (32%) 128 (61%)  
Study 2
Number of patients 112 110  
0 Emetic episodes 68 (61%) 38 (35%) ≤ 0.001
Failurea 44 (39%) 72 (65%)  
Study 3
Number of patients 206 206  
0 Emetic episodes 123 (60%) 96 (47%) ≤ 0.01
Failurea 83 (40%) 110 (53%)  
Nausea assessmentsb:
Number of patients 185 191  
None 119 (64%) 99 (52%) ≤ 0.01
aFailure was one or more emetic episodes, rescued, or withdrawn.
bNausea measured as none, mild, or severe.

A double-blind, multicenter, placebo-controlled study was conducted in 670 pediatric patients 1 month to 24 months of age who were undergoing routine surgery under general anesthesia. Seventy-five percent (75%) were males; 64% were white, 15% were black, 13% were American Hispanic, 2% were Asian, and 6% were “other race” patients. A single 0.1-mg/kg intravenous dose of ondansetron administered within 5 minutes following induction of anesthesia was statistically significantly more effective than placebo in preventing vomiting. In the placebo group, 28% of patients experienced vomiting compared to 11% of subjects who received ondansetron (P ≤ 0.01). Overall, 32 (10%) of placebo patients and 18 (5%) of patients who received ondansetron received antiemetic rescue medication(s) or prematurely withdrew from the study.

Prevention Of Further Postoperative Nausea And Vomiting

Adults

Adult surgical patients receiving general balanced anesthesia (barbiturate: thiopental, methohexital, or thiamylal; opioid: alfentanil or fentanyl; nitrous oxide; neuromuscular blockade: succinylcholine/curare and/or vecuronium or atracurium; and supplemental isoflurane) who received no prophylactic antiemetics and who experienced nausea and/or vomiting within 2 hours postoperatively were evaluated in two double-blind US studies involving 441 patients. Patients who experienced an episode of postoperative nausea and/or vomiting were given ZOFRAN Injection (4 mg) intravenous over 2 to 5 minutes, and this was significantly more effective than placebo. The results of these studies are summarized in Table 11.

Table 11: Therapeutic Response in Prevention of Further Postoperative Nausea and Vomiting in Adult Patients

  Ondansetron 4 mg Intravenous Placebo P Value
Study 1
Emetic episodes:      
Number of patients Treatment response 24 h after study drug 104 117  
  0 Emetic episodes 49 (47%) 19 (16%) < 0.001
  1 Emetic episode 12 (12%) 9 (8%)  
  More than 1 emetic episode/rescued 43 (41%) 89 (76%)  
Median time to first emetic episode (min)a 55 43  
Nausea assessments:
Number of patients 98 102  
Mean nausea score over 24-h postoperative periodb 1.7 3.1  
Study 2
Emetic episodes:
Number of patients Treatment response 24 h after study drug 112 108  
  0 Emetic episodes 49 (44%) 28 (26%) 0.006
  1 Emetic episode 14 (13%) 3 (3%)  
  More than 1 emetic episode/rescued 49 (44%) 77 (71%)  
Median time to first emetic episode (min)a 60.5 34  
Nausea assessments:
Number of patients 105 85  
Mean nausea score over 24-h postoperative periodb 1.9 2.9  
aAfter administration of study drug.
bNausea measured on a scale of 0-10 with 0 = no nausea, 10 = nausea as bad as it can be.

The study populations in Table 11 consisted mainly of women undergoing laparoscopic procedures.

Repeat Dosing in Adults: In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, intravenous dose of ondansetron 4 mg, administration of a second intravenous dose of ondansetron 4 mg postoperatively does not provide additional control of nausea and vomiting.

Pediatrics

One double-blind, placebo-controlled, US study was performed in 351 male and female outpatients (2 to 12 years of age) who received general anesthesia with nitrous oxide and no prophylactic antiemetics. Surgical procedures were unrestricted. Patients who experienced two or more emetic episodes within 2 hours following discontinuation of nitrous oxide were randomized to either single intravenous doses of ondansetron (0.1 mg/kg for pediatric patients weighing 40 kg or less, 4 mg for pediatric patients weighing more than 40 kg) or placebo administered over at least 30 seconds. Ondansetron was significantly more effective than placebo in preventing further episodes of nausea and vomiting. The results of the study are summarized in Table 12.

Table 12: Therapeutic Response in Prevention of Further Postoperative Nausea and Vomiting in Pediatric Patients 2 to 12 Years of Age

Treatment Response Over 24 Hours Ondansetron
n (%)
Placebo
n (%)
P Value
Number of patients 180 171  
0 Emetic episodes 96 (53%) 29 (17%) ≤ 0.001
Failurea 84 (47%) 142 (83%)  
aFailure was one or more emetic episodes, rescued, or withdrawn.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

  • Patients should be informed that ZOFRAN may cause serious cardiac arrhythmias such as QT prolongation. Patients should be instructed to tell their healthcare provider right away if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode.
  • Patients should be informed that the chances of developing severe cardiac arrhythmias such as QT prolongation and Torsade de Pointes are higher in the following people:
    • Patients with a personal or family history of abnormal heart rhythms, such as congenital long QT syndrome;
    • Patients who take medications, such as diuretics, which may cause electrolyte abnormalities
    • Patients with hypokalemia or hypomagnesemia
      ZOFRAN should be avoided in these patients, since they may be more at risk for cardiac arrhythmias such as QT prolongation and Torsade de Pointes.
  • Inform patients that ZOFRAN may cause hypersensitivity reactions, some as severe as anaphylaxis and bronchospasm. The patient should report any signs and symptoms of hypersensitivity reactions, including fever, chills, rash, or breathing problems.
  • The patient should report the use of all medications, especially apomorphine, to their healthcare provider. Concomitant use of apomorphine and ZOFRAN may cause a significant drop in blood pressure and loss of consciousness.
  • Inform patients that ZOFRAN may cause headache, drowsiness/sedation, constipation, fever and diarrhea.


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

ONDANSETRON - INJECTION

 

(on-DANS-eh-tron)

 

COMMON BRAND NAME(S): Zofran

 

USES: This medication is used alone or with other medications to prevent nausea and vomiting caused by cancer chemotherapy. It is also used to prevent and treat nausea and vomiting after surgery. It works by blocking one of the body's natural substances (serotonin) that causes vomiting.

 

HOW TO USE: To prevent nausea from chemotherapy, ondansetron is mixed in a solution and given by injection into a vein as directed by your doctor, usually over 15 minutes. This drug is usually started 30 minutes before your chemotherapy treatment begins. Do not give this medication any faster than recommended or take more than the recommended dose because this may increase the chance of serious side effects such as blurred vision or slowed/irregular heartbeat. The usual maximum single dose is 16 milligrams. Depending on the type of chemotherapy treatment you are receiving, a second and third dose may be given 4 and 8 hours after your first dose. You may also be switched to a medication you can take by mouth.

Your doctor may direct you to continue this medication for 1 or 2 days after your chemotherapy treatment. If you are using this medication on a prescribed schedule, use it regularly to get the most benefit from it. To help you remember, use it at the same times each day. Use this medication exactly as directed. Do not use more medication or use it more often than prescribed. Ask your doctor or pharmacist if you have questions.

If you are giving this medication to yourself at home, learn all preparation and usage instructions from your health care professional. When the vial is stored upright after first use, clumps may occasionally form on the top of the vial. Check the vial and the vial top carefully for particles. If particles are present, shake the vial to re-dissolve the particles. If any particles remain after the vial is shaken, do not use the liquid. Ondansetron injection should be clear and colorless. If you are using the premixed bags, after removing the bag from the outer wrapper, check for small leaks by squeezing the container firmly. Before using, check visually for leaks, particles, or discoloration. If these are present or the container is damaged, do not use the liquid. Learn how to store and discard medical supplies safely.

To prevent or treat nausea after surgery, a single dose of ondansetron may be given undiluted into a muscle or vein (IV) shortly before the start of surgery, during surgery, or after surgery by a health care professional.

Dosage is based on your weight, medical condition, and response to treatment.

Tell your doctor if your condition does not improve or if it worsens.

Consumer Overview Side Effect

SIDE EFFECTS: Headache, fever, lightheadedness, dizziness, drowsiness, tiredness, constipation, or redness/pain/burning at the injection site may occur. If these effects persist or worsen, notify your doctor promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: stomach pain, muscle stiffness/spasm, vision changes (e.g., temporary loss of vision, blurred vision, uncontrollable eye movements).

Get medical help right away if any of these rare but very serious side effects occur: chest pain, slow/fast/irregular heartbeat, severe dizziness, fainting.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Zofran Injection (ondansetron hydrochloride injection) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before using ondansetron, tell your doctor or pharmacist if you are allergic to it; or to other serotonin blockers (e.g., granisetron); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: irregular heartbeat, liver disease, stomach/intestinal problems (e.g., recent abdominal surgery, ileus, swelling).

Ondansetron may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using ondansetron, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using ondansetron safely.

This drug may make you dizzy or drowsy or cause blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages.

Infants younger than 5 months may be more sensitive to the effects of this drug, especially diarrhea.

Older adults may be more sensitive to the side effects of this drug, especially QT prolongation (see above).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this drug passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: apomorphine, tramadol.

Many drugs besides ondansetron may affect the heart rhythm (QT prolongation), including dofetilide, pimozide, procainamide, amiodarone, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Therefore, before using ondansetron, report all medications you are currently using to your doctor or pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: change in vision, severe dizziness, irregular heartbeat.

 

NOTES: Laboratory and/or medical tests (such as EKG) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: It is important that the dose be given before cancer chemotherapy as directed. If you miss a dose, contact your doctor or pharmacist to establish a new dose schedule. If you are using this medication on a regular schedule and you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Consult the product instructions and your pharmacist for storage details. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

 

Information last revised March 2013. Copyright(c) 2013 First Databank, Inc.

 

Patient Detailed Side Effect

Brand Names: Zofran

Generic Name: ondansetron (injection) (Pronunciation: on DAN se tron)

  • What is ondansetron (Zofran Injection)?
  • What are the possible side effects of ondansetron (Zofran Injection)?
  • What is the most important information I should know about ondansetron (Zofran Injection)?
  • What should I discuss with my healthcare provider before taking ondansetron (Zofran Injection)?
  • How should I take ondansetron (Zofran Injection)?
  • What happens if I miss a dose (Zofran Injection)?
  • What happens if I overdose (Zofran Injection)?
  • What should I avoid while taking ondansetron (Zofran Injection)?
  • What other drugs will affect ondansetron (Zofran Injection)?
  • Where can I get more information?

What is ondansetron (Zofran Injection)?

Ondansetron blocks the actions of chemicals in the body that can trigger nausea and vomiting.

Ondansetron injection is used to prevent nausea and vomiting that may be caused by surgery or medicine to treat cancer (chemotherapy).

Ondansetron injection may also be used for purposes not listed in this medication guide.

What are the possible side effects of ondansetron (Zofran Injection)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • fast, slow, or uneven heartbeats;
  • feeling like you might pass out; or
  • headache with chest pain and severe dizziness, fainting, fast or pounding heartbeat.

Other common side effects may include:

  • diarrhea, constipation;
  • drowsiness;
  • itching, numbness, or tingling;
  • mild headache; or
  • fever, or cold feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Zofran Injection (ondansetron hydrochloride injection) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about ondansetron (Zofran Injection)?

You should not use ondansetron if you are allergic to it, or if you are also using apomorphine (Apokyn).

You should not use this medication if you have a history of Long QT syndrome. Ondansetron can cause serious heart rhythm problems.

Before receiving ondansetron injection, tell your doctor if you have liver disease, heart disease, a heart rhythm disorder, congestive heart failure, or low potassium or magnesium levels in your blood.

Tell your doctor about all other medicines you use. There are many other medicines that can increase your risk of heart rhythm problems if you use them together with ondansetron.

Call your doctor at once if you have fast, slow, or uneven heartbeats, or if you feel like you might pass out.

Side Effects Centers
  • Zofran Injection

Patient Detailed How Take

What should I discuss with my healthcare provider before taking ondansetron (Zofran Injection)?

You should not use ondansetron if you are allergic to it, or if you are also using apomorphine (Apokyn).

Ondansetron can cause serious heart rhythm problems. You should not use this medication if you have a history of Long QT syndrome. Tell your doctor if anyone in your family has ever had this condition.

To make sure ondansetron is safe for you, tell your doctor if you have:

  • liver disease;
  • a serious heart condition or heart rhythm disorder;
  • slow or fast heartbeats, or heart block;
  • congestive heart failure;
  • an electrolyte imbalance (such as low levels of potassium or magnesium in your blood); or
  • if you are allergic to medicines similar to ondansetron, such dolasetron (Anzemet), granisetron (Kytril), or palonosetron (Aloxi).

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether ondansetron passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

How should I take ondansetron (Zofran Injection)?

Ondansetron is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.

Ondansetron is usually given just before your surgery begins, or within 2 hours after surgery.

To prevent nausea and vomiting caused by chemotherapy, ondansetron is given 30 minutes before the start of chemotherapy. A second and third dose of ondansetron are sometimes given 4 hours and 8 hours after the first dose.

Ondansetron injection is not for preventing nausea or vomiting that is caused by factors other than chemotherapy or surgery.

Side Effects Centers
  • Zofran Injection

Patient Detailed Avoid Taking

What happens if I miss a dose (Zofran Injection)?

Since ondansetron is given by a healthcare professional, you are not likely to miss a dose.

What happens if I overdose (Zofran Injection)?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while taking ondansetron (Zofran Injection)?

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

What other drugs will affect ondansetron (Zofran Injection)?

There are many other medicines that can increase your risk of heart rhythm problems if you use them together with ondansetron.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with ondansetron, especially:

  • arsenic trioxide;
  • methadone;
  • tacrolimus;
  • tramadol;
  • an antibiotic such as clarithromycin, erythromycin, levofloxacin, moxifloxacin, or pentamidine;
  • an antidepressant such as amitriptyline, clomipramine, or desipramine;
  • anti-malaria medications such as chloroquine or mefloquine;
  • heart rhythm medicine such as amiodarone, dofetilide, disopyramide, dronedarone, ibutilide, procainamide, propafenone, quinidine, or sotalol;
  • other medicines to prevent or treat nausea and vomiting such as dolasetron or droperidol;
  • medicines to treat psychiatric disorders, such as chlorpromazine, clozapine, haloperidol, pimozide, thioridazine, or ziprasidone; or
  • migraine headache medicine such as sumatriptan or zolmitriptan.

This list is not complete. Other drugs may interact with ondansetron, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Where can I get more information?

Your doctor or pharmacist can provide more information about ondansetron injection.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 4.02. Revision date: 12/5/2012.

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