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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
n = 156
n = 34
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
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.
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.
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
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.
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].
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.
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.
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.
Last reviewed on RxList: 12/23/2013
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