6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
- QT Prolongation [see Warnings and Precautions (5.2)]
- Serotonin Syndrome [see Warnings and Precautions (5.3)]
- Myocardial Ischemia [see Warnings and Precautions (5.4)]
- Masking of Progressive Ileus and Gastric Distension [see Warnings and Precautions (5.5)]
6.1 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 with 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 ondansetron across a range of dosages. A causal relationship to therapy with ondansetron was unclear in many cases.
Chemotherapy-Induced Nausea and Vomiting
|Number of Adult Patients With Reaction|
|Adverse Reaction||Ondansetron Injection|
0.15 mg/kg × 3
(n = 419)
(n = 156)
(n = 34)
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 Ondansetron Injection, and rare cases of grand mal seizure.
Other: Rare cases of hypokalemia have been reported.
Postoperative Nausea and/or Vomiting
The adverse reactions in Table 3 have been reported in ≥ 2% of adults receiving ondansetron at a dosage of 4 mg intravenous over 2 to 5 minutes in clinical trials.
|Adverse Reaction*,†||Ondansetron Injection|
4 mg Intravenous
(n = 547)
(n = 547)
|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%)|
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 ondansetron (2%) compared with placebo (< 1%) in the 1-month to 24-month age-group. These patients were receiving multiple concomitant perioperative and postoperative medications.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval 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.
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 (5.2)].
Myocardial ischemia was reported predominately with intravenous administration [see Warnings and Precautions (5.4)].
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.
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.
Oculogyric crisis, appearing alone, as well as with other dystonic reactions. Transient dizziness during or shortly after intravenous infusion.
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, has also been reported.