"The U.S. Food and Drug Administration today expanded the approved use of Stivarga (regorafenib) to treat patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved t"...
The following have been reported as adverse events in clinical trials of patients treated with ondansetron, the active ingredient of ZOFRAN. A causal relationship to therapy with ZOFRAN has been unclear in many cases.
Chemotherapy-Induced Nausea and Vomiting
The adverse events in Table 5 have been reported in ≥ 5% of adult patients receiving a single 24-mg ZOFRAN Tablet in 2 trials. These patients were receiving concurrent highly emetogenic cisplatin-based chemotherapy regimens (cisplatin dose ≥ 50 mg/m ).
Table 5: Principal Adverse Events in US Trials: Single
Day Therapy With 24-mg ZOFRAN Tablets
(Highly Emetogenic Chemotherapy)
|Event||Ondansetron 24 mg q.d.
n = 300
|Ondansetron 8 mg b.i.d.
n = 124
|Ondansetron 32 mg q.d.
n = 117
|Headache||33 (11%)||16 (13%)||17 (15%)|
|Diarrhea||13 (4%)||9 (7%)||3 (3%)|
The adverse events in Table 6 have been reported in ≥ 5% of adults receiving either 8 mg of ZOFRAN Tablets 2 or 3 times a day for 3 days or placebo in 4 trials. These patients were receiving concurrent moderately emetogenic chemotherapy, primarily cyclophosphamide-based regimens.
Table 6: Principal Adverse Events in US Trials: 3 Days
of Therapy With 8-mg ZOFRAN Tablets (Moderately Emetogenic Chemotherapy)
|Event||Ondansetron 8 mg b.i.d.
n = 242
|Ondansetron 8 mg t.i.d.
n = 415
n = 262
|Headache||58 (24%)||113 (27%)||34 (13%)|
|Malaise/fatigue||32 (13%)||37 (9%)||6 (2%)|
|Constipation||22 (9%)||26 (6%)||1 ( < 1%)|
|Diarrhea||15 (6%)||16 (4%)||10 (4%)|
|Dizziness||13 (5%)||18 (4%)||12 (5%)|
Central Nervous System: There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving ondansetron.
Hepatic: In 723 patients receiving cyclophosphamide-based chemotherapy in US clinical trials, AST and/or ALT values have been reported to exceed twice the upper limit of normal in approximately 1% to 2% of patients receiving ZOFRAN Tablets. 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. The role of cancer chemotherapy in these biochemical changes cannot be clearly determined.
There have been reports of liver failure and death in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear.
Integumentary: Rash has occurred in approximately 1% of patients receiving ondansetron.
Other: Rare cases of anaphylaxis, bronchospasm, tachycardia, angina (chest pain), hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures have been reported. Except for bronchospasm and anaphylaxis, the relationship to ZOFRAN was unclear.
Radiation-Induced Nausea and Vomiting
The adverse events reported in patients receiving ZOFRAN Tablets and concurrent radiotherapy were similar to those reported in patients receiving ZOFRAN Tablets and concurrent chemotherapy. The most frequently reported adverse events were headache, constipation, and diarrhea.
Postoperative Nausea and Vomiting
The adverse events in Table 7 have been reported in ≥ 5% of patients receiving ZOFRAN Tablets at a dosage of 16 mg orally in clinical trials. With the exception of headache, rates of these events were not significantly different in the ondansetron and placebo groups. These patients were receiving multiple concomitant perioperative and postoperative medications.
Table 7: Frequency of Adverse Events From Controlled
Studies With ZOFRAN Tablets (Postoperative Nausea and Vomiting)
|Adverse Event||Ondansetron 16 mg
(n = 550)
(n = 531)
|Wound problem||152 (28%)||162 (31%)|
|Drowsiness/sedation||112 (20%)||122 (23%)|
|Headache||49 (9%)||27 (5%)|
|Hypoxia||49 (9%)||35 (7%)|
|Pyrexia||45 (8%)||34 (6%)|
|Dizziness||36 (7%)||34 (6%)|
|Gynecological disorder||36 (7%)||33 (6%)|
|Anxiety/agitation||33 (6%)||29 (5%)|
|Bradycardia||32 (6%)||30 (6%)|
|Shiver(s)||28 (5%)||30 (6%)|
|Urinary retention||28 (5%)||18 (3%)|
|Hypotension||27 (5%)||32 (6%)|
|Pruritus||27 (5%)||20 (4%)|
Preliminary observations in a small number of subjects suggest a higher incidence of headache when ZOFRAN ODT Orally Disintegrating Tablets are taken with water, when compared to without water.
Observed During Clinical Practice
In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of oral formulations of ZOFRAN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ZOFRAN.
Cardiovascular: Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.
General: Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis/anaphylactoid reactions, angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been reported. Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients receiving injectable ondansetron.
Hepatobiliary: Liver enzyme abnormalities
Lower Respiratory: Hiccups
Neurology: Oculogyric crisis, appearing alone, as well as with other dystonic reactions
Special Senses: 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.
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.
Read the Zofran (ondansetron hydrochloride) Side Effects Center for a complete guide to possible side effects
Ondansetron does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver (see CLINICAL PHARMACOLOGY, Pharmacokinetics). 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. On the basis of 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, concomitant use of apomorphine with ondansetron is contraindicated (see CONTRAINDICATIONS).
Phenytoin, Carbamazepine, and Rifampicin
In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampicin), 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.1,3
Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) (see WARNINGS).
Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small studies indicate that ondansetron may be associated with an increase in patient controlled administration of tramadol.4,5
Tumor response to chemotherapy in the P-388 mouse leukemia model is not affected by ondansetron. In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.
In a crossover study in 76 pediatric patients, I.V. ondansetron did not increase blood levels of high-dose methotrexate.
Use In Surgical Patients
The coadministration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.
Read the Zofran Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 11/7/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Zofran Information
Zofran - User Reviews
Zofran User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.