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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 events have been reported in clinical trials of patients treated with ondansetron, the active ingredient of ZUPLENZ. A causal relationship to therapy with ondansetron was unclear in many cases.
Chemotherapy-Induced Nausea and Vomiting
Table 1: Adverse Events Reported in ≥ 5% of Adult
Patients After Single Day Therapy Ondansetron HCl Tablets [Highly Emetogenic
Chemotherapy (cisplatin dose ≥ 50 mg/m²)]
|Adverse Event||Ondansetron 24 mg once daily
|Ondansetron 8 mg twice daily
|Ondansetron 32 mg once daily
|Headache||33 (11%)||16 (13%)||17 (15%)|
|Diarrhea||13 (4%)||9 (7%)||3 (3%)|
Table 2: Adverse Events
Reported in ≥ 5% of Adult Patients After Three Days of Therapy With
Ondansetron HCl Tablets [Moderately Emetogenic Chemotherapy (primarily
|Adverse Event||Ondansetron 8 mg twice daily
|Ondansetron 8 mg three times daily
|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%)|
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 ondansetron HCl 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 ondansetron was unclear.
Radiation-Induced Nausea and Vomiting
The adverse events reported in patients receiving ondansetron HCl tablets and concurrent radiotherapy were similar to those reported in patients receiving ondansetron HCl tablets and concurrent chemotherapy. The most frequently reported adverse events were headache, constipation, and diarrhea.
Postoperative Nausea and Vomiting
Table 3: Adverse Events
Reported in ≥ 5% of Adult Patients After Single Dose Therapy With
Ondansetron HCl Tablets
|Adverse Event a,b||Ondansetron 16 mg
|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%)|
|Urinary retention||28 (5%)||18 (3%)|
|Pruritus||27 (5%)||20 (4%)|
|aAdverse Events: With the exception of headache, rates of
these events were not significantly different in the ondansetron and placebo
bPatients were receiving multiple concomitant perioperative and postoperative medications.
In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of oral formulations of ondansetron. Because these events are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ondansetron.
Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.
Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis 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.
Liver enzyme abnormalities
Oculogyric crisis, appearing alone, as well as with other dystonic reactions
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.
Read the Zuplenz (ondansetron oral soluble film) 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.
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, 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-HT 3 receptor antagoinists and other serotonergic drugs, including selective serotonin reuptake inhibitor (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) [see WARNINGS AND PRECAUTIONS].
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 in the studies self-administered tramadol more frequently, leading to an increased cumulative dose in patient controlled administration (PCA) of tramadol.4,5
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 co-administration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.
Bioavailability of ondansetron is unaffected by antacids
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.
1. Britto MR, Hussey EK, Mydlow P, et al. Effect of enzyme inducers on ondansetron (OND) metabolism in humans. Clin Pharmacol Ther. 1997;61:228.
2. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Brit J Surg. 1973;60:646-649.
3. Villikka K, Kivisto KT, Neuvonen PJ. The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999;65:377-381.
4. De Witte JL, Schoenmaekers B, Sessler DI, et al. Anesth Analg. 2001;92:1319-1321.
5. Arcioni R, della Rocca M, Romaṇ R, et al. Anesth Analg. 2002;94:1553-1557.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 10/1/2014
Additional Zuplenz Information
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