"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists. ZUPLENZ (ondansetron) oral soluble film should be discontinued immediately at the first sign of hypersensitivity.
ECG changes including QT interval prolongation have been seen in patients receiving ondansetron. In addition, post-marketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ZUPLENZ 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.
The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of ondansetron alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post anesthesia care unit or an infusion center.
Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Zuplenz and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Zuplenz and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Zuplenz is used concomitantly with other serotonergic drugs [see DRUG INTERACTIONS, OVERDOSAGE, PATIENT INFORMATION].
Masking Of Progressive Ileus And/Or Gastric Distension
Effect On Peristalsis
Patient Counseling Information
See FDA-Approved Patient Labeling
Advise patients to carefully read the “PATIENT INFORMATION” and “Instructions for Use” accompanying each package of ZUPLENZ (ondansetron) oral soluble film.
Inform patients that ZUPLENZ may cause serious cardiac arrhythmias such as QT prolongation. Instruct patients 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.
Inform patients 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 hypomagnesaemia
ZUPLENZ should be avoided in these patients, since they may be more at risk for cardiac arrhythmias such as QT prolongation and Torsade de Pointes.
- Advise patients of the possibility of serotonin syndrome with concomitant use of Zuplenz and another serotonergic agent such as medications to treat depression and migraines. Advise patients to seek immediate medical attention if the following symptoms occur: changes in mental status, autonomic instability, neuromuscular symptoms with or without gastrointestinal symptoms.
Inform patients that ZUPLENZ film may cause headache, malaise/fatigue, constipation, and diarrhea. The patient should report the use of all medications, especially apomorphine or any drug of the 5HT3 antagonist class, to their health care provider. Concomitant use of apomorphine and ondansetron may cause a significant drop in blood pressure and loss of consciousness.
Inform patients that ZUPLENZ may cause hypersensitivity reactions, some as severe as anaphylaxis and bronchospasm. The patient should report any hypersensitivity reactions to this and other 5-HT3 receptor antagonists to their health care provider.
Instruct patients on how to use ZUPLENZ films: The patient should keep the film in the pouch until ready to use and not to chew or swallow the film. With dry hands, the patient should fold the pouch along the dotted line to expose the tear notch. While still folded, the patient should tear the pouch carefully along the edge and remove the ZUPLENZ oral soluble film from the pouch. The patient should immediately place the film on top of the tongue where it dissolves in 4 to 20 seconds, then swallow with saliva. Once the film dissolves, the patient may swallow liquid but it is not required. The patient should wash his hands after taking ZUPLENZ.
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 mg/kg/day and 30 mg/kg/day, respectively (approximately 5 and 8 times the human dose of 16 mg/day, based on body surface area). Ondansetron was not mutagenic in standard tests for mutagenicity. Oral administration of ondansetron up to 15 mg/kg/day (approximately 8 times the human dose of 16 mg/day, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.
Use In Specific Populations
Pregnancy Category B. Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg/day, respectively (approximately 8 and 30 times the human dose of 16 mg/day, 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, ZUPLENZ (ondansetron) oral soluble film should be used during pregnancy only if clearly needed.
Ondansetron is excreted in the 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 ZUPLENZ oral soluble film is administered to a nursing woman.
Little information is available about dosage in pediatric patients less than 4 years of age. For dosage recommendations in the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy for patients 4 years of age and older [see DOSAGE AND ADMINISTRATION]. The safety and effectiveness in pediatric patients have not been established for the following indications: prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, prevention of nausea and vomiting associated with radiotherapy, and prevention of postoperative nausea and/or vomiting.
Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US-and foreign-controlled clinical trials, for which there were subgroup analyses, 938 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].
The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.
In patients with severe hepatic impairment (Child-Pugh score of 10 or greater)2, 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.
Last reviewed on RxList: 10/1/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Zuplenz Information
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