ZUPLENZ SIDE EFFECTS
- Generic Name: ondansetron oral soluble film
- Brand Name: Zuplenz
- Drug Class: Antiemetics, Selective 5-HT3 Antagonist
SIDE EFFECTS
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 N=300 |
Ondansetron 8 mg twice daily N=124 |
Ondansetron 32 mg once daily N=117 |
| 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 cyclophosphamide-based regimens)]
| Adverse Event | Ondansetron 8 mg twice daily N=242 |
Ondansetron 8 mg three times daily N=415 |
Placebo 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%) |
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 N=550 |
Placebo N=531 |
| 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 groups. bPatients were receiving multiple concomitant perioperative and postoperative medications. |
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Postmarketing Experience
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.
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 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
Skin
Urticaria
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.