Special Warning : אזהרת שימוש

4.4.      Special Warnings and Precautions for Use

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HT3 receptor antagonists.

Respiratory events should be treated symptomatically and clinicians should pay particular attention to them as precursors of hypersensitivity reactions.

Ondansetron prolongs the QT interval in a dose-dependent manner (see section 5.1). In addition, post- marketing cases of Torsade de Pointes have been reported in patients using ondansetron.
Avoid ondansetron in patients with congenital long QT syndrome. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc, including patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation or electrolyte abnormalities.

Myocardial ischemia has been reported in patients treated with ondansetron. In some cases, predominantly during intravenous administration, the symptoms appeared immediately after administration but recovered with prompt treatment. Therefore, caution should be exercised during and after administration of ondansetron.
Hypokalaemia and hypomagnesaemia should be corrected prior to ondansetron administration.
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-HT 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 Ondansetron and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Ondansetron and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Ondansetron is used concomitantly with other serotonergic drugs (see Sections 4.5 and 4.9).

As ondansetron is known to increase large bowel transit time, patients with signs of sub- acute intestinal obstruction should be monitored following administration.

In patients with adenotonsillar surgery prevention of nausea and vomiting with ondansetron may mask occult bleeding. Therefore, such patients should be followed carefully after ondansetron.

Ondansetron Injection contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium- free”.

Paediatric Population:
Paediatric patients receiving ondansetron with hepatotoxic chemotherapeutic agents should be monitored closely for impaired hepatic function.

CINV
When calculating the dose on an mg/kg basis and administering three doses at 4 hour intervals, the total daily dose will be higher than if one single dose of 5mg/m2 followed by an oral dose is given.
The comparative efficacy of these two different dosing regimens has not been investigated in clinical trials.
Cross-trial comparison indicates similar efficacy for both regimens (section 5.1).

Excipient(s) with known effect
This medicine contains less than 1mmol sodium (23 mg) per 2 – 6 ml dose, that is to say essentially ‘sodium-free’. When the dose is greater than 6 ml it cannot be considered ‘sodium-free’ and it should be taken into consideration by patients on a controlled sodium diet. At maximum daily dose (16 ml) this medicine contains 56 mg of sodium. This is equivalent to approximately 2.3% of the recommended maximum daily dietary intake of sodium for an adult.

Effects on Driving