Ondansetron Other names: Ondasetron

Caution should be exercised when ondansetron is co-administered with drugs that prolong the QT interval and/or cause electrolyte abnormalities. Use of ondansetron with QT prolonging drugs may result in additional QT prolongation. Concomitant use of ondansetron with cardiotoxic drugs (e.g. anthracyclines (such as doxorubicin, daunorubicin) or trastuzumab), antibiotics (such as erythromycin), antifungals (such as ketoconazole), antiarrhythmics (such as amiodarone) and beta blockers (such as atenolol or timolol) may increase the risk of arrhythmias.

There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of ondansetron and other serotonergic drugs (including SSRIs and SNRIs).

In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine and rifampicin), the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.

Clearance of ondansetron is significantly reduced and serum half life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg should not be exceeded and therefore parenteral or oral administration is recommended.

Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg should not be exceeded and therefore parenteral or oral administration is recommended.

Concomitant use of ondansetron with cardiotoxic drugs (e.g. anthracyclines (such as doxorubicin, daunorubicin) or trastuzumab), antibiotics (such as erythromycin), antifungals (such as ketoconazole), antiarrhythmics (such as amiodarone) and beta blockers (such as atenolol or timolol) may increase the risk of arrhythmias.

Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.

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

Ondansetron prolongs the QT interval in a dose-dependent manner. In addition, post-marketing cases of Torsades de Pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital 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.

The safety of ondansetron for use in human pregnancy has not been established. Evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to the development of the embryo, or foetus, the course of gestation and peri- and post-natal development.

However as animal studies are not always predictive of human response the use of ondansetron in pregnancy is not recommended.

Tests have shown that ondansetron passes into the milk of lactating animals. It is therefore recommended that mothers receiving Ondansetron should not breast-feed their babies.

Fertility

There is no information on the effects of ondansetron on human fertility.

Ondansetron has no or negligible influence on the ability to drive and use machines.

In psychomotor testing ondansetron does not impair performance nor cause sedation. No detrimental effects on such activities are predicted from the pharmacology of ondansetron.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000) and very rare (<1/10,000). Very common, common and uncommon events were generally determined from clinical trial data. The incidence in placebo was taken into account. Rare and very rare events were generally determined from post-marketing spontaneous data.

The following frequencies are estimated at the standard recommended doses of ondansetron.

Immune system disorders

Rare: Immediate hypersensitivity reactions sometimes severe, including anaphylaxis.

Nervous system disorders

Very Common: Headache

Uncommon: Seizures, movement disorders including extrapyramidal reactions such as dystonic reactions, oculogyric crisis and dyskinesia¹

Rare: Dizziness during rapid IV administration

Eye disorders

Rare: Transient visual disturbances (e.g. blurred vision) predominantly during IV administration

Very rare: Transient blindness predominantly during intravenous administration²

Cardiac disorders

Uncommon: Arrhythmias, chest pain with or without ST segment depression, bradycardia

Rare: QTc prolongation (including Torsades de Pointes)

Vascular disorders

Common: Sensation of warmth or flushing

Uncommon: Hypotension

Respiratory, thoracic and mediastinal disorders

Uncommon: Hiccups

Gastrointestinal disorders

Common: Constipation

Hepatobiliary disorders

Uncommon: Asymptomatic increases in liver function tests³

General disorders and administration site conditions

Common: Local IV injection site reactions

¹ Observed without definitive evidence of persistent clinical sequelae.
² The majority of the blindness cases reported resolved within 20 minutes. Most patients had received chemotherapeutic agents, which included cisplatin. Some cases of transient blindness were reported as cortical in origin.
³ These events were observed commonly in patients receiving chemotherapy with cisplatin.

Paediatric population

The adverse event profiles in children and adolescents were comparable to that seen in adults.