GRANISETRON Film-coated tablet Ref.[8215] Active ingredients: Granisetron

As granisetron may reduce lower bowel motility, patients with signs of sub-acute intestinal obstruction should be monitored following administration of granisetron.

As for other 5-HT₃ antagonists, ECG changes including QT interval prolongation have been reported with granisetron. In patients with pre-existing arrhythmias or cardiac conduction disorders this might lead to clinical consequences. Therefore caution should be exercised in patients with cardiac co-morbidities, on cardiotoxic chemotherapy and/or with concomitant electrolyte abnormalities (see section 4.5).

Cross-sensitivity between 5-HT₃ antagonists (e.g.dolasetron, ondansetron) has been reported.

Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Serotonin Syndrome

There have been reports of serotonin syndrome with the use of 5-HT₃ antagonists either alone, but mostly in combination with other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRIs), and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised.

Granisetron is essentially ‘sodium free’ as it contains less than 1 mmol sodium (23 mg) per dose (2 mg). To be used with caution in children or in patients on a low sodium diet.

Paediatric population

There is insufficient clinical evidence to recommend administration of these tablets to children.

As for other 5-HT₃ antagonists, cases of ECG modifications including QT prolongation have been reported with granisetron. In patients concurrently treated with medicinal products known to prolong QT interval and/or which are arrhythmogenic, this may lead to clinical consequences (see section 4.4).

In studies in healthy subjects, no evidence of any interaction has been indicated between granisetron and benzodiazepines (lorazepam), neuroleptics (haloperidol) or anti-ulcer medicinal products (cimetidine). Additionally, granisetron has not shown any apparent medicinal product interaction with emetogenic cancer chemotherapies.

No specific interaction studies have been conducted in anaesthetised patients.

Serotonergic medicinal products (e.g. SSRIs and SNRIs): there have been reports of serotonin syndrome following concomitant use of 5-HT₃ antagonists and other serotonergic medicinal products (including SSRIs and SNRIs) (see section 4.4).

Pregnancy

There is limited amount of data from the use of granisetron in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of granisetron during pregnancy.

Breast-feeding

It is unknown whether granisetron or its metabolites are excreted in human milk. As a precautionary measure, breast-feeding should not be advised during treatment with granisetron.

Fertility

In rats, granisetron had no harmful effects on reproductive performance or fertility.

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

Summary of the safety profile

The most frequently reported adverse reactions for granisetron are headache and constipation, which may be transient. ECG changes including QT prolongation have been reported with granisetron (see sections 4.4 and 4.5).

Tabulated list of adverse reactions

The following table of listed adverse reactions is derived from clinical trials and post-marketing data associated with granisetron and other 5-HT₃ antagonists.

Frequency categories are as follows: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000).

Immune system disorders

Uncommon: Hypersensitivity reactions e.g. anaphylaxis, urticaria

Psychiatric disorders

Common: Insomnia

Nervous system disorders

Very common: Headache

Uncommon: Extrapyramidal Reactions, Serotonin Syndrome (see also sections 4.4 and 4.5)

Cardiac disorders

Uncommon: QT prolongation

Gastrointestinal disorders

Very common: Constipation

Common: Diarrhoea

Hepatobiliary disorders

Common: Elevated hepatic transaminases*

Skin and subcutaneous tissue disorders

Uncommon: Rash

* Occurred at a similar frequency in patients receiving comparator therapy

Description of selected adverse reactions

As for other 5-HT₃ antagonists, ECG changes including QT prolongation have been reported with granisetron (see sections 4.4 and 4.5).

As with other 5-HT₃ antagonists, cases of serotonin syndrome (including altered mental status, autonomic dysfunction and neuromuscular abnormalities) have been reported following the concomitant use of granisetron and other serotonergic drugs (see sections 4.4 and 4.5).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Not applicable.