GRANISETRON Concentrate for solution for injection or infusion Ref.[8216] Active ingredients: Granisetron

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

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.

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.

This medicine contains:

• a maximum of 27.7 mg (or 1.2 mmol) sodium per 1 ml ampoule, equivalent to 1.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
• a maximum of 83.1 mg (or 3.6 mmol) sodium per 3 ml ampoule, equivalent to 4.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

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 humans, hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of granisetron of approximately 25%.

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.

Breastfeeding

It is unknown whether granisetron or its metabolites are excreted in human milk. As a precautionary measure, breastfeeding 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 or to 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 summary 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

Cardiac disorders

Uncommon: QT interval prolonged

Gastrointestinal disorders

Very common: Constipation

Common: Diarrhoea

Hepatobiliary disorders

Common: Transaminases increased*

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).

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.