Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Kyowa Kirin Holdings B.V., Bloemlaan 2, 2132NP Hoofddorp, The Netherlands, Tel: +31 (0) 237200822
Hypersensitivity to the active substance, to other 5-HT3 receptor antagonists or to any of the excipients listed in section 6.1.
In clinical trials with SANCUSO, application site reactions were reported which were generally mild in intensity and did not lead to discontinuation of use. If severe reactions, or a generalised skin reaction occur (e.g. allergic rash, including erythematous, macular, papular rash or pruritus), the transdermal patch must be removed.
As granisetron may reduce lower bowel motility, patients with signs of sub-acute intestinal obstruction should be monitored following its administration.
5-HT3 receptor antagonists, such as granisetron, may be associated with arrhythmias or ECG abnormalities. This potentially may have clinical significance in patients with pre-existing arrhythmias or cardiac conduction disorders or patients who are being treated with antiarrhythmics or beta-blockers. No clinically relevant effects have been observed in clinical studies with SANCUSO.
Granisetron may be affected by direct natural or artificial sunlight, see section 5.3 for further information. Patients must be advised to cover the transdermal patch application site, e.g. with clothing, if there is a risk of exposure to sunlight throughout the period of wear and for 10 days following its removal.
Showering or washing normally can be continued while wearing SANCUSO. Activities such as swimming, strenuous exercise or using a sauna should be avoided.
External heat (for example hot water bottles or heat pads) should be avoided on the area of the transdermal patch.
No dose adjustments are necessary for the elderly or patients with renal or hepatic impairment. Although no evidence of an increased incidence of adverse reactions have been observed in patients with renal or hepatic impairment receiving granisetron orally and intravenously, based on granisetron pharmacokinetics, a degree of caution must be exercised in this population.
There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone, but mostly in combination with other serotonergic medicinal products (including selective serotonin reuptake inhibitors (SSRIs), and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised.
For 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).
Co-administration of intravenous 5-HT3 receptor antagonists with oral paracetamol in human subjects has been reported to result in a block in the analgesic effect via a pharmacodynamic mechanism.
As granisetron is metabolised by hepatic cytochrome P450 active substance-metabolising enzymes (CYP1A1 and CYP3A4), inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of granisetron.
In human subjects, hepatic enzyme induction by phenobarbital has led to an increase in total plasma clearance (approximately 25%) following intravenous administration of granisetron.
In vitro studies have shown that ketoconazole may inhibit the metabolism of granisetron via the cytochrome P450 3A isoenzyme family. The clinical significance of this is unknown.
In vitro studies using human microsomes indicate that granisetron neither stimulates nor inhibits the cytochrome P450 enzyme system.
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).
No clinically relevant interactions between SANCUSO and emetogenic cancer chemotherapies have been seen. Furthermore, no interaction has been observed between granisetron and emetogenic cancer therapies. In agreement with these data, no clinically relevant interactions have been reported in clinical studies with SANCUSO. In clinical interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of granisetron.
Interaction studies have only been performed in adults.
There are no data on 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 SANCUSO during pregnancy.
It is unknown whether granisetron or its metabolites are excreted in human milk. Breast-feeding should be discontinued during treatment with SANCUSO.
There are no data on the effect of granisetron on human fertility. Fertility was unaffected following granisetron treatment in rats.
SANCUSO has no or negligible influence on the ability to drive and use machines.
The safety profile of SANCUSO is derived from controlled clinical trials and from post-marketing experience. The most commonly reported adverse reaction in clinical studies was constipation, occurring in approximately 8.7% of patients. The majority of adverse reactions were mild or moderate in severity.
Adverse reactions from clinical studies and spontaneous reports with SANCUSO are listed in the table below.
Within the system organ class, the adverse reactions are listed by frequency using the following convention: 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) and not known (cannot be estimated from the available data).
Adverse reactions are presented in order of decreasing seriousness within each frequency grouping.
Table 1. Adverse reactions reported for SANCUSO:
Not known: Hypersensitivity reactions
Uncommon: Decreased appetite
Uncommon: Headache
Rare: Dystonia, Dyskinesia
Uncommon: Vertigo
Uncommon: Flushing
Common: Constipation
Uncommon: Dry mouth, nausea, retching
Uncommon: Alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased
Uncommon: Application site irritation
Not known: Application site reactions (application site pain, application site pruritus, application site erythema, application site rash, application site irritation)*
Uncommon: Arthralgia
Uncommon: Generalised oedema
Patients who are being treated with moderately or highly emetogenic chemotherapy may still experience vomiting despite treatment with antiemetic therapy, including SANCUSO.
Class effects for granisetron seen with other formulations (oral and intravenous) include the following:
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 national reporting system listed in Appendix V.
Not applicable.
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