Sancuso · 4.1 Therapeutic indications · 1

HOS-155303 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile 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. Tabulated list of adverse reactions 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. 5 Table 1: Adverse reactions reported for SANCUSO System Organ Class Adverse reaction Frequency Immune system disorder Hypersensitivity reactions Not known Metabolism and nutrition Decreased appetite Uncommon disorders Nervous system disorders Headache Uncommon Dystonia Rare Dyskinesia Rare Serotonin syndrome Unknown Ear and labyrinth disorders Vertigo Uncommon Vascular disorders Flushing Uncommon Gastrointestinal disorders Constipation Common Dry mouth, nausea, retching Uncommon Hepatobiliary disorders Alanine aminotransferase Uncommon increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased Musculoskeletal and connective Arthralgia Uncommon tissue disorders General disorders and Generalised oedema Uncommon administration site conditions Application site irritation*

Auszug; vollständigen Abschnitt im Original lesen.

HOS-155299 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance, to other 5-HT3 receptor antagonists or to any of the excipients listed in section 6.1.

HOS-155298 · has-indication-information · PDF-Seite 2

SANCUSO transdermal patch is indicated in adults for the prevention of nausea and vomiting associated with moderately or highly emetogenic chemotherapy, for a planned duration of 3 to 5 consecutive days, where oral anti-emetic administration is complicated by factors making swallowing difficult (see section 5.1).

HOS-155301 · has-interaction-information · PDF-Seite 4

For serotonergic medicinal products (e.g. SSRIs and SNRIs, buprenorphine, opiods or other serotonergic medicinal products), 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 4 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. Paediatric population Interaction studies have only been performed in adults.

HOS-155302 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are limited amount of data (less than 300 pregnancy outcomes) 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 SANCUSO during pregnancy. Breast-feeding It is unknown whether granisetron or its metabolites are excreted in human milk. Breast-feeding should be discontinued during treatment with SANCUSO. Fertility There are no data on the effect of granisetron on human fertility.

HOS-155300 · has-warning-information · PDF-Seite 3

Application site reactions 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. Gastrointestinal disorders Granisetron may mask a progressive ileus and/or gastric distension caused by an underlying condition. Patients with signs of sub-acute intestinal obstruction should be monitored following its administration, as granisetron may reduce lower bowel motility. Cardiac disorders 5-HT3 receptor antagonists, such as granisetron, may be associated with arrhythmias or ECG abnormalities. This may potentially have clinical significance in patients with pre-existing arrhythmias or cardiac conduction disorders and/or treated with antiarrhythmics or beta blockers. No clinically relevant effects have been observed in clinical studies with SANCUSO. 3 Exposure to sunlight Granisetron may be affected by direct natural or artificial sunlight, see section 5.3 for further information. Patients must 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 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 External heat (for example hot water bottles or heat pads) should be avoided on the area of the transdermal patch. Special populations 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. 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 medicinal products (including selective serotonin reuptake inhibitors (SSRIs), and serotonin noradrenaline reuptake inhibitors (SNRIs). There have also been reports of possible drug-drug interactions between buprenorphine/

Auszug; vollständigen Abschnitt im Original lesen.