Aloxi · 4.4 Special warnings and precautions for use · 2

HOS-093892 · has-adverse-reaction-information · PDF-Seite 18

In clinical studies at a dose of 500 micrograms (total 161 patients) the most frequently observed adverse reaction, at least possibly related to Aloxi, was headache (3.7 %). 18 In the clinical studies the following adverse reactions (ARs) were observed as possibly or probably related to Aloxi. These were classified as common (≥1/100 to <1/10) or uncommon (≥1/1,000 to <1/100). System Organ Class Common ARs Uncommon ARs Psychiatric disorders Insomnia Nervous system disorders Headache Eye disorders Eye swelling Cardiac disorders Atrioventricular block first degree, atrioventricular block second degree Respiratory, thoracic and mediastinal Dyspnoea disorders Gastrointestinal disorders Constipation, nausea Musculoskeletal and connective tissue Myalgia disorders Investigations Blood bilirubin increased In post marketing very rare cases (<1/10,000) of hypersensitivity reactions occurred with palonosetron solution for injection for intravenous use. 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 national reporting system listed in Appendix V.

HOS-093886 · has-adverse-reaction-information · PDF-Seite 5

In clinical studies in adults at a dose of 250 micrograms (total 633 patients) the most frequently observed adverse reactions, at least possibly related to Aloxi, were headache (9 %) and constipation (5 %). In the clinical studies the following adverse reactions (ARs) were observed as possibly or probably related to Aloxi. These were classified as common (≥1/100 to <1/10) or uncommon (≥1/1,000 to <1/100). Very rare (<1/10,000) adverse reactions were reported post-marketing. Within each frequency grouping, adverse reactions are presented below in order of decreasing seriousness. 5 System organ class Common ARs Uncommon ARs Very rare ARs° (≥1/100 to<1/10) (≥1/1,000 to <1/100) (<1/10,000) Immune system disorders Hypersensitivity, anaphylaxis, anaphylactic/ anaphylactoid reactions and shock Metabolism and nutrition Hyperkalaemia, metabolic disorders disorders, hypocalcaemia, hypokalaemia, anorexia, hyperglycaemia, appetite decreased Psychiatric disorders Anxiety, euphoric mood Nervous system disorders Headache Somnolence, insomnia, Dizziness paraesthesia, hypersomnia, peripheral sensory neuropathy Eye disorders Eye irritation, amblyopia Ear and labyrinth disorders Motion sickness, tinnitus Cardiac disorders Tachycardia, bradycardia, extrasystoles, myocardial ischaemia, sinus

Auszug; vollständigen Abschnitt im Original lesen.

HOS-093882 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-093888 · has-contraindication-information · PDF-Seite 17

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-093887 · has-indication-information · PDF-Seite 16

Aloxi is indicated in adults for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

HOS-093881 · has-indication-information · PDF-Seite 2

Aloxi is indicated in adults for: • the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy, • the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. Aloxi is indicated in paediatric patients 1 month of age and older for: • the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

HOS-093884 · has-interaction-information · PDF-Seite 4

Palonosetron is mainly metabolised by CYP2D6, with minor contribution by CYP3A4 and CYP1A2 isoenzymes. Based on in vitro studies, palonosetron does not inhibit or induce cytochrome P450 isoenzyme at clinically relevant concentrations. Chemotherapeutic agents In preclinical studies, palonosetron did not inhibit the antitumour activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C). Metoclopramide In a clinical study, no significant pharmacokinetic interaction was shown between a single intravenous dose of palonosetron and steady state concentration of oral metoclopramide, which is a CYP2D6 inhibitor. CYP2D6 inducers and inhibitors In a population pharmacokinetic analysis, it has been shown that there was no significant effect on palonosetron clearance when co-administered with CYP2D6 inducers (dexamethasone and rifampicin) and inhibitors (including amiodarone, celecoxib, chlorpromazine, cimetidine, doxorubicin, fluoxetine, haloperidol, paroxetine, quinidine, ranitidine, ritonavir, sertraline or terbinafine). Corticosteroids Palonosetron has been administered safely with corticosteroids. Serotonergic Drugs (e.g. SSRIs and SNRIs) There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs). Other medicinal products Palonosetron has been administered safely with analgesics, antiemetic/antinauseants, antispasmodics and anticholinergic medicinal products.

HOS-093890 · has-interaction-information · PDF-Seite 17

Palonosetron is mainly metabolised by CYP2D6, with minor contribution by CYP3A4 and CYP1A2 isoenzymes. Based on in vitro studies, palonosetron does not inhibit or induce cytochrome P450 isoenzyme at clinically relevant concentrations. Chemotherapeutic medicinal products U U In preclinical studies, palonosetron did not inhibit the antitumour activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C). 17 Metoclopramide U U In a clinical study, no significant pharmacokinetic interaction was shown between a single intravenous dose of palonosetron and steady state concentration of oral metoclopramide, which is a CYP2D6 inhibitor. CYP2D6 inducers and inhibitors U U In a population pharmacokinetic analysis, it has been shown that there was no significant effect on palonosetron clearance when co-administered with CYP2D6 inducers (dexamethasone and rifampicin) and inhibitors (including amiodarone, celecoxib, chlorpromazine, cimetidine, doxorubicin, fluoxetine, haloperidol, paroxetine, quinidine, ranitidine, ritonavir, sertraline or terbinafine). Corticosteroids U U Palonosetron has been administered safely with corticosteroids. Serotonergic Drugs (e.g. SSRIs and SNRIs) There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs). Other medicinal products U U Palonosetron has been administered safely with analgesics, antiemetic/antinauseants, antispasmodics and anticholinergic medicinal products.

HOS-093885 · has-pregnancy-information · PDF-Seite 4

Pregnancy For Palonosetron no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Only limited data from animal studies are available regarding the placental transfer (see section 5.3). There is no experience of palonosetron in human pregnancy. Therefore, palonosetron should not be used in pregnant women unless it is considered essential by the physician. Breast-feeding As there are no data concerning palonosetron excretion in breast milk, breast-feeding should be discontinued during therapy. Fertility There are no data concerning the effect of palonosetron on fertility. 4

HOS-093891 · has-pregnancy-information · PDF-Seite 18

Pregnancy For Palonosetron, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Only limited data from animal studies are available regarding the placental transfer (see section 5.3). There is no experience of palonosetron in human pregnancy so palonosetron should not be used in pregnant women unless it is considered essential by the physician. Breast-feeding As there are no data concerning palonosetron excretion in breast milk, breast-feeding should be discontinued during therapy. Fertility There are no data concerning the effect of palonosetron on fertility.

HOS-093883 · has-warning-information · PDF-Seite 3

As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration. Two cases of constipation with faecal impaction requiring hospitalisation have been reported in association with palonosetron 750 micrograms. At all dose levels tested, palonosetron did not induce clinically relevant prolongation of the QTc interval. A specific thorough QT/QTc study was conducted in healthy volunteers for definitive data demonstrating the effect of palonosetron on QT/QTc (see section 5.1). However, as for other 5-HT3 antagonists, caution should be exercised in the use of palonosetron in patients who have or are likely to develop prolongation of the QT interval. These conditions include patients with a personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, bradyarrhythmias, conduction disturbances and in patients taking anti-arrhythmic agents or other medicinal products that lead to QT prolongation or electrolyte abnormalities. Hypokalemia and hypomagnesemia should be corrected prior to 5-HT3-antagonist administration. There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised. Aloxi should not be used to prevent or treat nausea and vomiting in the days following chemotherapy if not associated with another chemotherapy administration. 3 This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium- free’.

HOS-093889 · has-warning-information · PDF-Seite 17

As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration. Two cases of constipation with faecal impaction requiring hospitalisation have been reported in association with palonosetron 750 micrograms. At all dose levels tested, palonosetron did not induce clinically relevant prolongation of the QT corrected (QTc) interval. A specific thorough QT/QTc study was conducted in healthy volunteers for definitive data demonstrating the effect of palonosetron on QT/QTc. (see section 5.1). However, as for other 5-HT3 antagonists, caution should be exercised in the use of palonosetron in patients who have or are likely to develop prolongation of the QT interval. These conditions include patients with a personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, bradyarrhythmias, conduction disturbances and in patients taking anti-arrhythmic agents or other medicinal products that lead to QT prolongation or electrolyte abnormalities. Hypokalemia and hypomagnesemia should be corrected prior to 5-HT3-antagonist administration. There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised. Aloxi should not be used to prevent or treat nausea and vomiting in the days following chemotherapy if not associated with another chemotherapy administration. Aloxi contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicinal product. Aloxi capsules may also contain a trace of lecithin derived from soya. Therefore, patients with known hypersensitivity to peanut or soya, should be monitored closely for signs of an allergic reaction.