PALONOSETRON HYDROCHLORIDE

Palonosetron should be used only before chemotherapy administration. This medicinal product should be administered by a healthcare professional under appropriate medical supervision Posology Adults 250 micrograms palonosetron administered as a single intravenous bolus approximately 30 minutes before the start of chemotherapy.

Palonosetron should be injected over 30seconds. The efficacy of palonosetron in the prevention of nausea and vomiting induced by highly emetogenic chemotherapy may be enhanced by the addition of a corticosteroid administered prior to chemotherapy Elderly population No dose adjustment is necessary for the elderly.

Paediatric population Children and Adolescents (aged 1 month to 17 years): 20 micrograms/kg (the maximum total dose should not exceed 1500 micrograms) palonosetron administered as a single 15 minute intravenous infusion beginning approximately 30 minutes before the start of chemotherapy.

The safety and efficacy of palonosetron in children aged less than 1 month have not been established. No data are available. There are limited data on the use of palonosetron in the prevention of nausea and vomiting in children under 2 years of age.

Hepatic impairment No dose adjustment is necessary for patients with impaired hepatic function. Renal impairment No dose adjustment is necessary for patients with impaired renal function. No data are available for patients with end stage renal disease undergoing haemodialysis.

Method of administration For intravenous use.

In clinical studies at a dose of 250 micrograms (total 633 patients) the most frequently observed adverse reactions, at least possibly related to palonosetron, were headache (9 %) and constipation (5 %). These are classified as common (≥1/100 to<1/10), uncommon (≥1/1000 to<1/100), very rare (<1/10000) adverse reactions were reported post-marketing.

Within each frequency grouping, adverse reactions are presented below in order of decreasing seriousness. MedDRAOrgan Systemclasses Common ARs (≥1/100 to<1/10) Uncommon ARs (≥1/1000 to <1/100) Very rare ARs° ImmuneSystem disorders Hypersensitivity, anaphylaxis, anaphylactic/ anaphylactoid reactions and shock Metabolism andnutritiondisorders Hyperkalaemia, metabolic disorders, hypocalcaemia, hypokalaemia, anorexia, hyperglycaemia, appetite decreased Psychiatricdisorders Anxiety, euphoric mood Nervoussystem disorders Headache Dizziness Somnolence, insomnia, paraesthesia, hypersomnia, peripheral sensory neuropathy Eyedisorders Eye irritation, amblyopia Ear andlabyrinthdisorders Motion sickness, tinnitus Cardiac disorders Tachycardia, bradycardia, extrasystoles, myocardial ischaemia, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles Vasculardisorders Hypotension, hypertension, vein discolouration, vein distended Respiratory,thoracic andmediastinaldisorders Hiccups Gastrointestinal disorders Constipation Diarrhoea Dyspepsia, abdominal pain, abdominal pain upper, dry mouth, flatulence Hepatobiliary disorders Hyperbilirubinaemia Skin andsubcutaneoustissue disorders Dermatitis allergic, pruritic rash Musculoskeletaland connectivetissue disorders Arthralgia Renal andurinary Disorders Urinary retention, glycosuria Generaldisorders andadministrationsite conditions Asthenia, pyrexia, fatigue, feeling hot, influenza like illness Injection site reaction* Investigations Elevated transaminases-, electrocardiogram QT prolonged ° From post-marketing experience * Includes the following: burning, induration, discomfort and pain Paediatric population In paediatric clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 402 patients received a single dose of palonosetron (3, 10 or 20 mcg/kg).

The following common or uncommon adverse reactions were reported for palonosetron, none were reported at a frequency of >1%. System organ class Common ARs (≥1/100 to <1/10) Uncommon ARs (≥1/1000 to <1/100) Nervous system disorders Headache Dizziness, dyskinesia Cardiac disorders Electrocardiogram QT prolonged conduction disorder, sinus tachycardia Respiratory, thoracic and mediastinal disorders Cough, dyspnoea, epistaxis Skin and subcutaneous tissue disorders Dermatitis allergic, pruritus, skin disorder, urticarial General disorders and administration site conditions Pyrexia, infusion site pain, infusion site reaction, pain Adverse reactions were evaluated in paediatric patients receiving palonosetron for up to 4 chemotherapy cycles.

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. uk/yellowcard.

As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of sub-acute intestinal obstruction should be monitored following administration. Two cases of constipation with fecal impaction requiring hospitalization 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. 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. Palonosetron should not be used to prevent or treat nausea and vomiting in the days following chemotherapy if not associated with another chemotherapy administration.

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