PALONOSETRON ACCORD

Palonosetron Accord 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 Accord should be injected over 30 seconds. 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. 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. Paediatric population Children and adolescents (aged 1 month to 17 years): 20 micrograms/kg (the maximum total dose should not exceed 1,500 micrograms) palonosetron administered as a single 15 minutes 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. These are limited data on the use of palonosetron in the prevention of nausea and vomiting in children under 2 years of age.

Method of administration For intravenous use.

Summary of the safety profile 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 palonosetron, were headache (9 %) and constipation (5 %).

Tabulated list of adverse reactions In the clinical studies the following adverse drug reactions (ADRs) were observed as possibly or probably related to palonosetron. These were classified as common (≥1/100 to <1/10) or uncommon (≥1/1,000 to <1/100).

Very rare (<1/10,000) ADRs were reported post-marketing. Within each frequency grouping, adverse reactions are presented below in order of decreasing seriousness. System organ class Common ADRs (≥1/100 to<1/10) Uncommon ADRs (≥1/1,000 to <1/100) Very rare ADRs (<1/10,000) Immune system disorders Hypersensitivity, anaphylaxis, anaphylactic/ anaphylactoid reactions and shock Metabolism and Hyperkalaemia, nutrition disorders metabolic disorders, hypocalcaemia, hypokalaemia, anorexia, hyperglycaemia, appetite decreased Psychiatric disorders Anxiety, euphoric mood Nervous system disorders Headache, Dizziness Somnolence, insomnia, 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 tachycardia, sinus arrhythmia, supraventricular extrasystoles Vascular disorders Hypotension, hypertension, vein discolouration, vein distended Respiratory, thoracic and mediastinal disorders Hiccups Gastrointestinal disorders Constipation diarrhoea Dyspepsia, abdominal pain, abdominal pain upper, dry mouth, flatulence Hepatobiliary disorders Hyperbilirubinaemia Skin and subcutaneous tissue disorders Dermatitis allergic, pruritic rash Musculoskeletal and connective tissue disorders Arthralgia Renal and urinary disorders Urinary retention, glycosuria General disorders and administration site conditions Asthenia, pyrexia, fatigue, feeling hot, influenza like illness Injection site reaction* Investigations Elevated transaminases-, electrocardiogram QT prolonged * 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).

QT prolongation 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. Interference with serotonergic medicinal products 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. Other 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. Palonosetron Accord should not be used to prevent or treat nausea and vomiting in the days following chemotherapy if not associated with another chemotherapy administration.

Excipients This medicinal product contains less than 1 mmol sodium (23 mg) per vial that is to say essentially ‘sodium- free’.

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