PALONOSETRON

Palonosetron Fresenius Kabi 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 Fresenius Kabi should be injected over 30 seconds. The efficacy of Palonosetron Fresenius Kabi 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 people No dose adjustment is necessary for the elderly. Paediatric population Palonosetron Fresenius Kabi in pre-filled syringe is not recommended for use in children and adolescents. For this population Palonosetron Fresenius Kabi in glass vials can be used.

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. 6

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 %). In the clinical studies the following adverse reactions (ARs) 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) adverse reactions were reported post-marketing. Within each frequency grouping, adverse reactions are presented below in order of decreasing seriousness.

System organ class Common ARs (≥1/100 to<1/10) Uncommon ARs (≥1/1,000 to <1/100) Very rare ARs° (<1/10,000) Immune system disorders Hypersensitivity, anaphylaxis, anaphylactic/ anaphylactoid reactions and shock Metabolism and nutrition disorders Hyperkalaemia, 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 ° 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).

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. 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.

23% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

1.