Source: European Medicines Agency (EU) Revision Year: 2018 Publisher: Helsinn Birex Pharmaceuticals Ltd., Damastown, Mulhuddart, Dublin 15, Ireland
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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.
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodiumfree’.
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.
In preclinical studies, palonosetron did not inhibit the antitumour activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C).
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.
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).
Palonosetron has been administered safely with corticosteroids.
There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).
Palonosetron has been administered safely with analgesics, antiemetic/antinauseants, antispasmodics and anticholinergic medicinal products.
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.
As there are no data concerning palonosetron excretion in breast milk, breast-feeding should be discontinued during therapy.
There are no data concerning the effect of palonosetron on fertility.
No studies on the effects on the ability to drive and use machines have been performed. Since palonosetron may induce dizziness, somnolence or fatigue, patients should be cautioned when driving or operating machines.
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.
Very rare°: Hypersensitivity, anaphylaxis, anaphylactic/anaphylactoid reactions and shock
Uncommon: Hyperkalaemia, metabolic disorders, hypocalcaemia, hypokalaemia, anorexia, hyperglycaemia, appetite decreased
Uncommon: Anxiety, euphoric mood
Common: Headache, Dizziness
Uncommon: Somnolence, insomnia, paraesthesia, hypersomnia, peripheral sensory neuropathy
Uncommon: Eye irritation, amblyopia
Uncommon: Motion sickness, tinnitus
Uncommon: Tachycardia, bradycardia, extrasystoles, myocardial ischaemia, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles
Uncommon: Hypotension, hypertension, vein discolouration, vein distended
Uncommon: Hiccups
Common: Constipation, Diarrhoea
Uncommon: Dyspepsia, abdominal pain, abdominal pain upper, dry mouth, flatulence
Uncommon: Hyperbilirubinaemia
Uncommon: Dermatitis allergic, pruritic rash
Uncommon: Arthralgia
Uncommon: Urinary retention, glycosuria
Uncommon: Asthenia, pyrexia, fatigue, feeling hot, influenza like illness
Very rare°: Injection site reaction*
Uncommon: Elevated transaminases-, electrocardiogram QT prolonged
° From post-marketing experience
* Includes the following: burning, induration, discomfort and pain
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%.
Common: Headache
Uncommon: Dizziness, dyskinesia
Uncommon: Electrocardiogram QT prolonged conduction disorder, sinus tachycardia
Uncommon: Cough, dyspnoea, epistaxis
Uncommon: Dermatitis allergic, pruritus, skin disorder, urticaria
Uncommon: Pyrexia, infusion site pain, infusion site reaction, pain
Adverse reactions were evaluated in paediatric patients receiving palonosetron for up to 4 chemotherapy cycles.
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.
This medicinal product must not be mixed with other medicinal products.
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