Source: Health Products Regulatory Authority (ZA) Revision Year: 2012 Publisher: Pfizer Laboratories (Pty) Ltd, 85 Bute Lane, Sandton, 2196
Hypersensitivity to the active substance, palonosetron.
Hypersensitivity to any excipients listed under ‘Composition’.
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 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.
However, as for other 5-HT3 antagonists, caution should be exercised in the concomitant use of palonosetron with medicinal products that increase the QT interval or in patients who have or are likely to develop prolongation of the QT interval.
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 isoenzymes at clinically relevant concentrations.
In preclinical studies, palonosetron did not inhibit the anti-tumour 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.
Palonosetron has been administered safely with analgesics, anti-emetic/anti-nauseants, antispasmodics and anti-cholinergic medicinal products.
There is no experience of palonosetron in human pregnancy, therefore, palonosetron should not be used in pregnant women. Since there is no data concerning excretion of palonosetron in breast milk, breast-feeding should be discontinued during therapy.
No studies on the effects on the ability to drive and use machines have been performed. Since palonosetron may include dizziness, somnolence or fatigue, patients should be cautioned when driving or operating machines.
In clinical studies at a dose of 250 micrograms (total 633 patients) the most frequently observed adverse reactions, at least possibly related to ONICIT, were headache (9%) and constipation (5%).
In the clinical studies the following adverse reactions were observed as possibly or probably related to ONICIT and are listed below according to the standard system organ class of MedDRA. These were classified as common (>1/100, <1/10) or uncommon (>1/1 000, <1/100).
Uncommon: Hyperkalaemia, metabolic disorders, hypocalcaemia, anorexia, hyperglycaemia, decreased appetite
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, upper abdominal pain, 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
Uncommon: Elevated transaminases, hypokalaemia, electrocardiogram QT prolonged
Very rare cases (<1/10 000) of hypersensitivity reactions and injection site reactions (burning, induration, discomfort and pain) were reported from post-marketing experience.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
