Palonosetron

/ Teva Israel LTD, Israel

This medicinal product should be used only before chemotherapy administration. Please refer to the license holder for further details.

This medicinal product is indicated in adults and in paediatric patients 1 month of age and older for the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy, and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

Hypersensitive to palonosetron or to any of the excipients.

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.
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.
This drug should not be used to prevent or treat nausea and vomiting in the days following chemotherapy if not associated with another chemotherapy administration.

Common: Headache, dizziness, Constipation, diarrhea.
Pediatric population
Common: headache.
Please refer to the license holder for further details.

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.
Chemotherapeutic agents: In preclinical studies, palonosetron did not inhibit the antitumour activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C).
Metoclopramide: 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.
CYP2D6 inducers and inhibitors: 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).
Corticosteroids: Palonosetron has been administered safely with corticosteroids.
Serotonergic Drugs (e.g. SSRIs and SNRIs): There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).
Other medicinal products: Palonosetron has been administered safely with analgesics, antiemetic/antinauseants, antispasmodics and anticholinergic medicinal products.

Pregnancy: 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.
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.
Lactation: As there are no data concerning palonosetron excretion in breast milk, breast-feeding should be discontinued during therapy.

No case of overdose has been reported. Doses of up to 6 mg have been used in adult clinical studies. The highest dose group showed a similar incidence of adverse reactions compared to the other dose groups and no dose response effects were observed. In the unlikely event of overdose with this medical product, this should be managed with supportive care. Dialysis studies have not been performed, however, due to the large volume of distribution, dialysis is unlikely to be an effective treatment for this medical product overdose.