ALOXI Soft capsule Ref.[8703] Active ingredients: Palonosetron

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 QT corrected (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.

Aloxi contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicinal product. Aloxi capsules may also contain a trace of lecithin derived from soya. Therefore, patients with known hypersensitivity to peanut or soya, should be monitored closely for signs of an allergic reaction.

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 medicinal products

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 (see section 5.3). There is no experience of palonosetron in human pregnancy so palonosetron should not be used in pregnant women unless it is considered essential by the physician.

Breast-feeding

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

Fertility

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 at a dose of 500 micrograms (total 161 patients) the most frequently observed adverse reaction, at least possibly related to Aloxi, was headache (3.7%).

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).

Psychiatric disorders

Uncommon: Insomnia

Nervous system disorders

Common: Headache

Eye disorders

Uncommon: Eye swelling

Cardiac disorders

Uncommon: Atrioventricular block first degree, atrioventricular block second degree

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnoea

Gastrointestinal disorders

Uncommon: Constipation, nausea

Musculoskeletal and connective tissue disorders

Uncommon: Myalgia

Investigations

Uncommon: Blood bilirubin increased

In post marketing very rare cases (<1/10,000) of hypersensitivity reactions occurred with palonosetron solution for injection for intravenous use.

Reporting of suspected adverse reactions

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.

Not applicable.