Palonosetron 0,05 Mg Solution

PALONOSETRON FRESENIUS is indicated for:

• the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and
• the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

Posology

Use in adults

250 micrograms palonosetron, administered as a single intravenous bolus, approximately 30 minutes before the start of chemotherapy. PALONOSETRON FRESENIUS should be injected over 30 seconds. Repeated dosing of PALONOSETRON FRESENIUS within a seven-day interval is not recommended. The efficacy of palonosetron as in PALONOSETRON FRESENIUS 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.

Use in children and adolescents

Use in patients under 18 years of age is not recommended until further data becomes available.

Use in elderly

No dosage adjustment is necessary in the elderly.

Use in patients with renal impairment

No dosage adjustment is necessary for patients with impaired renal function. No data is available for patients with end stage renal disease undergoing haemodialysis.

Use in patients with hepatic impairment

No dosage adjustment is necessary for patients with impaired hepatic function.

Method of administration

For intravenous use. Single use only, any unused solution should be discarded. See section 6.6 for instructions for use.

• Hypersensitivity to palonosetron or to any of the excipients of PALONOSETRON FRESENIUS (see section 6.1).

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

Serotonin syndrome

There have been reports of serotonin syndrome with the use of 5-HT3 antagonists (such as PALONOSETRON FRESENIUS), either alone or in combination with other serotonergic medicines such as SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin noradrenaline reuptake inhibitors). Appropriate observation of patients for serotonin syndrome-like symptoms is advised.

Constipation/obstipation

PALONOSETRON FRESENIUS may increase large bowel transit time. Faecal impaction requiring hospitalisation have been reported in association with a dose of 750 u03bcg palonosetron as in PALONOSETRON FRESENIUS. Patients with a history of constipation or signs of sub-acute intestinal obstruction should be monitored following administration.

Cardiac effects

At all dose levels tested, palonosetron as in PALONOSETRON FRESENIUS did not induce clinically relevant prolongation of the QTc interval. However, as with other 5-HT3 antagonists, caution should be exercised in the concomitant use of PALONOSETRON FRESENIUS with medicines that increase the QT interval, or in patients who have, or are likely to develop, prolongation of the QT interval:

• with a personal or family history of QT prolongation,
• with bradydysrhythmia,
• with conduction disturbances,
• with electrolyte abnormalities,
• with congestive heart failure,
• taking medicines that increase the QT interval,
• taking anti-dysrhythmic medicines, or
• taking other medicines that lead to electrolyte abnormalities.

Hypokalaemia and hypomagnesemia should be corrected prior to PALONOSETRON FRESENIUS administration.

Palonosetron is mainly metabolised by CYP2D6, with minor contribution by CYP3A4 and CYP1A2 isoenzymes. Based on in vitro studies, palonosetron as in PALONOSETRON FRESENIUS does not inhibit or induce cytochrome P450 isoenzymes at clinically relevant concentrations.

Serotonergic medicines

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic medicines (including SSRIs and SNRIs).

Chemotherapeutic medicines

In pre-clinical studies, palonosetron as in PALONOSETRON FRESENIUS did not inhibit the anti-tumour activity of the five chemotherapeutic medicines tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C).

Metoclopramide

In a clinical study, no significant pharmacokinetic interaction has been demonstrated between 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.

Other medicines

Palonosetron as in PALONOSETRON FRESENIUS has been administered safely with analgesics, anti-emetic/anti-nauseants, antispasmodics and anticholinergic medicines.

Pregnancy

There is no experience of palonosetron in human pregnancy. PALONOSETRON FRESENIUS should therefore not be used in pregnant women.

Breastfeeding

Since there is no data concerning excretion of palonosetron in breastmilk, breastfeeding should be discontinued during therapy with PALONOSETRON FRESENIUS.

No studies on the effects on the ability to drive and use machines have been performed. Since palonosetron as in PALONOSETRON FRESENIUS may induce dizziness, somnolence or fatigue, patients should be cautioned when driving or operating machines.

Summary of the safety profile

In clinical studies at a dose of 250 micrograms the most frequently observed adverse reactions, at least possibly related to palonosetron as in PALONOSETRON FRESENIUS, were headache and constipation.

Tabulated list of adverse events

System organ class/ Adverse reactions Frequency

• Immune system disorders
• Less frequent: Hypersensitivity, anaphylaxis, anaphylactic/anaphylactoid reactions and shock

• Metabolism and nutrition disorders
• Less frequent: Hyperkalaemia, metabolic disorders, hypocalcaemia, hypokalaemia, anorexia, hyperglycaemia, decreased appetite

• Psychiatric disorders
• Less frequent: Anxiety, euphoric mood

• Nervous system disorders
• Frequent: Headache, dizziness
• Less frequent: Somnolence, insomnia, paraesthesia, hypersomnia, peripheral sensory neuropathy

• Eye disorders
• Less frequent: Eye irritation, amblyopia

• Ear and labyrinth disorders
• Less frequent: Motion sickness, tinnitus

• Cardiac disorders
• Less frequent: Tachycardia, bradycardia, extrasystoles, myocardial ischaemia, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles, electrocardiogram QT prolonged

• Vascular disorders
• Less frequent: Hypotension, hypertension, vein discolouration, vein distended

• Respiratory, thoracic and mediastinal disorders
• Less frequent: Hiccups

• Gastrointestinal disorders
• Frequent: Constipation, diarrhoea
• Less frequent: Dyspepsia, abdominal pain, upper abdominal pain, dry mouth, flatulence

• Hepato-biliary disorders
• Less frequent: Hyperbilirubinaemia, elevated transaminases

• Skin and subcutaneous tissue disorders
• Less frequent: Allergic dermatitis, pruritic rash

• Musculoskeletal and connective tissue disorders
• Less frequent: Arthralgia

• Renal and urinary disorders
• Less frequent: Urinary retention, glycosuria

• General disorders and administration site conditions
• Less frequent: Asthenia, pyrexia, fatigue, feeling hot, influenza like illness

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on the SAHPRA website. Healthcare providers are asked to report any suspected adverse drug reactions to the Holder of the Certificate of Registration at the following email address: [email protected] and to the relevant medicines' regulatory authority in the country where the product is marketed.

No case of overdose has been reported. Doses of up to 6 mg have been used in clinical trials. The highest dose group showed a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed.

In the unlikely event of an overdose with PALONOSETRON FRESENIUS, 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 palonosetron overdose.