Onicit 1ML / 5ML SOLUTION FOR INJECTION

Onicit 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.

Hypersensitivity to the active substance, palonosetron. Hypersensitivity to any excipients listed under u2018Compositionu2019.

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-HT 3 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.

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.

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.

Chemotherapeutic agents: In preclinical studies, palonosetron did not inhibit the anti-tumour 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. Other medicinal products: 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.

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, 1/1 000, <1/100).

Metabolism and nutrition disorders
Uncommon: Hyperkalaemia, metabolic disorders, hypocalcaemia, anorexia, hyperglycaemia, decreased appetite

Psychiatric disorders
Uncommon: Anxiety, euphoric mood

Nervous system disorders
Common: Headache, Dizziness
Uncommon: Somnolence, insomnia, paraesthesia, hypersomnia, peripheral sensory neuropathy

Eye disorders
Uncommon: Eye irritation, amblyopia

Ear and labyrinth disorders
Uncommon: Motion sickness, tinnitus

Cardiac disorders
Uncommon: Tachycardia, bradycardia, extrasystoles, myocardial ischaemia, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles

Vascular disorders
Uncommon: Hypotension, hypertension, vein discolouration, vein distended

Respiratory, thoracic and mediastinal disorders
Uncommon: Hiccups

Gastrointestinal disorders
Common: Constipation, Diarrhoea
Uncommon: Dyspepsia, abdominal pain, upper abdominal pain, dry mouth, flatulence

Hepato-biliary disorders
Uncommon: Hyperbilirubinaemia

Skin and subcutaneous tissue disorders
Uncommon: Dermatitis allergic, pruritic rash

Musculoskeletal and connective tissue disorders
Uncommon: Arthralgia

Renal and urinary disorders
Uncommon: Urinary retention, glycosuria

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

Investigations
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.

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 overdose with ONICIT, 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 ONICIT overdose.