Nocipal 250 μg/ 5 mL Solution for injection

NOCIPAL 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

Adults: A single, intravenous bolus dose of 250 u03bcg should be administered approximately 30 minutes prior to the start of chemotherapy. NOCIPAL should be injected over 30 seconds. Repeated dosing of NOCIPAL within a seven day interval is not recommended. The efficacy of NOCIPAL in the prevention of nausea and vomiting induced by highly emetogenic chemotherapy may be augmented by the addition of corticosteroid administered prior to chemotherapy.

Children and adolescents: NOCIPAL should not be used in patients under the age of 18.

Elderly: No dosage adjustment is required in the elderly (patients older than 65 years).

Use in patients with renal impairment: No dosage adjustment is required in patients with impaired renal function. Data is not available for haemodialysis patients with end stage renal disease.

Patients with hepatic impairment: No dosage adjustment is required in patients with impaired hepatic function.

Method of administration

For intravenous use only.

Hypersensitivity to palonosetron or any other ingredient of NOCIPAL listed in section 6.1.

Gastrointestinal effects: Patients with a history of constipation or signs of sub-acute intestinal obstruction should be monitored as palonosetron as in NOCIPAL may increase large bowel transit time. Cases of constipation with faecal impaction requiring hospitalisation have been reported in association with palonosetron 750 micrograms.

Cardiac effects: At the tested dose levels, palonosteron did not induce clinically relevant prolongation of the QTc interval. However, caution should be exercised when prescribing 5-HT3 receptor antagonists, including palonosetron as in NOCIPAL, with other medicines that prolong the QT interval or in patients who have or are likely to develop increased QT interval. These conditions included patients with a personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, bradydysrhythmias, conduction disturbances and in patients taking anti-dysrhythmic medicines or other medical 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.

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

Excipient information NOCIPAL contains less than 1 mmol sodium (23 mg) per vial, i.e essentially u201csodium freeu201d.

There have been reports of transient ECG changes in some patients taking 5-HT3 antagonists. As a result, there is a need for caution when NOCIPAL is given together with medicines that prolong 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.

Chemotherapeutic medicines: It has been reported that palonosetron as in NOCIPAL does not inhibit the anti-tumour activity of cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C.

Inducers and inhibitors of CYP2D6: Pharmacokinetics studies have shown that palonosetron as in NOCIPAL clearance is not significantly affected by co-administration with CYP2D6 inducers (such as dexamethasone and rifampicin) or inhibitors like amiodarone, celecoxib, chlorpromazine, cimetidine, doxorubicin, fluoxetine, haloperidol, paroxetine, quinidine, ranitidine, ritonavir, sertraline or terbinafine.

Co-administration of the CYP2D6 inhibitor metoclopramide (when administered orally) with a single intravenous dose of palonosetron as in NOCIPAL did not result in any significant pharmacokinetic interactions.

Serotonergic medicines (e.g. SSRIs and SNRIs) Serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic medicines (including SSRIs and SNRIs) may occur.

Others: NOCIPAL has been demonstrated to be safe for use with the following medicines:

• Corticosteroids
• Analgesics
• Other anti-emetics and anti-nauseants
• Antispasmodics
• Anti-cholinergics

Pregnancy: There is no experience of palonosetron as in NOCIPAL in human pregnancy, therefore, NOCIPAL should not be used in pregnant women.

Breastfeeding: There is no data concerning excretion of palonosetron 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. Palonosetron as in NOCIPAL may cause fatigue, dizziness or somnolence, patients should be cautioned about driving and using machines until they know how NOCIPAL affect them.

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

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

Psychiatric disorders: Less frequent: Anxiety, euphoria.

Nervous system disorders: Frequent: Headache, dizziness. Less frequent: somnolence, insomnia, paraesthesia, hypersomnia, peripheral sensory neuropathy, seizures.

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.

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.

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

Musculoskeletal, connective tissue and bone 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. Hypersensitivity reactions and injection site reactions (burning induration, discomfort and pain).

Investigations: Less frequent: Elevated transaminases, hypokalaemia, electrocardiogram QT prolonged.

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. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 or to Cipla at [email protected].

No known cases of overdose have been reported. Doses of up to 6 mg have been used in clinical trials. In the event of overdose with NOCIPAL, this should be managed with supportive care. Due to the large volume of distribution; dialysis is unlikely to be an effective treatment for NOCIPAL overdose.