Kemoprev Iv 250 μg Solution for injection or infusion

KEMOPREV IV 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. KEMOPREV IV should be injected over 30 seconds. Repeated dosing of KEMOPREV IV within a seven-day interval is not recommended. The efficacy of KEMOPREV IV 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.

Special populations

Elderly population

No dosage adjustment is necessary in the elderly.

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.

Hepatic impairment

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

Paediatric population

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

Method of administration

KEMOPREV IV is for intravenous use.

KEMOPREV IV is contraindicated in:

• Hypersensitivity to palonosetron hydrochloride or to any of the excipients in KEMOPREV IV listed in section 6.1.

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 c interval. A specific thorough QT/QT c study was conducted in healthy volunteers for definitive data demonstrating the effect of palonosetron on QT/QT c (see section 5.1). However, as for other 5-HT 3 -antagonists, caution should be exercised in the use of KEMOPREV IV 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, brady dysrhythmias, conduction disturbances and inpatients taking anti-dysrhythmias medicines or other medicine that lead to QT prolongation or electrolyte abnormalities. Hypokalaemia and hypomagnesemia should be corrected prior to 5-HT 3 -antagonist administration.

There have been reports of serotonin syndrome with the use of 5-HT 3 -antagonists either alone or in combination with other serotonergic medicine (including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised.

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

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 medicines

In preclinical studies, palonosetron did not inhibit the antitumour activity of the five chemotherapeutic medicines 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 medicines (e.g. SSRIs and SNRIs)

There have been reports of serotonin syndrome following concomitant use of 5-HT 3 antagonists and other serotonergic medicines (including SSRIs and SNRIs).

Other medicine

Palonosetron has been administered safely with analgesics, antiemetic/anti-nauseants, antispasmodics and anticholinergic medicine.

Pregnancy

There is no experience of KEMOPREV IV in human pregnancy. Therefore, palonosetron should not be used in pregnant women.

Breastfeeding

As there are no data concerning palonosetron excretion in breast milk, breastfeeding 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.

Summary of safety profile

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

Tabulated summary of adverse reactions

The table below shows all adverse drug reactions (ADRs) observed during clinical trials and postmarket spontaneous reports with palonosetron hydrochloride.

System Organ Class

Frequency

• Frequent
• Less Frequent

Immune system disorders

• Hypersensitivity, anaphylaxis, anaphylactic/anaphylactoid reactions and shock

Metabolism and nutrition disorders

• Hyperkalaemia, metabolic disorders, hypocalcaemia, hypokalaemia, anorexia, hyperglycaemia, appetite decreased

Psychiatric disorders

• Anxiety, euphoric mood

Nervous system disorders

• Headache
• Dizziness
• Somnolence, insomnia, paraesthesia, hypersomnia, peripheral sensory neuropathy

Eye disorders

• Eye irritation, amblyopia

Ear and labyrinth disorders

• Motion sickness, tinnitus

Cardiac disorders

• Tachycardia, bradycardia, extrasystoles, myocardial ischaemia, sinus tachycardia, sinus dysrhythmias, supraventricular extrasystoles

Vascular disorders

• Hypotension, hypertension, vein discolouration, vein distended

Respiratory, thoracic and mediastinal disorders

• Hiccups

Gastrointestinal disorders

• Constipation
• Diarrhoea
• Dyspepsia, abdominal pain, abdominal pain upper, dry mouth, flatulence

Hepatobiliary disorders

• Hyperbilirubinaemia

Skin and subcutaneous tissue disorders

• Dermatitis allergic, pruritic rash

Musculoskeletal and connective tissue disorders

• Arthralgia

Renal and urinary disorders

• Urinary retention, glycosuria

General disorders and administration site conditions

• Asthenia, pyrexia, fatigue, feeling hot, influenza like illness
• Injection site reaction*

Investigations

• Elevated transaminases-, electrocardiogram QT prolonged

* Includes the following: burning, induration, discomfort and pain

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 professionals are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

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 KEMOPREV IV, 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 KEMOPREV IV overdose.